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Neuropsychiatric side effects of hormonal contraceptives: More common than you think!
Since its introduction in 1950, the combined oral contraceptive pill has been used by countless women as a method for birth control (Liao P. Can Fam Physician. 2012 Dec; 58[12]:e757-e760).
Hormonal contraception (HC) provides women with both contraceptive and noncontraceptive benefits, most notably a method for avoiding unintended pregnancy. In addition to being an effective method of contraception, oral contraceptive pills (OCPs) are well established for treating conditions such as hirsutism, pain symptoms associated with endometriosis and adenomyosis, and pelvic inflammatory disease, among others (Schindler A. Int J Endocrinol Metab. 2013 Winter;11[1]:41-7).
Combined hormonal contraceptives are also first-line treatment for women with menstrual disorders, and in women with polycystic ovary syndrome, can offer an effective long-term method to regulate their menstrual cycle, decrease androgens, clear up oily skin and acne, and reduce facial hair while also providing them with effective contraception (de Melo et al. Open Access J Contracept. 2017;8:13-23).
Associations between ‘the pill’ and mood effects remain controversial
More than 100 million women worldwide use hormonal contraceptives today, yet despite this, the data are mixed regarding the prevalence and extent of neuropsychiatric symptoms and mood changes associated with use of “the pill.” Some studies show combined oral contraceptives are associated with a decrease in general well-being, but had no effect on depression, in women compared with placebo (Zethraeus N et al. Fertil Steril. 2017 May;107[5]:1238-45).
However, a large Danish study published in JAMA Psychiatry of more than 1 million women found a significant association between use of hormonal contraception and antidepressant use or first diagnosis of depression, with adolescents having a higher rate of first depression diagnosis and antidepressant use compared with women 20–30 years old (Skovlund C et al. JAMA Psychiatry. 2016 Nov 1;73[11]:1154-62).
Studies have also shown long-term exposure to levonorgestrel is significantly associated with anxiety and sleep problems in women without a history of these issues (Slattery J et al. Drug Saf. 2018 Oct;41[10]:951-8). A recent small nationwide cohort study in France suggests this may also be true of levonorgestrel delivered by intrauterine devices (IUD) and the association may be dose-dependent (Roland N et al. JAMA. 2023;329[3]:257-9).
Of note, a study published in the American Journal of Psychiatry found a nearly twofold risk of suicide attempt and over threefold risk of suicide among women taking hormonal contraception compared with women who had never used hormonal contraceptives (Skovlund et al. Am J Psychiatry. 2017 Nov 17:appiajp201717060616).
Knowledge gaps make drawing conclusions difficult
The latest information on use of antidepressant and antianxiety medications in women of reproductive age (18-44 years) is sparse and, in some cases, outdated. According to data from the National Health and Nutrition Examination Survey, 18.6% of adult women 18 years or older reported using antidepressant medications within the last 30 days in 2017-2018, an increase from 13.8% in 2009-2010. Among women aged 15-44 year with private employer–sponsored insurance surveyed during 2008-2013, the results showed 15.4% of women filled a prescription for an antidepressant. We must look back further to find data on antianxiety medication use among women aged 18-44 years where use of antianxiety drugs (anxiolytics, sedatives, and hypnotics) was 4.3% between 2005 and 2008.
A lack of literature in this area is likely due to significant underreporting, and an inability to select patients who are sensitive to or at risk of developing neuropsychiatric symptoms resulting from hormonal contraception use because the true pathophysiology is unknown. Existing studies tend to use varying methods to assess mood changes, and do not usually specify hormonal contraceptive use type in their analyses (Schaffir J et al. Eur J Contracept Reprod Health Care. 2016 Oct;21[5]:347-55).
Studies of this nature also require large sample sizes, but the percentage of women who develop neuropsychiatric symptoms from hormonal contraceptive use has historically been relatively small. In the late 1990s, Rosenberg and colleagues found 46% of 1,657 women discontinued oral contraceptives due to side effects within 6 months of starting a new prescription; of these women, 5% reported mood changes as their reason for discontinuing oral contraceptives (Rosenberg M et al. Am J Obstet Gynecol. 1998 Sep;179[3 Pt 1]:577-82).
One might expect that, as lower dosage combined hormonal contraceptives were developed in the 1980s, that the rate of reporting psychological side effects would continue to decrease as well. Yet greater awareness of the potential for mood changes while on “the pill” as outlined by the lay press and social media may be leading to increased reporting of neuropsychiatric effects in women. In a recent cross-sectional survey of 188 women in New York, 43.6% said they experienced mood changes while on hormonal contraceptives, and 61.2% of women with histories of psychiatric illness reported mood changes they attributed to hormonal contraceptives (Martell S et al. Contracept Reprod Med. 2023;8:9).
Martell and colleagues found 48.3% of women cited side effects as a reason for discontinuing hormonal contraception, and 43 participants mentioned psychological side effects unprompted, including 2 patients with suicidal thoughts. The authors said this suggests “psychological side effects, at least in part, may have impacted” HC users’ decisions to switch from OCPs to an alternative method of contraception.
It is also not clear what risk factors exist for women who develop neuropsychiatric symptoms from hormonal contraceptive use. First, it is important to note that both progestin-only contraceptives and combined hormonal contraceptives are classified by the Centers for Disease Control and Prevention’s US Medical Eligibility Criteria for Contraceptive Use, 2016 as having no restrictions for use, including among patients with depression. While women in a smaller subgroup have significant neuropsychiatric symptoms related to their hormonal contraceptives, the underlying mechanism is unknown, and is thought to be largely related to the progestogen component of combined hormonal contraceptives or progestogen-only contraceptives (Mu E. Aust Prescr. 2022 Jun; 45[3]:75-9). We know that some women are hormone sensitive, while others are less so, and some not at all. Progestogens could affect mood as a direct action of the progestogen, because progestogens can be neurosteroids, or the progestogen effect could be mediated secondarily through a change in that woman’s own production of or bioavailability of androgens or naturally occurring estrogens (Giatti S. J Mol Endocrinol. 2016 Aug;57[2]:R109-26).
Here, we also find that currently available evidence limits our ability to draw firm conclusions. A study by Berry-Bibee and colleagues found a “low concern for clinically significant interactions” between hormonal contraception and psychotropic drugs, but was limited by quality/quantity of evidence (Berry-Bibee E et al. Contraception. 2016 Dec;94[6]:650-67). Interestingly, a study by Robinson and colleagues from the mid-2000s posited based on low evidence that “psychological response to the practice of contraception” was a potential explanation for the side effect profile of hormonal contraception (Robinson S et al. Med Hypotheses. 2004;63[2]:268-73).
Further, it may be that women with premenstrual dysphoric disorder (PMDD) might be selected for oral contraceptives, and they are predisposed to other neuropsychiatric problems. Estimates have placed the prevalence of comorbid psychiatric disorders such as anxiety, major depression, bipolar disorder, and posttraumatic stress disorder as high as 70% for women with PMDD (Sepede G et al. Neuropsychiatr Dis Treat. 2020;16:415-26). This phenomenon is not new, having been characterized in the lay literature nearly 20 years ago, by endocrinologist Geoffrey P. Redmond, MD (Redmond GP. The Hormonally Vulnerable Woman. New York: HarperCollins; 2005).
While the cause is not exactly idiosyncratic, They tend to have an entire spectrum of responses to the progestogens in combined or progestin-only contraceptives, ranging from just a flattened affect – which could easily be explained by their flattened level of endogenous hormones – to frank depression. Their frank depression, in turn, can be demonstrated to include suicidal ideation and actual suicide.
Compounding this issue is a woman’s perception of her sexuality. Some women with low sexual desire or sexual problems who are younger may have more distress about their problems compared with women of older reproductive age. While the reason for that is not clear, it may be that in the sexual arena, it is more important for some younger women to be a sexual person than in perimenopausal women, or that women who are younger are more likely to be partnered than women of older reproductive age. While the European Society of Sexual Medicine concluded in a 2019 position statement that there is inconclusive evidence whether hormonal contraception may be contributing to changes in sexual desire and sexual dysfunction, it appears that “a minority of women” experience “better or worse sexual functioning” from taking combined oral contraceptives (Both S et al. J Sex Med. 2019 Nov;16[11]:1681-95), suggesting that the majority of women report no significant changes.
Practitioners should discuss mood effects during consultation
An ob.gyn., primary care physicians, or others with prescriptive authority (i.e. nurse practitioners and physician assistants) in clinical practice may encounter a patient who seems to have mood side effects owing to progestogen-containing contraceptives that they prescribe. However, many ob.gyns. are likely unaware of the prevalence, or that some of those same patients can have such significant mood effects that they would become or are suicidal.
I believe questioning patients about mood effects during consultation and particularly during follow-up following the initiation of any hormonal contraceptive is worth a passing comment for every patient, which should include mood effects in broader discussion for anyone currently using an antidepressant, patients with a history of antidepressant use, and patients who have considered suicide. As we do with other drugs, these questions can be posed in the form of a questionnaire followed up by the practitioner in counseling.
Practitioners who encounter a patient with mood changes as a result of hormonal contraceptive use can consider changing to a nonhormonal method of birth control, or recommending the patient use a barrier method during sexual activity, as none of these options have neuropsychiatric side effects.
Ultimately, practitioners of all types need to engage in shared decision-making to identify the key benefits and risks of hormonal contraceptive use for each patient, which may involve trial and error to determine the ideal treatment. It is critical that practitioners of all types strike a balance between alleviating patient concerns about potential mood changes, monitoring patients with an appreciable risk of mood changes, and continuing patients on hormonal contraception for whom the benefits outweigh the risks.
Dr. Simon is a clinical professor at George Washington University and the medical director and founder of IntimMedicine Specialists in Washington, which provides patient-focused care for women across the reproductive life cycle. He is a past president of the International Society for the Study of Women’s Sexual Health and the North American Menopause Society. Dr. Simon has been a consultant to, received grant and research support from, and served on the speakers bureau for various pharmaceutical companies that develop combination hormonal contraceptives. Email Dr. Simon at [email protected].
Since its introduction in 1950, the combined oral contraceptive pill has been used by countless women as a method for birth control (Liao P. Can Fam Physician. 2012 Dec; 58[12]:e757-e760).
Hormonal contraception (HC) provides women with both contraceptive and noncontraceptive benefits, most notably a method for avoiding unintended pregnancy. In addition to being an effective method of contraception, oral contraceptive pills (OCPs) are well established for treating conditions such as hirsutism, pain symptoms associated with endometriosis and adenomyosis, and pelvic inflammatory disease, among others (Schindler A. Int J Endocrinol Metab. 2013 Winter;11[1]:41-7).
Combined hormonal contraceptives are also first-line treatment for women with menstrual disorders, and in women with polycystic ovary syndrome, can offer an effective long-term method to regulate their menstrual cycle, decrease androgens, clear up oily skin and acne, and reduce facial hair while also providing them with effective contraception (de Melo et al. Open Access J Contracept. 2017;8:13-23).
Associations between ‘the pill’ and mood effects remain controversial
More than 100 million women worldwide use hormonal contraceptives today, yet despite this, the data are mixed regarding the prevalence and extent of neuropsychiatric symptoms and mood changes associated with use of “the pill.” Some studies show combined oral contraceptives are associated with a decrease in general well-being, but had no effect on depression, in women compared with placebo (Zethraeus N et al. Fertil Steril. 2017 May;107[5]:1238-45).
However, a large Danish study published in JAMA Psychiatry of more than 1 million women found a significant association between use of hormonal contraception and antidepressant use or first diagnosis of depression, with adolescents having a higher rate of first depression diagnosis and antidepressant use compared with women 20–30 years old (Skovlund C et al. JAMA Psychiatry. 2016 Nov 1;73[11]:1154-62).
Studies have also shown long-term exposure to levonorgestrel is significantly associated with anxiety and sleep problems in women without a history of these issues (Slattery J et al. Drug Saf. 2018 Oct;41[10]:951-8). A recent small nationwide cohort study in France suggests this may also be true of levonorgestrel delivered by intrauterine devices (IUD) and the association may be dose-dependent (Roland N et al. JAMA. 2023;329[3]:257-9).
Of note, a study published in the American Journal of Psychiatry found a nearly twofold risk of suicide attempt and over threefold risk of suicide among women taking hormonal contraception compared with women who had never used hormonal contraceptives (Skovlund et al. Am J Psychiatry. 2017 Nov 17:appiajp201717060616).
Knowledge gaps make drawing conclusions difficult
The latest information on use of antidepressant and antianxiety medications in women of reproductive age (18-44 years) is sparse and, in some cases, outdated. According to data from the National Health and Nutrition Examination Survey, 18.6% of adult women 18 years or older reported using antidepressant medications within the last 30 days in 2017-2018, an increase from 13.8% in 2009-2010. Among women aged 15-44 year with private employer–sponsored insurance surveyed during 2008-2013, the results showed 15.4% of women filled a prescription for an antidepressant. We must look back further to find data on antianxiety medication use among women aged 18-44 years where use of antianxiety drugs (anxiolytics, sedatives, and hypnotics) was 4.3% between 2005 and 2008.
A lack of literature in this area is likely due to significant underreporting, and an inability to select patients who are sensitive to or at risk of developing neuropsychiatric symptoms resulting from hormonal contraception use because the true pathophysiology is unknown. Existing studies tend to use varying methods to assess mood changes, and do not usually specify hormonal contraceptive use type in their analyses (Schaffir J et al. Eur J Contracept Reprod Health Care. 2016 Oct;21[5]:347-55).
Studies of this nature also require large sample sizes, but the percentage of women who develop neuropsychiatric symptoms from hormonal contraceptive use has historically been relatively small. In the late 1990s, Rosenberg and colleagues found 46% of 1,657 women discontinued oral contraceptives due to side effects within 6 months of starting a new prescription; of these women, 5% reported mood changes as their reason for discontinuing oral contraceptives (Rosenberg M et al. Am J Obstet Gynecol. 1998 Sep;179[3 Pt 1]:577-82).
One might expect that, as lower dosage combined hormonal contraceptives were developed in the 1980s, that the rate of reporting psychological side effects would continue to decrease as well. Yet greater awareness of the potential for mood changes while on “the pill” as outlined by the lay press and social media may be leading to increased reporting of neuropsychiatric effects in women. In a recent cross-sectional survey of 188 women in New York, 43.6% said they experienced mood changes while on hormonal contraceptives, and 61.2% of women with histories of psychiatric illness reported mood changes they attributed to hormonal contraceptives (Martell S et al. Contracept Reprod Med. 2023;8:9).
Martell and colleagues found 48.3% of women cited side effects as a reason for discontinuing hormonal contraception, and 43 participants mentioned psychological side effects unprompted, including 2 patients with suicidal thoughts. The authors said this suggests “psychological side effects, at least in part, may have impacted” HC users’ decisions to switch from OCPs to an alternative method of contraception.
It is also not clear what risk factors exist for women who develop neuropsychiatric symptoms from hormonal contraceptive use. First, it is important to note that both progestin-only contraceptives and combined hormonal contraceptives are classified by the Centers for Disease Control and Prevention’s US Medical Eligibility Criteria for Contraceptive Use, 2016 as having no restrictions for use, including among patients with depression. While women in a smaller subgroup have significant neuropsychiatric symptoms related to their hormonal contraceptives, the underlying mechanism is unknown, and is thought to be largely related to the progestogen component of combined hormonal contraceptives or progestogen-only contraceptives (Mu E. Aust Prescr. 2022 Jun; 45[3]:75-9). We know that some women are hormone sensitive, while others are less so, and some not at all. Progestogens could affect mood as a direct action of the progestogen, because progestogens can be neurosteroids, or the progestogen effect could be mediated secondarily through a change in that woman’s own production of or bioavailability of androgens or naturally occurring estrogens (Giatti S. J Mol Endocrinol. 2016 Aug;57[2]:R109-26).
Here, we also find that currently available evidence limits our ability to draw firm conclusions. A study by Berry-Bibee and colleagues found a “low concern for clinically significant interactions” between hormonal contraception and psychotropic drugs, but was limited by quality/quantity of evidence (Berry-Bibee E et al. Contraception. 2016 Dec;94[6]:650-67). Interestingly, a study by Robinson and colleagues from the mid-2000s posited based on low evidence that “psychological response to the practice of contraception” was a potential explanation for the side effect profile of hormonal contraception (Robinson S et al. Med Hypotheses. 2004;63[2]:268-73).
Further, it may be that women with premenstrual dysphoric disorder (PMDD) might be selected for oral contraceptives, and they are predisposed to other neuropsychiatric problems. Estimates have placed the prevalence of comorbid psychiatric disorders such as anxiety, major depression, bipolar disorder, and posttraumatic stress disorder as high as 70% for women with PMDD (Sepede G et al. Neuropsychiatr Dis Treat. 2020;16:415-26). This phenomenon is not new, having been characterized in the lay literature nearly 20 years ago, by endocrinologist Geoffrey P. Redmond, MD (Redmond GP. The Hormonally Vulnerable Woman. New York: HarperCollins; 2005).
While the cause is not exactly idiosyncratic, They tend to have an entire spectrum of responses to the progestogens in combined or progestin-only contraceptives, ranging from just a flattened affect – which could easily be explained by their flattened level of endogenous hormones – to frank depression. Their frank depression, in turn, can be demonstrated to include suicidal ideation and actual suicide.
Compounding this issue is a woman’s perception of her sexuality. Some women with low sexual desire or sexual problems who are younger may have more distress about their problems compared with women of older reproductive age. While the reason for that is not clear, it may be that in the sexual arena, it is more important for some younger women to be a sexual person than in perimenopausal women, or that women who are younger are more likely to be partnered than women of older reproductive age. While the European Society of Sexual Medicine concluded in a 2019 position statement that there is inconclusive evidence whether hormonal contraception may be contributing to changes in sexual desire and sexual dysfunction, it appears that “a minority of women” experience “better or worse sexual functioning” from taking combined oral contraceptives (Both S et al. J Sex Med. 2019 Nov;16[11]:1681-95), suggesting that the majority of women report no significant changes.
Practitioners should discuss mood effects during consultation
An ob.gyn., primary care physicians, or others with prescriptive authority (i.e. nurse practitioners and physician assistants) in clinical practice may encounter a patient who seems to have mood side effects owing to progestogen-containing contraceptives that they prescribe. However, many ob.gyns. are likely unaware of the prevalence, or that some of those same patients can have such significant mood effects that they would become or are suicidal.
I believe questioning patients about mood effects during consultation and particularly during follow-up following the initiation of any hormonal contraceptive is worth a passing comment for every patient, which should include mood effects in broader discussion for anyone currently using an antidepressant, patients with a history of antidepressant use, and patients who have considered suicide. As we do with other drugs, these questions can be posed in the form of a questionnaire followed up by the practitioner in counseling.
Practitioners who encounter a patient with mood changes as a result of hormonal contraceptive use can consider changing to a nonhormonal method of birth control, or recommending the patient use a barrier method during sexual activity, as none of these options have neuropsychiatric side effects.
Ultimately, practitioners of all types need to engage in shared decision-making to identify the key benefits and risks of hormonal contraceptive use for each patient, which may involve trial and error to determine the ideal treatment. It is critical that practitioners of all types strike a balance between alleviating patient concerns about potential mood changes, monitoring patients with an appreciable risk of mood changes, and continuing patients on hormonal contraception for whom the benefits outweigh the risks.
Dr. Simon is a clinical professor at George Washington University and the medical director and founder of IntimMedicine Specialists in Washington, which provides patient-focused care for women across the reproductive life cycle. He is a past president of the International Society for the Study of Women’s Sexual Health and the North American Menopause Society. Dr. Simon has been a consultant to, received grant and research support from, and served on the speakers bureau for various pharmaceutical companies that develop combination hormonal contraceptives. Email Dr. Simon at [email protected].
Since its introduction in 1950, the combined oral contraceptive pill has been used by countless women as a method for birth control (Liao P. Can Fam Physician. 2012 Dec; 58[12]:e757-e760).
Hormonal contraception (HC) provides women with both contraceptive and noncontraceptive benefits, most notably a method for avoiding unintended pregnancy. In addition to being an effective method of contraception, oral contraceptive pills (OCPs) are well established for treating conditions such as hirsutism, pain symptoms associated with endometriosis and adenomyosis, and pelvic inflammatory disease, among others (Schindler A. Int J Endocrinol Metab. 2013 Winter;11[1]:41-7).
Combined hormonal contraceptives are also first-line treatment for women with menstrual disorders, and in women with polycystic ovary syndrome, can offer an effective long-term method to regulate their menstrual cycle, decrease androgens, clear up oily skin and acne, and reduce facial hair while also providing them with effective contraception (de Melo et al. Open Access J Contracept. 2017;8:13-23).
Associations between ‘the pill’ and mood effects remain controversial
More than 100 million women worldwide use hormonal contraceptives today, yet despite this, the data are mixed regarding the prevalence and extent of neuropsychiatric symptoms and mood changes associated with use of “the pill.” Some studies show combined oral contraceptives are associated with a decrease in general well-being, but had no effect on depression, in women compared with placebo (Zethraeus N et al. Fertil Steril. 2017 May;107[5]:1238-45).
However, a large Danish study published in JAMA Psychiatry of more than 1 million women found a significant association between use of hormonal contraception and antidepressant use or first diagnosis of depression, with adolescents having a higher rate of first depression diagnosis and antidepressant use compared with women 20–30 years old (Skovlund C et al. JAMA Psychiatry. 2016 Nov 1;73[11]:1154-62).
Studies have also shown long-term exposure to levonorgestrel is significantly associated with anxiety and sleep problems in women without a history of these issues (Slattery J et al. Drug Saf. 2018 Oct;41[10]:951-8). A recent small nationwide cohort study in France suggests this may also be true of levonorgestrel delivered by intrauterine devices (IUD) and the association may be dose-dependent (Roland N et al. JAMA. 2023;329[3]:257-9).
Of note, a study published in the American Journal of Psychiatry found a nearly twofold risk of suicide attempt and over threefold risk of suicide among women taking hormonal contraception compared with women who had never used hormonal contraceptives (Skovlund et al. Am J Psychiatry. 2017 Nov 17:appiajp201717060616).
Knowledge gaps make drawing conclusions difficult
The latest information on use of antidepressant and antianxiety medications in women of reproductive age (18-44 years) is sparse and, in some cases, outdated. According to data from the National Health and Nutrition Examination Survey, 18.6% of adult women 18 years or older reported using antidepressant medications within the last 30 days in 2017-2018, an increase from 13.8% in 2009-2010. Among women aged 15-44 year with private employer–sponsored insurance surveyed during 2008-2013, the results showed 15.4% of women filled a prescription for an antidepressant. We must look back further to find data on antianxiety medication use among women aged 18-44 years where use of antianxiety drugs (anxiolytics, sedatives, and hypnotics) was 4.3% between 2005 and 2008.
A lack of literature in this area is likely due to significant underreporting, and an inability to select patients who are sensitive to or at risk of developing neuropsychiatric symptoms resulting from hormonal contraception use because the true pathophysiology is unknown. Existing studies tend to use varying methods to assess mood changes, and do not usually specify hormonal contraceptive use type in their analyses (Schaffir J et al. Eur J Contracept Reprod Health Care. 2016 Oct;21[5]:347-55).
Studies of this nature also require large sample sizes, but the percentage of women who develop neuropsychiatric symptoms from hormonal contraceptive use has historically been relatively small. In the late 1990s, Rosenberg and colleagues found 46% of 1,657 women discontinued oral contraceptives due to side effects within 6 months of starting a new prescription; of these women, 5% reported mood changes as their reason for discontinuing oral contraceptives (Rosenberg M et al. Am J Obstet Gynecol. 1998 Sep;179[3 Pt 1]:577-82).
One might expect that, as lower dosage combined hormonal contraceptives were developed in the 1980s, that the rate of reporting psychological side effects would continue to decrease as well. Yet greater awareness of the potential for mood changes while on “the pill” as outlined by the lay press and social media may be leading to increased reporting of neuropsychiatric effects in women. In a recent cross-sectional survey of 188 women in New York, 43.6% said they experienced mood changes while on hormonal contraceptives, and 61.2% of women with histories of psychiatric illness reported mood changes they attributed to hormonal contraceptives (Martell S et al. Contracept Reprod Med. 2023;8:9).
Martell and colleagues found 48.3% of women cited side effects as a reason for discontinuing hormonal contraception, and 43 participants mentioned psychological side effects unprompted, including 2 patients with suicidal thoughts. The authors said this suggests “psychological side effects, at least in part, may have impacted” HC users’ decisions to switch from OCPs to an alternative method of contraception.
It is also not clear what risk factors exist for women who develop neuropsychiatric symptoms from hormonal contraceptive use. First, it is important to note that both progestin-only contraceptives and combined hormonal contraceptives are classified by the Centers for Disease Control and Prevention’s US Medical Eligibility Criteria for Contraceptive Use, 2016 as having no restrictions for use, including among patients with depression. While women in a smaller subgroup have significant neuropsychiatric symptoms related to their hormonal contraceptives, the underlying mechanism is unknown, and is thought to be largely related to the progestogen component of combined hormonal contraceptives or progestogen-only contraceptives (Mu E. Aust Prescr. 2022 Jun; 45[3]:75-9). We know that some women are hormone sensitive, while others are less so, and some not at all. Progestogens could affect mood as a direct action of the progestogen, because progestogens can be neurosteroids, or the progestogen effect could be mediated secondarily through a change in that woman’s own production of or bioavailability of androgens or naturally occurring estrogens (Giatti S. J Mol Endocrinol. 2016 Aug;57[2]:R109-26).
Here, we also find that currently available evidence limits our ability to draw firm conclusions. A study by Berry-Bibee and colleagues found a “low concern for clinically significant interactions” between hormonal contraception and psychotropic drugs, but was limited by quality/quantity of evidence (Berry-Bibee E et al. Contraception. 2016 Dec;94[6]:650-67). Interestingly, a study by Robinson and colleagues from the mid-2000s posited based on low evidence that “psychological response to the practice of contraception” was a potential explanation for the side effect profile of hormonal contraception (Robinson S et al. Med Hypotheses. 2004;63[2]:268-73).
Further, it may be that women with premenstrual dysphoric disorder (PMDD) might be selected for oral contraceptives, and they are predisposed to other neuropsychiatric problems. Estimates have placed the prevalence of comorbid psychiatric disorders such as anxiety, major depression, bipolar disorder, and posttraumatic stress disorder as high as 70% for women with PMDD (Sepede G et al. Neuropsychiatr Dis Treat. 2020;16:415-26). This phenomenon is not new, having been characterized in the lay literature nearly 20 years ago, by endocrinologist Geoffrey P. Redmond, MD (Redmond GP. The Hormonally Vulnerable Woman. New York: HarperCollins; 2005).
While the cause is not exactly idiosyncratic, They tend to have an entire spectrum of responses to the progestogens in combined or progestin-only contraceptives, ranging from just a flattened affect – which could easily be explained by their flattened level of endogenous hormones – to frank depression. Their frank depression, in turn, can be demonstrated to include suicidal ideation and actual suicide.
Compounding this issue is a woman’s perception of her sexuality. Some women with low sexual desire or sexual problems who are younger may have more distress about their problems compared with women of older reproductive age. While the reason for that is not clear, it may be that in the sexual arena, it is more important for some younger women to be a sexual person than in perimenopausal women, or that women who are younger are more likely to be partnered than women of older reproductive age. While the European Society of Sexual Medicine concluded in a 2019 position statement that there is inconclusive evidence whether hormonal contraception may be contributing to changes in sexual desire and sexual dysfunction, it appears that “a minority of women” experience “better or worse sexual functioning” from taking combined oral contraceptives (Both S et al. J Sex Med. 2019 Nov;16[11]:1681-95), suggesting that the majority of women report no significant changes.
Practitioners should discuss mood effects during consultation
An ob.gyn., primary care physicians, or others with prescriptive authority (i.e. nurse practitioners and physician assistants) in clinical practice may encounter a patient who seems to have mood side effects owing to progestogen-containing contraceptives that they prescribe. However, many ob.gyns. are likely unaware of the prevalence, or that some of those same patients can have such significant mood effects that they would become or are suicidal.
I believe questioning patients about mood effects during consultation and particularly during follow-up following the initiation of any hormonal contraceptive is worth a passing comment for every patient, which should include mood effects in broader discussion for anyone currently using an antidepressant, patients with a history of antidepressant use, and patients who have considered suicide. As we do with other drugs, these questions can be posed in the form of a questionnaire followed up by the practitioner in counseling.
Practitioners who encounter a patient with mood changes as a result of hormonal contraceptive use can consider changing to a nonhormonal method of birth control, or recommending the patient use a barrier method during sexual activity, as none of these options have neuropsychiatric side effects.
Ultimately, practitioners of all types need to engage in shared decision-making to identify the key benefits and risks of hormonal contraceptive use for each patient, which may involve trial and error to determine the ideal treatment. It is critical that practitioners of all types strike a balance between alleviating patient concerns about potential mood changes, monitoring patients with an appreciable risk of mood changes, and continuing patients on hormonal contraception for whom the benefits outweigh the risks.
Dr. Simon is a clinical professor at George Washington University and the medical director and founder of IntimMedicine Specialists in Washington, which provides patient-focused care for women across the reproductive life cycle. He is a past president of the International Society for the Study of Women’s Sexual Health and the North American Menopause Society. Dr. Simon has been a consultant to, received grant and research support from, and served on the speakers bureau for various pharmaceutical companies that develop combination hormonal contraceptives. Email Dr. Simon at [email protected].
Prostate cancer drug shortage leaves some with uncertainty
according to the Food and Drug Administration.
The therapy lutetium Lu 177 vipivotide tetraxetan (Pluvicto), approved in March 2022, will remain in limited supply until the drug’s manufacturer, Novartis, can ramp up production of the drug over the next 12 months.
In a letter in February, Novartis said it is giving priority to patients who have already started the regimen so they can “appropriately complete their course of therapy.” The manufacturer will not be taking any orders for new patients over the next 4-6 months, as they work to increase supply.
“We are operating our production site at full capacity to treat as many patients as possible, as quickly as possible,” Novartis said. “However, with a nuclear medicine like Pluvicto, there is no backup supply that we can draw from when we experience a delay.”
Pluvicto is currently made in small batches in the company’s manufacturing facility in Italy. The drug only has a 5-day window to reach its intended patient, after which time it cannot be used. Any disruption in the production or shipping process can create a delay.
Novartis said the facility in Italy is currently operating at full capacity and the company is “working to increase production capacity and supply” of the drug over the next 12 months at two new manufacturing sites in the United States.
The company also encountered supply problems with Pluvicto in 2022 after quality issues were discovered in the manufacturing process.
Currently, patients who are waiting for their first dose of Pluvicto will need to be rescheduled. The manufacturer will be reaching out to health care professionals with options for rescheduling.
Jonathan McConathy, MD, PhD, told The Wall Street Journal that “people will die from this shortage, for sure.”
Dr. McConathy, a radiologist at the University of Alabama at Birmingham who has consulted for Novartis, explained that some patients who would have benefited from the drug likely won’t receive it in time.
A version of this article first appeared on Medscape.com.
according to the Food and Drug Administration.
The therapy lutetium Lu 177 vipivotide tetraxetan (Pluvicto), approved in March 2022, will remain in limited supply until the drug’s manufacturer, Novartis, can ramp up production of the drug over the next 12 months.
In a letter in February, Novartis said it is giving priority to patients who have already started the regimen so they can “appropriately complete their course of therapy.” The manufacturer will not be taking any orders for new patients over the next 4-6 months, as they work to increase supply.
“We are operating our production site at full capacity to treat as many patients as possible, as quickly as possible,” Novartis said. “However, with a nuclear medicine like Pluvicto, there is no backup supply that we can draw from when we experience a delay.”
Pluvicto is currently made in small batches in the company’s manufacturing facility in Italy. The drug only has a 5-day window to reach its intended patient, after which time it cannot be used. Any disruption in the production or shipping process can create a delay.
Novartis said the facility in Italy is currently operating at full capacity and the company is “working to increase production capacity and supply” of the drug over the next 12 months at two new manufacturing sites in the United States.
The company also encountered supply problems with Pluvicto in 2022 after quality issues were discovered in the manufacturing process.
Currently, patients who are waiting for their first dose of Pluvicto will need to be rescheduled. The manufacturer will be reaching out to health care professionals with options for rescheduling.
Jonathan McConathy, MD, PhD, told The Wall Street Journal that “people will die from this shortage, for sure.”
Dr. McConathy, a radiologist at the University of Alabama at Birmingham who has consulted for Novartis, explained that some patients who would have benefited from the drug likely won’t receive it in time.
A version of this article first appeared on Medscape.com.
according to the Food and Drug Administration.
The therapy lutetium Lu 177 vipivotide tetraxetan (Pluvicto), approved in March 2022, will remain in limited supply until the drug’s manufacturer, Novartis, can ramp up production of the drug over the next 12 months.
In a letter in February, Novartis said it is giving priority to patients who have already started the regimen so they can “appropriately complete their course of therapy.” The manufacturer will not be taking any orders for new patients over the next 4-6 months, as they work to increase supply.
“We are operating our production site at full capacity to treat as many patients as possible, as quickly as possible,” Novartis said. “However, with a nuclear medicine like Pluvicto, there is no backup supply that we can draw from when we experience a delay.”
Pluvicto is currently made in small batches in the company’s manufacturing facility in Italy. The drug only has a 5-day window to reach its intended patient, after which time it cannot be used. Any disruption in the production or shipping process can create a delay.
Novartis said the facility in Italy is currently operating at full capacity and the company is “working to increase production capacity and supply” of the drug over the next 12 months at two new manufacturing sites in the United States.
The company also encountered supply problems with Pluvicto in 2022 after quality issues were discovered in the manufacturing process.
Currently, patients who are waiting for their first dose of Pluvicto will need to be rescheduled. The manufacturer will be reaching out to health care professionals with options for rescheduling.
Jonathan McConathy, MD, PhD, told The Wall Street Journal that “people will die from this shortage, for sure.”
Dr. McConathy, a radiologist at the University of Alabama at Birmingham who has consulted for Novartis, explained that some patients who would have benefited from the drug likely won’t receive it in time.
A version of this article first appeared on Medscape.com.
EPA seeks to limit ‘forever’ chemicals in U.S. drinking water
The Environmental Protection Agency is proposing a new rule that would greatly limit the concentration of endocrine-disrupting “forever” chemicals in drinking water.
The EPA on Tuesday announced the proposed National Primary Drinking Water Regulation (NPDWR) for six polyfluoroalkyl substances, more commonly known as PFAS, which are human-made chemicals used as oil and water repellents and coatings for common products including cookware, carpets, and textiles. Such substances are also widely used in cosmetics and food packaging.
The Endocrine Society, which represents more than 18,000 doctors who treat hormone disorders, says it fully supports the new EPA proposal. It explains that these substances, also known as endocrine-disrupting chemicals, “do not break down when they are released into the environment, and they continue to accumulate over time. They pose health dangers at incredibly low levels and have been linked to endocrine disorders such as cancer, thyroid disruption, and reproductive difficulties.”
“This is the first time the government has regulated a new chemical in drinking water in more than 30 years,” the society notes, adding, this “will require major water treatment upgrades at utilities across the country.”
Robert F. Powelson, president and CEO of the National Association of Water Companies, says addressing the PFAS in the nation’s water supply will cost “billions of dollars.”
“It’s a burden that under the current structure will disproportionately fall on water and wastewater customers in small communities and low-income families,” Mr. Powelson says in a statement. He says the onus should instead fall on “the polluters” – those who manufacture and use PFAS chemicals, who “should be held directly responsible for the clean-up costs.”
Although the EPA is proposing a health-based maximum contaminant level goal of zero for these chemicals in drinking water, it acknowledges that this is unenforceable and so has set what it considers an enforceable level, or maximum contaminant level (MCL), of 4 parts per trillion for two of the PFAS, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS).
A different standard has been proposed for the remaining four chemicals: perfluorononanoic acid (PFNA) and hexafluoropropylene oxide dimer acid (HFPO-DA) – known together as GenX chemicals – perfluorohexane sulfonic acid (PFHxS), and perfluorobutane sulfonic acid (PFBS).
Officials from the EPA told The Washington Post that these proposed limits would be as strong or stronger than limits from about a dozen states that have set their own drinking water standards in recent years.
“The experts here felt this was the level of stringency required to protect public health, and that the law would allow for us,” EPA Administrator Michael Regan told the newspaper. “This is a transformative action that we’re taking.”
The EPA is requesting public comment on the proposed regulation and will hold a public hearing on May 4, which members of the public can register to attend and comment on the rule proposal. The last day to register is April 28.
The EPA wants to finalize regulation by the end of 2023, although delays are common on new rules.
If it is fully implemented, “the rule will prevent thousands of deaths and reduce tens of thousands of serious PFAS-attributable illnesses,” the EPA statement says.
A version of this article first appeared on Medscape.com.
The Environmental Protection Agency is proposing a new rule that would greatly limit the concentration of endocrine-disrupting “forever” chemicals in drinking water.
The EPA on Tuesday announced the proposed National Primary Drinking Water Regulation (NPDWR) for six polyfluoroalkyl substances, more commonly known as PFAS, which are human-made chemicals used as oil and water repellents and coatings for common products including cookware, carpets, and textiles. Such substances are also widely used in cosmetics and food packaging.
The Endocrine Society, which represents more than 18,000 doctors who treat hormone disorders, says it fully supports the new EPA proposal. It explains that these substances, also known as endocrine-disrupting chemicals, “do not break down when they are released into the environment, and they continue to accumulate over time. They pose health dangers at incredibly low levels and have been linked to endocrine disorders such as cancer, thyroid disruption, and reproductive difficulties.”
“This is the first time the government has regulated a new chemical in drinking water in more than 30 years,” the society notes, adding, this “will require major water treatment upgrades at utilities across the country.”
Robert F. Powelson, president and CEO of the National Association of Water Companies, says addressing the PFAS in the nation’s water supply will cost “billions of dollars.”
“It’s a burden that under the current structure will disproportionately fall on water and wastewater customers in small communities and low-income families,” Mr. Powelson says in a statement. He says the onus should instead fall on “the polluters” – those who manufacture and use PFAS chemicals, who “should be held directly responsible for the clean-up costs.”
Although the EPA is proposing a health-based maximum contaminant level goal of zero for these chemicals in drinking water, it acknowledges that this is unenforceable and so has set what it considers an enforceable level, or maximum contaminant level (MCL), of 4 parts per trillion for two of the PFAS, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS).
A different standard has been proposed for the remaining four chemicals: perfluorononanoic acid (PFNA) and hexafluoropropylene oxide dimer acid (HFPO-DA) – known together as GenX chemicals – perfluorohexane sulfonic acid (PFHxS), and perfluorobutane sulfonic acid (PFBS).
Officials from the EPA told The Washington Post that these proposed limits would be as strong or stronger than limits from about a dozen states that have set their own drinking water standards in recent years.
“The experts here felt this was the level of stringency required to protect public health, and that the law would allow for us,” EPA Administrator Michael Regan told the newspaper. “This is a transformative action that we’re taking.”
The EPA is requesting public comment on the proposed regulation and will hold a public hearing on May 4, which members of the public can register to attend and comment on the rule proposal. The last day to register is April 28.
The EPA wants to finalize regulation by the end of 2023, although delays are common on new rules.
If it is fully implemented, “the rule will prevent thousands of deaths and reduce tens of thousands of serious PFAS-attributable illnesses,” the EPA statement says.
A version of this article first appeared on Medscape.com.
The Environmental Protection Agency is proposing a new rule that would greatly limit the concentration of endocrine-disrupting “forever” chemicals in drinking water.
The EPA on Tuesday announced the proposed National Primary Drinking Water Regulation (NPDWR) for six polyfluoroalkyl substances, more commonly known as PFAS, which are human-made chemicals used as oil and water repellents and coatings for common products including cookware, carpets, and textiles. Such substances are also widely used in cosmetics and food packaging.
The Endocrine Society, which represents more than 18,000 doctors who treat hormone disorders, says it fully supports the new EPA proposal. It explains that these substances, also known as endocrine-disrupting chemicals, “do not break down when they are released into the environment, and they continue to accumulate over time. They pose health dangers at incredibly low levels and have been linked to endocrine disorders such as cancer, thyroid disruption, and reproductive difficulties.”
“This is the first time the government has regulated a new chemical in drinking water in more than 30 years,” the society notes, adding, this “will require major water treatment upgrades at utilities across the country.”
Robert F. Powelson, president and CEO of the National Association of Water Companies, says addressing the PFAS in the nation’s water supply will cost “billions of dollars.”
“It’s a burden that under the current structure will disproportionately fall on water and wastewater customers in small communities and low-income families,” Mr. Powelson says in a statement. He says the onus should instead fall on “the polluters” – those who manufacture and use PFAS chemicals, who “should be held directly responsible for the clean-up costs.”
Although the EPA is proposing a health-based maximum contaminant level goal of zero for these chemicals in drinking water, it acknowledges that this is unenforceable and so has set what it considers an enforceable level, or maximum contaminant level (MCL), of 4 parts per trillion for two of the PFAS, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS).
A different standard has been proposed for the remaining four chemicals: perfluorononanoic acid (PFNA) and hexafluoropropylene oxide dimer acid (HFPO-DA) – known together as GenX chemicals – perfluorohexane sulfonic acid (PFHxS), and perfluorobutane sulfonic acid (PFBS).
Officials from the EPA told The Washington Post that these proposed limits would be as strong or stronger than limits from about a dozen states that have set their own drinking water standards in recent years.
“The experts here felt this was the level of stringency required to protect public health, and that the law would allow for us,” EPA Administrator Michael Regan told the newspaper. “This is a transformative action that we’re taking.”
The EPA is requesting public comment on the proposed regulation and will hold a public hearing on May 4, which members of the public can register to attend and comment on the rule proposal. The last day to register is April 28.
The EPA wants to finalize regulation by the end of 2023, although delays are common on new rules.
If it is fully implemented, “the rule will prevent thousands of deaths and reduce tens of thousands of serious PFAS-attributable illnesses,” the EPA statement says.
A version of this article first appeared on Medscape.com.
Toxic chemicals we consume without knowing it
Life expectancy is falling precipitously. Three-fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.
Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.
Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.
Microplastics
“Microplastics” is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.
Plastic waste is accumulating at alarming and devastating proportions – by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.
Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.
According to Tasha Stoiber, a senior scientist at the Environmental Working Group, “Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water.” The EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.
Pressure also is mounting for a ban on microbeads in personal care products.
Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.
Phthalates
Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (for example, flooring, shower curtains) and fragrances, air fresheners, and perfumes.
Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.
To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children’s toys), which are identifiable by the recycle code number 3, as well as air fresheners and fragranced products.
The EWG’s Skin Deep database provides an important resource on phthalate-free personal care products.
Despite pressure from consumer advocacy groups, the U.S. Food and Drug Administration has not yet banned phthalates in food packaging.
Bisphenol A (BPA)
BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.
Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.
As with phthalates, the majority of ingestion is thought to be food related. BPA has been found in more than 90% of a representative study population in the United States.
Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverages should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas and condensed soups. If canned products are bought, they should ideally be BPA free.
Dioxins and polychlorinated biphenyls (PCBs)
Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.
Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.
Notably, dioxin emissions have been reduced by 90% since the 1980s, and the U.S. Environmental Protection Agency has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.
The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the U.S. diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.
Pesticides
The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the U.S. population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.
Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.
A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE – a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer’s-type dementia as well as overall cognitive decline.
Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.
Per- and polyfluoroalkyl substances (PFAS)
PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as “forever chemicals.”
PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birth weight, and hormonal disruption.
The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS – a family of thousands of synthetic compounds – remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.
Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.
To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as “water resistant,” “stain-resistant,” and “nonstick.”
In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as “hazardous substances.”
Dr. Goel, clinical assistant professor of medicine at Weill Cornell Medicine, New York, has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.
Life expectancy is falling precipitously. Three-fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.
Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.
Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.
Microplastics
“Microplastics” is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.
Plastic waste is accumulating at alarming and devastating proportions – by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.
Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.
According to Tasha Stoiber, a senior scientist at the Environmental Working Group, “Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water.” The EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.
Pressure also is mounting for a ban on microbeads in personal care products.
Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.
Phthalates
Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (for example, flooring, shower curtains) and fragrances, air fresheners, and perfumes.
Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.
To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children’s toys), which are identifiable by the recycle code number 3, as well as air fresheners and fragranced products.
The EWG’s Skin Deep database provides an important resource on phthalate-free personal care products.
Despite pressure from consumer advocacy groups, the U.S. Food and Drug Administration has not yet banned phthalates in food packaging.
Bisphenol A (BPA)
BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.
Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.
As with phthalates, the majority of ingestion is thought to be food related. BPA has been found in more than 90% of a representative study population in the United States.
Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverages should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas and condensed soups. If canned products are bought, they should ideally be BPA free.
Dioxins and polychlorinated biphenyls (PCBs)
Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.
Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.
Notably, dioxin emissions have been reduced by 90% since the 1980s, and the U.S. Environmental Protection Agency has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.
The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the U.S. diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.
Pesticides
The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the U.S. population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.
Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.
A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE – a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer’s-type dementia as well as overall cognitive decline.
Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.
Per- and polyfluoroalkyl substances (PFAS)
PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as “forever chemicals.”
PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birth weight, and hormonal disruption.
The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS – a family of thousands of synthetic compounds – remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.
Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.
To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as “water resistant,” “stain-resistant,” and “nonstick.”
In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as “hazardous substances.”
Dr. Goel, clinical assistant professor of medicine at Weill Cornell Medicine, New York, has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.
Life expectancy is falling precipitously. Three-fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.
Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.
Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.
Microplastics
“Microplastics” is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.
Plastic waste is accumulating at alarming and devastating proportions – by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.
Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.
According to Tasha Stoiber, a senior scientist at the Environmental Working Group, “Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water.” The EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.
Pressure also is mounting for a ban on microbeads in personal care products.
Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.
Phthalates
Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (for example, flooring, shower curtains) and fragrances, air fresheners, and perfumes.
Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.
To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children’s toys), which are identifiable by the recycle code number 3, as well as air fresheners and fragranced products.
The EWG’s Skin Deep database provides an important resource on phthalate-free personal care products.
Despite pressure from consumer advocacy groups, the U.S. Food and Drug Administration has not yet banned phthalates in food packaging.
Bisphenol A (BPA)
BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.
Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.
As with phthalates, the majority of ingestion is thought to be food related. BPA has been found in more than 90% of a representative study population in the United States.
Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverages should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas and condensed soups. If canned products are bought, they should ideally be BPA free.
Dioxins and polychlorinated biphenyls (PCBs)
Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.
Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.
Notably, dioxin emissions have been reduced by 90% since the 1980s, and the U.S. Environmental Protection Agency has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.
The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the U.S. diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.
Pesticides
The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the U.S. population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.
Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.
A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE – a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer’s-type dementia as well as overall cognitive decline.
Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.
Per- and polyfluoroalkyl substances (PFAS)
PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as “forever chemicals.”
PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birth weight, and hormonal disruption.
The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS – a family of thousands of synthetic compounds – remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.
Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.
To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as “water resistant,” “stain-resistant,” and “nonstick.”
In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as “hazardous substances.”
Dr. Goel, clinical assistant professor of medicine at Weill Cornell Medicine, New York, has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.
Doctors are disappearing from emergency departments as hospitals look to cut costs
She didn’t know much about miscarriage, but this seemed like one.
In the emergency department, she was examined then sent home, she said. She went back when her cramping became excruciating. Then home again. It ultimately took three trips to the ED on 3 consecutive days, generating three separate bills, before she saw a doctor who looked at her blood work and confirmed her fears.
“At the time I wasn’t thinking, ‘Oh, I need to see a doctor,’ ” Ms. Valle recalled. “But when you think about it, it’s like, ‘Well, dang – why didn’t I see a doctor?’ ” It’s unclear whether the repeat visits were due to delays in seeing a physician, but the experience worried her. And she’s still paying the bills.
The hospital declined to discuss Ms. Valle’s care, citing patient privacy. But 17 months before her 3-day ordeal, Tennova had outsourced its emergency departments to American Physician Partners, a medical staffing company owned by private equity investors. APP employs fewer doctors in its EDs as one of its cost-saving initiatives to increase earnings, according to a confidential company document obtained by KHN and NPR.
This staffing strategy has permeated hospitals, and particularly emergency departments, that seek to reduce their top expense: physician labor. While diagnosing and treating patients was once their domain, doctors are increasingly being replaced by nurse practitioners and physician assistants, collectively known as “midlevel practitioners,” who can perform many of the same duties and generate much of the same revenue for less than half of the pay.
“APP has numerous cost saving initiatives underway as part of the Company’s continual focus on cost optimization,” the document says, including a “shift of staffing” between doctors and midlevel practitioners.
In a statement to KHN, American Physician Partners said this strategy is a way to ensure all EDs remain fully staffed, calling it a “blended model” that allows doctors, nurse practitioners, and physician assistants “to provide care to their fullest potential.”
Critics of this strategy say the quest to save money results in treatment meted out by someone with far less training than a physician, leaving patients vulnerable to misdiagnoses, higher medical bills, and inadequate care. And these fears are bolstered by evidence that suggests dropping doctors from EDs may not be good for patients.
A working paper, published in October by the National Bureau of Economic Research, analyzed roughly 1.1 million visits to 44 EDs throughout the Veterans Health Administration, where nurse practitioners can treat patients without oversight from doctors.
Researchers found that treatment by a nurse practitioner resulted on average in a 7% increase in cost of care and an 11% increase in length of stay, extending patients’ time in the ED by minutes for minor visits and hours for longer ones. These gaps widened among patients with more severe diagnoses, the study said, but could be somewhat mitigated by nurse practitioners with more experience.
The study also found that ED patients treated by a nurse practitioner were 20% more likely to be readmitted to the hospital for a preventable reason within 30 days, although the overall risk of readmission remained very small.
Yiqun Chen, PhD, who is an assistant professor of economics at the University of Illinois at Chicago and coauthored the study, said these findings are not an indictment of nurse practitioners in the ED. Instead, she said, she hopes the study will guide how to best deploy nurse practitioners: in treatment of simpler patients or circumstances when no doctor is available.
“It’s not just a simple question of if we can substitute physicians with nurse practitioners or not,” Dr. Chen said. “It depends on how we use them. If we just use them as independent providers, especially ... for relatively complicated patients, it doesn’t seem to be a very good use.”
Dr. Chen’s research echoes smaller studies, like one from The Harvey L. Neiman Health Policy Institute that found nonphysician practitioners in EDs were associated with a 5.3% increase in imaging, which could unnecessarily increase bills for patients. Separately, a study at the Hattiesburg Clinic in Mississippi found that midlevel practitioners in primary care – not in the emergency department – increased the out-of-pocket costs to patients while also leading to worse performance on 9 of 10 quality-of-care metrics, including cancer screenings and vaccination rates.
But definitive evidence remains elusive that replacing ER doctors with nonphysicians has a negative impact on patients, said Cameron Gettel, MD, an assistant professor of emergency medicine at Yale University, New Haven, Conn. Private equity investment and the use of midlevel practitioners rose in lockstep in the ED, Dr. Gettel said, and in the absence of game-changing research, the pattern will likely continue.
“Worse patient outcomes haven’t really been shown across the board,” he said. “And I think until that is shown, then they will continue to play an increasing role.”
For private equity, dropping ED docs is a “simple equation”
Private equity companies pool money from wealthy investors to buy their way into various industries, often slashing spending and seeking to flip businesses in 3 to 7 years. While this business model is a proven moneymaker on Wall Street, it raises concerns in health care, where critics worry the pressure to turn big profits will influence life-or-death decisions that were once left solely to medical professionals.
Nearly $1 trillion in private equity funds have gone into almost 8,000 health care transactions over the past decade, according to industry tracker PitchBook, including buying into medical staffing companies that many hospitals hire to manage their emergency departments.
Two firms dominate the ED staffing industry: TeamHealth, bought by private equity firm Blackstone in 2016, and Envision Healthcare, bought by KKR in 2018. Trying to undercut these staffing giants is American Physician Partners, a rapidly expanding company that runs EDs in at least 17 states and is 50% owned by private equity firm BBH Capital Partners.
These staffing companies have been among the most aggressive in replacing doctors to cut costs, said Robert McNamara, MD, a founder of the American Academy of Emergency Medicine and chair of emergency medicine at Temple University, Philadelphia.
“It’s a relatively simple equation,” Dr. McNamara said. “Their No. 1 expense is the board-certified emergency physician. So they are going to want to keep that expense as low as possible.”
Not everyone sees the trend of private equity in ED staffing in a negative light. Jennifer Orozco, president of the American Academy of Physician Associates, which represents physician assistants, said even if the change – to use more nonphysician providers – is driven by the staffing firms’ desire to make more money, patients are still well served by a team approach that includes nurse practitioners and physician assistants.
“Though I see that shift, it’s not about profits at the end of the day,” Ms. Orozco said. “It’s about the patient.”
The “shift” is nearly invisible to patients because hospitals rarely promote branding from their ED staffing firms and there is little public documentation of private equity investments.
Arthur Smolensky, MD, a Tennessee emergency medicine specialist attempting to measure private equity’s intrusion into EDs, said his review of hospital job postings and employment contracts in 14 major metropolitan areas found that 43% of ED patients were seen in EDs staffed by companies with nonphysician owners, nearly all of whom are private equity investors.
Dr. Smolensky hopes to publish his full study, expanding to 55 metro areas, later this year. But this research will merely quantify what many doctors already know: The ED has changed. Demoralized by an increased focus on profit, and wary of a looming surplus of emergency medicine residents because there are fewer jobs to fill, many experienced doctors are leaving the ED on their own, he said.
“Most of us didn’t go into medicine to supervise an army of people that are not as well trained as we are,” Dr. Smolensky said. “We want to take care of patients.”
“I guess we’re the first guinea pigs for our ER”
Joshua Allen, a nurse practitioner at a small Kentucky hospital, snaked a rubber hose through a rack of pork ribs to practice inserting a chest tube to fix a collapsed lung.
It was 2020, and American Physician Partners was restructuring the ED where Mr. Allen worked, reducing shifts from two doctors to one. Once Mr. Allen had placed 10 tubes under a doctor’s supervision, he would be allowed to do it on his own.
“I guess we’re the first guinea pigs for our ER,” he said. “If we do have a major trauma and multiple victims come in, there’s only one doctor there. ... We need to be prepared.”
Mr. Allen is one of many midlevel practitioners finding work in emergency departments. Nurse practitioners and physician assistants are among the fastest-growing occupations in the nation, according to the U.S. Bureau of Labor Statistics.
Generally, they have master’s degrees and receive several years of specialized schooling but have significantly less training than doctors. Many are permitted to diagnose patients and prescribe medication with little or no supervision from a doctor, although limitations vary by state.
The Neiman Institute found that the share of ED visits in which a midlevel practitioner was the main clinician increased by more than 172% between 2005 and 2020. Another study, in the Journal of Emergency Medicine, reported that if trends continue there may be equal numbers of midlevel practitioners and doctors in EDs by 2030.
There is little mystery as to why. Federal data shows emergency medicine doctors are paid about $310,000 a year on average, while nurse practitioners and physician assistants earn less than $120,000. Generally, hospitals can bill for care by a midlevel practitioner at 85% the rate of a doctor while paying them less than half as much.
Private equity can make millions in the gap.
For example, Envision once encouraged EDs to employ “the least expensive resource” and treat up to 35% of patients with midlevel practitioners, according to a 2017 PowerPoint presentation. The presentation drew scorn on social media and disappeared from Envision’s website.
Envision declined a request for a phone interview. In a written statement to KHN, spokesperson Aliese Polk said the company does not direct its physician leaders on how to care for patients and called the presentation a “concept guide” that does not represent current views.
American Physician Partners touted roughly the same staffing strategy in 2021 in response to the No Surprises Act, which threatened the company’s profits by outlawing surprise medical bills. In its confidential pitch to lenders, the company estimated it could cut almost $6 million by shifting more staffing from physicians to midlevel practitioners.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
She didn’t know much about miscarriage, but this seemed like one.
In the emergency department, she was examined then sent home, she said. She went back when her cramping became excruciating. Then home again. It ultimately took three trips to the ED on 3 consecutive days, generating three separate bills, before she saw a doctor who looked at her blood work and confirmed her fears.
“At the time I wasn’t thinking, ‘Oh, I need to see a doctor,’ ” Ms. Valle recalled. “But when you think about it, it’s like, ‘Well, dang – why didn’t I see a doctor?’ ” It’s unclear whether the repeat visits were due to delays in seeing a physician, but the experience worried her. And she’s still paying the bills.
The hospital declined to discuss Ms. Valle’s care, citing patient privacy. But 17 months before her 3-day ordeal, Tennova had outsourced its emergency departments to American Physician Partners, a medical staffing company owned by private equity investors. APP employs fewer doctors in its EDs as one of its cost-saving initiatives to increase earnings, according to a confidential company document obtained by KHN and NPR.
This staffing strategy has permeated hospitals, and particularly emergency departments, that seek to reduce their top expense: physician labor. While diagnosing and treating patients was once their domain, doctors are increasingly being replaced by nurse practitioners and physician assistants, collectively known as “midlevel practitioners,” who can perform many of the same duties and generate much of the same revenue for less than half of the pay.
“APP has numerous cost saving initiatives underway as part of the Company’s continual focus on cost optimization,” the document says, including a “shift of staffing” between doctors and midlevel practitioners.
In a statement to KHN, American Physician Partners said this strategy is a way to ensure all EDs remain fully staffed, calling it a “blended model” that allows doctors, nurse practitioners, and physician assistants “to provide care to their fullest potential.”
Critics of this strategy say the quest to save money results in treatment meted out by someone with far less training than a physician, leaving patients vulnerable to misdiagnoses, higher medical bills, and inadequate care. And these fears are bolstered by evidence that suggests dropping doctors from EDs may not be good for patients.
A working paper, published in October by the National Bureau of Economic Research, analyzed roughly 1.1 million visits to 44 EDs throughout the Veterans Health Administration, where nurse practitioners can treat patients without oversight from doctors.
Researchers found that treatment by a nurse practitioner resulted on average in a 7% increase in cost of care and an 11% increase in length of stay, extending patients’ time in the ED by minutes for minor visits and hours for longer ones. These gaps widened among patients with more severe diagnoses, the study said, but could be somewhat mitigated by nurse practitioners with more experience.
The study also found that ED patients treated by a nurse practitioner were 20% more likely to be readmitted to the hospital for a preventable reason within 30 days, although the overall risk of readmission remained very small.
Yiqun Chen, PhD, who is an assistant professor of economics at the University of Illinois at Chicago and coauthored the study, said these findings are not an indictment of nurse practitioners in the ED. Instead, she said, she hopes the study will guide how to best deploy nurse practitioners: in treatment of simpler patients or circumstances when no doctor is available.
“It’s not just a simple question of if we can substitute physicians with nurse practitioners or not,” Dr. Chen said. “It depends on how we use them. If we just use them as independent providers, especially ... for relatively complicated patients, it doesn’t seem to be a very good use.”
Dr. Chen’s research echoes smaller studies, like one from The Harvey L. Neiman Health Policy Institute that found nonphysician practitioners in EDs were associated with a 5.3% increase in imaging, which could unnecessarily increase bills for patients. Separately, a study at the Hattiesburg Clinic in Mississippi found that midlevel practitioners in primary care – not in the emergency department – increased the out-of-pocket costs to patients while also leading to worse performance on 9 of 10 quality-of-care metrics, including cancer screenings and vaccination rates.
But definitive evidence remains elusive that replacing ER doctors with nonphysicians has a negative impact on patients, said Cameron Gettel, MD, an assistant professor of emergency medicine at Yale University, New Haven, Conn. Private equity investment and the use of midlevel practitioners rose in lockstep in the ED, Dr. Gettel said, and in the absence of game-changing research, the pattern will likely continue.
“Worse patient outcomes haven’t really been shown across the board,” he said. “And I think until that is shown, then they will continue to play an increasing role.”
For private equity, dropping ED docs is a “simple equation”
Private equity companies pool money from wealthy investors to buy their way into various industries, often slashing spending and seeking to flip businesses in 3 to 7 years. While this business model is a proven moneymaker on Wall Street, it raises concerns in health care, where critics worry the pressure to turn big profits will influence life-or-death decisions that were once left solely to medical professionals.
Nearly $1 trillion in private equity funds have gone into almost 8,000 health care transactions over the past decade, according to industry tracker PitchBook, including buying into medical staffing companies that many hospitals hire to manage their emergency departments.
Two firms dominate the ED staffing industry: TeamHealth, bought by private equity firm Blackstone in 2016, and Envision Healthcare, bought by KKR in 2018. Trying to undercut these staffing giants is American Physician Partners, a rapidly expanding company that runs EDs in at least 17 states and is 50% owned by private equity firm BBH Capital Partners.
These staffing companies have been among the most aggressive in replacing doctors to cut costs, said Robert McNamara, MD, a founder of the American Academy of Emergency Medicine and chair of emergency medicine at Temple University, Philadelphia.
“It’s a relatively simple equation,” Dr. McNamara said. “Their No. 1 expense is the board-certified emergency physician. So they are going to want to keep that expense as low as possible.”
Not everyone sees the trend of private equity in ED staffing in a negative light. Jennifer Orozco, president of the American Academy of Physician Associates, which represents physician assistants, said even if the change – to use more nonphysician providers – is driven by the staffing firms’ desire to make more money, patients are still well served by a team approach that includes nurse practitioners and physician assistants.
“Though I see that shift, it’s not about profits at the end of the day,” Ms. Orozco said. “It’s about the patient.”
The “shift” is nearly invisible to patients because hospitals rarely promote branding from their ED staffing firms and there is little public documentation of private equity investments.
Arthur Smolensky, MD, a Tennessee emergency medicine specialist attempting to measure private equity’s intrusion into EDs, said his review of hospital job postings and employment contracts in 14 major metropolitan areas found that 43% of ED patients were seen in EDs staffed by companies with nonphysician owners, nearly all of whom are private equity investors.
Dr. Smolensky hopes to publish his full study, expanding to 55 metro areas, later this year. But this research will merely quantify what many doctors already know: The ED has changed. Demoralized by an increased focus on profit, and wary of a looming surplus of emergency medicine residents because there are fewer jobs to fill, many experienced doctors are leaving the ED on their own, he said.
“Most of us didn’t go into medicine to supervise an army of people that are not as well trained as we are,” Dr. Smolensky said. “We want to take care of patients.”
“I guess we’re the first guinea pigs for our ER”
Joshua Allen, a nurse practitioner at a small Kentucky hospital, snaked a rubber hose through a rack of pork ribs to practice inserting a chest tube to fix a collapsed lung.
It was 2020, and American Physician Partners was restructuring the ED where Mr. Allen worked, reducing shifts from two doctors to one. Once Mr. Allen had placed 10 tubes under a doctor’s supervision, he would be allowed to do it on his own.
“I guess we’re the first guinea pigs for our ER,” he said. “If we do have a major trauma and multiple victims come in, there’s only one doctor there. ... We need to be prepared.”
Mr. Allen is one of many midlevel practitioners finding work in emergency departments. Nurse practitioners and physician assistants are among the fastest-growing occupations in the nation, according to the U.S. Bureau of Labor Statistics.
Generally, they have master’s degrees and receive several years of specialized schooling but have significantly less training than doctors. Many are permitted to diagnose patients and prescribe medication with little or no supervision from a doctor, although limitations vary by state.
The Neiman Institute found that the share of ED visits in which a midlevel practitioner was the main clinician increased by more than 172% between 2005 and 2020. Another study, in the Journal of Emergency Medicine, reported that if trends continue there may be equal numbers of midlevel practitioners and doctors in EDs by 2030.
There is little mystery as to why. Federal data shows emergency medicine doctors are paid about $310,000 a year on average, while nurse practitioners and physician assistants earn less than $120,000. Generally, hospitals can bill for care by a midlevel practitioner at 85% the rate of a doctor while paying them less than half as much.
Private equity can make millions in the gap.
For example, Envision once encouraged EDs to employ “the least expensive resource” and treat up to 35% of patients with midlevel practitioners, according to a 2017 PowerPoint presentation. The presentation drew scorn on social media and disappeared from Envision’s website.
Envision declined a request for a phone interview. In a written statement to KHN, spokesperson Aliese Polk said the company does not direct its physician leaders on how to care for patients and called the presentation a “concept guide” that does not represent current views.
American Physician Partners touted roughly the same staffing strategy in 2021 in response to the No Surprises Act, which threatened the company’s profits by outlawing surprise medical bills. In its confidential pitch to lenders, the company estimated it could cut almost $6 million by shifting more staffing from physicians to midlevel practitioners.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
She didn’t know much about miscarriage, but this seemed like one.
In the emergency department, she was examined then sent home, she said. She went back when her cramping became excruciating. Then home again. It ultimately took three trips to the ED on 3 consecutive days, generating three separate bills, before she saw a doctor who looked at her blood work and confirmed her fears.
“At the time I wasn’t thinking, ‘Oh, I need to see a doctor,’ ” Ms. Valle recalled. “But when you think about it, it’s like, ‘Well, dang – why didn’t I see a doctor?’ ” It’s unclear whether the repeat visits were due to delays in seeing a physician, but the experience worried her. And she’s still paying the bills.
The hospital declined to discuss Ms. Valle’s care, citing patient privacy. But 17 months before her 3-day ordeal, Tennova had outsourced its emergency departments to American Physician Partners, a medical staffing company owned by private equity investors. APP employs fewer doctors in its EDs as one of its cost-saving initiatives to increase earnings, according to a confidential company document obtained by KHN and NPR.
This staffing strategy has permeated hospitals, and particularly emergency departments, that seek to reduce their top expense: physician labor. While diagnosing and treating patients was once their domain, doctors are increasingly being replaced by nurse practitioners and physician assistants, collectively known as “midlevel practitioners,” who can perform many of the same duties and generate much of the same revenue for less than half of the pay.
“APP has numerous cost saving initiatives underway as part of the Company’s continual focus on cost optimization,” the document says, including a “shift of staffing” between doctors and midlevel practitioners.
In a statement to KHN, American Physician Partners said this strategy is a way to ensure all EDs remain fully staffed, calling it a “blended model” that allows doctors, nurse practitioners, and physician assistants “to provide care to their fullest potential.”
Critics of this strategy say the quest to save money results in treatment meted out by someone with far less training than a physician, leaving patients vulnerable to misdiagnoses, higher medical bills, and inadequate care. And these fears are bolstered by evidence that suggests dropping doctors from EDs may not be good for patients.
A working paper, published in October by the National Bureau of Economic Research, analyzed roughly 1.1 million visits to 44 EDs throughout the Veterans Health Administration, where nurse practitioners can treat patients without oversight from doctors.
Researchers found that treatment by a nurse practitioner resulted on average in a 7% increase in cost of care and an 11% increase in length of stay, extending patients’ time in the ED by minutes for minor visits and hours for longer ones. These gaps widened among patients with more severe diagnoses, the study said, but could be somewhat mitigated by nurse practitioners with more experience.
The study also found that ED patients treated by a nurse practitioner were 20% more likely to be readmitted to the hospital for a preventable reason within 30 days, although the overall risk of readmission remained very small.
Yiqun Chen, PhD, who is an assistant professor of economics at the University of Illinois at Chicago and coauthored the study, said these findings are not an indictment of nurse practitioners in the ED. Instead, she said, she hopes the study will guide how to best deploy nurse practitioners: in treatment of simpler patients or circumstances when no doctor is available.
“It’s not just a simple question of if we can substitute physicians with nurse practitioners or not,” Dr. Chen said. “It depends on how we use them. If we just use them as independent providers, especially ... for relatively complicated patients, it doesn’t seem to be a very good use.”
Dr. Chen’s research echoes smaller studies, like one from The Harvey L. Neiman Health Policy Institute that found nonphysician practitioners in EDs were associated with a 5.3% increase in imaging, which could unnecessarily increase bills for patients. Separately, a study at the Hattiesburg Clinic in Mississippi found that midlevel practitioners in primary care – not in the emergency department – increased the out-of-pocket costs to patients while also leading to worse performance on 9 of 10 quality-of-care metrics, including cancer screenings and vaccination rates.
But definitive evidence remains elusive that replacing ER doctors with nonphysicians has a negative impact on patients, said Cameron Gettel, MD, an assistant professor of emergency medicine at Yale University, New Haven, Conn. Private equity investment and the use of midlevel practitioners rose in lockstep in the ED, Dr. Gettel said, and in the absence of game-changing research, the pattern will likely continue.
“Worse patient outcomes haven’t really been shown across the board,” he said. “And I think until that is shown, then they will continue to play an increasing role.”
For private equity, dropping ED docs is a “simple equation”
Private equity companies pool money from wealthy investors to buy their way into various industries, often slashing spending and seeking to flip businesses in 3 to 7 years. While this business model is a proven moneymaker on Wall Street, it raises concerns in health care, where critics worry the pressure to turn big profits will influence life-or-death decisions that were once left solely to medical professionals.
Nearly $1 trillion in private equity funds have gone into almost 8,000 health care transactions over the past decade, according to industry tracker PitchBook, including buying into medical staffing companies that many hospitals hire to manage their emergency departments.
Two firms dominate the ED staffing industry: TeamHealth, bought by private equity firm Blackstone in 2016, and Envision Healthcare, bought by KKR in 2018. Trying to undercut these staffing giants is American Physician Partners, a rapidly expanding company that runs EDs in at least 17 states and is 50% owned by private equity firm BBH Capital Partners.
These staffing companies have been among the most aggressive in replacing doctors to cut costs, said Robert McNamara, MD, a founder of the American Academy of Emergency Medicine and chair of emergency medicine at Temple University, Philadelphia.
“It’s a relatively simple equation,” Dr. McNamara said. “Their No. 1 expense is the board-certified emergency physician. So they are going to want to keep that expense as low as possible.”
Not everyone sees the trend of private equity in ED staffing in a negative light. Jennifer Orozco, president of the American Academy of Physician Associates, which represents physician assistants, said even if the change – to use more nonphysician providers – is driven by the staffing firms’ desire to make more money, patients are still well served by a team approach that includes nurse practitioners and physician assistants.
“Though I see that shift, it’s not about profits at the end of the day,” Ms. Orozco said. “It’s about the patient.”
The “shift” is nearly invisible to patients because hospitals rarely promote branding from their ED staffing firms and there is little public documentation of private equity investments.
Arthur Smolensky, MD, a Tennessee emergency medicine specialist attempting to measure private equity’s intrusion into EDs, said his review of hospital job postings and employment contracts in 14 major metropolitan areas found that 43% of ED patients were seen in EDs staffed by companies with nonphysician owners, nearly all of whom are private equity investors.
Dr. Smolensky hopes to publish his full study, expanding to 55 metro areas, later this year. But this research will merely quantify what many doctors already know: The ED has changed. Demoralized by an increased focus on profit, and wary of a looming surplus of emergency medicine residents because there are fewer jobs to fill, many experienced doctors are leaving the ED on their own, he said.
“Most of us didn’t go into medicine to supervise an army of people that are not as well trained as we are,” Dr. Smolensky said. “We want to take care of patients.”
“I guess we’re the first guinea pigs for our ER”
Joshua Allen, a nurse practitioner at a small Kentucky hospital, snaked a rubber hose through a rack of pork ribs to practice inserting a chest tube to fix a collapsed lung.
It was 2020, and American Physician Partners was restructuring the ED where Mr. Allen worked, reducing shifts from two doctors to one. Once Mr. Allen had placed 10 tubes under a doctor’s supervision, he would be allowed to do it on his own.
“I guess we’re the first guinea pigs for our ER,” he said. “If we do have a major trauma and multiple victims come in, there’s only one doctor there. ... We need to be prepared.”
Mr. Allen is one of many midlevel practitioners finding work in emergency departments. Nurse practitioners and physician assistants are among the fastest-growing occupations in the nation, according to the U.S. Bureau of Labor Statistics.
Generally, they have master’s degrees and receive several years of specialized schooling but have significantly less training than doctors. Many are permitted to diagnose patients and prescribe medication with little or no supervision from a doctor, although limitations vary by state.
The Neiman Institute found that the share of ED visits in which a midlevel practitioner was the main clinician increased by more than 172% between 2005 and 2020. Another study, in the Journal of Emergency Medicine, reported that if trends continue there may be equal numbers of midlevel practitioners and doctors in EDs by 2030.
There is little mystery as to why. Federal data shows emergency medicine doctors are paid about $310,000 a year on average, while nurse practitioners and physician assistants earn less than $120,000. Generally, hospitals can bill for care by a midlevel practitioner at 85% the rate of a doctor while paying them less than half as much.
Private equity can make millions in the gap.
For example, Envision once encouraged EDs to employ “the least expensive resource” and treat up to 35% of patients with midlevel practitioners, according to a 2017 PowerPoint presentation. The presentation drew scorn on social media and disappeared from Envision’s website.
Envision declined a request for a phone interview. In a written statement to KHN, spokesperson Aliese Polk said the company does not direct its physician leaders on how to care for patients and called the presentation a “concept guide” that does not represent current views.
American Physician Partners touted roughly the same staffing strategy in 2021 in response to the No Surprises Act, which threatened the company’s profits by outlawing surprise medical bills. In its confidential pitch to lenders, the company estimated it could cut almost $6 million by shifting more staffing from physicians to midlevel practitioners.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Scientists create ‘vagina on a chip’: What to know
For years, women’s health advocates have argued that far more research is needed on women’s bodies and health. The world’s first-ever “vagina on a chip,” recently developed at Harvard’s Wyss Institute for Biologically Inspired Engineering in Boston, could go a long way to making that happen.
“Women’s health has not received the attention it deserves,” says Don Ingber, MD, PhD, who led the team that created the vagina chip. The advance quickly drew media attention after it was reported in the journal Microbiome. But researchers hope for more than headlines. They see the chip as a way to facilitate vaginal health research and open the door to vital new treatments.
By now, you may have heard of “organs on chips”: tiny devices about the size of a flash drive that are designed to mimic the biological activity of human organs. These glass chips contain living human cells within grooves that allow the passage of fluid, to either maintain or disrupt the cells’ function. So far, Dr. Ingber and his team at the Wyss Institute have developed more than 15 organ chip models, including chips that mimic the lung, intestine, kidney, and bone marrow.
The idea to develop a vagina chip grew out of research, funded by the Gates Foundation, on a childhood disease called environmental enteric dysfunction, an intestinal disease most commonly found in low-resource nations that is the second leading cause of death in children under 5. That’s when Dr. Ingber discovered just how much the child’s microbiome influences this disease.
Stemming from that work, the Gates Foundation turned its attention to newborn health – in particular, the impact of bacterial vaginosis, an imbalance in the vagina’s bacterial makeup. Bacterial vaginosis occurs in one out of four women worldwide and has been linked to premature birth as well as HIV, HPV persistence, and cervical cancer.
The goal was to test “live biotherapeutic products,” or living microbes like probiotics, that might restore the vagina’s microbiome to health.
No other preclinical model exists to perform tests like that, says Dr. Ingber.
“The vagina chip is a way to help make some advances,” he says.
The Gates Foundation recognized that women’s reproductive health is a major issue, not only in low-income nations, but everywhere around the world. As the project evolved, Dr. Ingber began to hear from female colleagues about how neglected women’s reproductive health is in medical science.
“It is something I became sensitive to and realized this is just the starting point,” Dr. Ingber says.
Take bacterial vaginosis, for example. Since 1982, treatment has revolved around the same two antibiotics. That’s partly because there is no animal model to study. No other species has the same vaginal bacterial community as humans do.
That makes developing any new therapy “incredibly challenging,” explains Caroline Mitchell, MD, MPH, an ob.gyn. at Massachusetts General Hospital, Boston, and a member of the consortium.
It turns out, replicating the vagina in a lab dish is, to use the technical term, very hard.
“That’s where a vagina chip offers an opportunity,” Dr. Mitchell says. “It’s not super-high throughput, but it’s way more high throughput than a [human] clinical trial.”
As such, the vagina chip could help scientists find new treatments much faster.
Like Dr. Ingber, Dr. Mitchell also sees the chip as a way to bring more attention to the largely unmet needs in female reproductive medicine.
“Women’s reproductive health has been under-resourced, under-prioritized, and largely disregarded for decades,” she says. And the time may be ripe for change: Dr. Mitchell says she was encouraged by the National Institutes of Health’s Advancing NIH Research on the Health of Women conference, held in 2021 in response to a congressional request to address women’s health research efforts.
Beyond bacterial vaginosis, Dr. Mitchell imagines the chip could help scientists find new treatments for vaginal yeast infection (candidiasis), chlamydia, and endometriosis. As with bacterial vaginosis, medicines for vaginal yeast infections have not advanced in decades, Dr. Mitchell says. Efforts to develop a vaccine for chlamydia – which can cause permanent damage to a woman’s reproductive system – have dragged on for many years. And endometriosis, an often painful condition in which the tissue that makes up the uterine lining grows outside the uterus, remains under-researched despite affecting 10% of childbearing-age women.
While some mouse models are used in chlamydia research, it’s hard to say if they’ll translate to humans, given the vaginal and cervical bacterial differences.
“Our understanding of the basic physiology of the environment of the vagina and cervix is another area where we’re woefully ignorant,” Dr. Mitchell says.
To that end, Dr. Ingber’s team is developing more complex chips mimicking the vagina and the cervix. One of his team members wants to use the chips to study infertility. The researchers have already used the chips to see how bacterial vaginosis and mucous changes impact the way sperm migrates up the reproductive tract.
The lab is now linking vagina and cervix chips together to study viral infections of the cervix, like HPV, and all types of bacterial diseases of the vaginal tract. By applying cervical mucus to the vagina chip, they hope to learn more about how female reproductive tissues respond to infection and inflammation.
“I always say that organ chips are like synthetic biology at the cell tissue and organ level,” says Dr. Ingber. “You start simple and see if you [can] mimic a clinical situation.”
As they make the chips more complex – perhaps by adding blood vessel cells and female hormones – Dr. Ingber foresees being able to study the response to hormonal changes during the menstrual cycle.
“We can begin to explore the effects of cycling over time as well as other types of hormonal effects,” he says.
Dr. Ingber also envisions linking the vagina chip to other organ chips – he’s already succeeded in linking eight different organ types together. But for now, the team hopes the vagina chip will enhance our understanding of basic female reproductive biology and speed up the process of developing new treatments for women’s health.
A version of this article first appeared on WebMD.com.
For years, women’s health advocates have argued that far more research is needed on women’s bodies and health. The world’s first-ever “vagina on a chip,” recently developed at Harvard’s Wyss Institute for Biologically Inspired Engineering in Boston, could go a long way to making that happen.
“Women’s health has not received the attention it deserves,” says Don Ingber, MD, PhD, who led the team that created the vagina chip. The advance quickly drew media attention after it was reported in the journal Microbiome. But researchers hope for more than headlines. They see the chip as a way to facilitate vaginal health research and open the door to vital new treatments.
By now, you may have heard of “organs on chips”: tiny devices about the size of a flash drive that are designed to mimic the biological activity of human organs. These glass chips contain living human cells within grooves that allow the passage of fluid, to either maintain or disrupt the cells’ function. So far, Dr. Ingber and his team at the Wyss Institute have developed more than 15 organ chip models, including chips that mimic the lung, intestine, kidney, and bone marrow.
The idea to develop a vagina chip grew out of research, funded by the Gates Foundation, on a childhood disease called environmental enteric dysfunction, an intestinal disease most commonly found in low-resource nations that is the second leading cause of death in children under 5. That’s when Dr. Ingber discovered just how much the child’s microbiome influences this disease.
Stemming from that work, the Gates Foundation turned its attention to newborn health – in particular, the impact of bacterial vaginosis, an imbalance in the vagina’s bacterial makeup. Bacterial vaginosis occurs in one out of four women worldwide and has been linked to premature birth as well as HIV, HPV persistence, and cervical cancer.
The goal was to test “live biotherapeutic products,” or living microbes like probiotics, that might restore the vagina’s microbiome to health.
No other preclinical model exists to perform tests like that, says Dr. Ingber.
“The vagina chip is a way to help make some advances,” he says.
The Gates Foundation recognized that women’s reproductive health is a major issue, not only in low-income nations, but everywhere around the world. As the project evolved, Dr. Ingber began to hear from female colleagues about how neglected women’s reproductive health is in medical science.
“It is something I became sensitive to and realized this is just the starting point,” Dr. Ingber says.
Take bacterial vaginosis, for example. Since 1982, treatment has revolved around the same two antibiotics. That’s partly because there is no animal model to study. No other species has the same vaginal bacterial community as humans do.
That makes developing any new therapy “incredibly challenging,” explains Caroline Mitchell, MD, MPH, an ob.gyn. at Massachusetts General Hospital, Boston, and a member of the consortium.
It turns out, replicating the vagina in a lab dish is, to use the technical term, very hard.
“That’s where a vagina chip offers an opportunity,” Dr. Mitchell says. “It’s not super-high throughput, but it’s way more high throughput than a [human] clinical trial.”
As such, the vagina chip could help scientists find new treatments much faster.
Like Dr. Ingber, Dr. Mitchell also sees the chip as a way to bring more attention to the largely unmet needs in female reproductive medicine.
“Women’s reproductive health has been under-resourced, under-prioritized, and largely disregarded for decades,” she says. And the time may be ripe for change: Dr. Mitchell says she was encouraged by the National Institutes of Health’s Advancing NIH Research on the Health of Women conference, held in 2021 in response to a congressional request to address women’s health research efforts.
Beyond bacterial vaginosis, Dr. Mitchell imagines the chip could help scientists find new treatments for vaginal yeast infection (candidiasis), chlamydia, and endometriosis. As with bacterial vaginosis, medicines for vaginal yeast infections have not advanced in decades, Dr. Mitchell says. Efforts to develop a vaccine for chlamydia – which can cause permanent damage to a woman’s reproductive system – have dragged on for many years. And endometriosis, an often painful condition in which the tissue that makes up the uterine lining grows outside the uterus, remains under-researched despite affecting 10% of childbearing-age women.
While some mouse models are used in chlamydia research, it’s hard to say if they’ll translate to humans, given the vaginal and cervical bacterial differences.
“Our understanding of the basic physiology of the environment of the vagina and cervix is another area where we’re woefully ignorant,” Dr. Mitchell says.
To that end, Dr. Ingber’s team is developing more complex chips mimicking the vagina and the cervix. One of his team members wants to use the chips to study infertility. The researchers have already used the chips to see how bacterial vaginosis and mucous changes impact the way sperm migrates up the reproductive tract.
The lab is now linking vagina and cervix chips together to study viral infections of the cervix, like HPV, and all types of bacterial diseases of the vaginal tract. By applying cervical mucus to the vagina chip, they hope to learn more about how female reproductive tissues respond to infection and inflammation.
“I always say that organ chips are like synthetic biology at the cell tissue and organ level,” says Dr. Ingber. “You start simple and see if you [can] mimic a clinical situation.”
As they make the chips more complex – perhaps by adding blood vessel cells and female hormones – Dr. Ingber foresees being able to study the response to hormonal changes during the menstrual cycle.
“We can begin to explore the effects of cycling over time as well as other types of hormonal effects,” he says.
Dr. Ingber also envisions linking the vagina chip to other organ chips – he’s already succeeded in linking eight different organ types together. But for now, the team hopes the vagina chip will enhance our understanding of basic female reproductive biology and speed up the process of developing new treatments for women’s health.
A version of this article first appeared on WebMD.com.
For years, women’s health advocates have argued that far more research is needed on women’s bodies and health. The world’s first-ever “vagina on a chip,” recently developed at Harvard’s Wyss Institute for Biologically Inspired Engineering in Boston, could go a long way to making that happen.
“Women’s health has not received the attention it deserves,” says Don Ingber, MD, PhD, who led the team that created the vagina chip. The advance quickly drew media attention after it was reported in the journal Microbiome. But researchers hope for more than headlines. They see the chip as a way to facilitate vaginal health research and open the door to vital new treatments.
By now, you may have heard of “organs on chips”: tiny devices about the size of a flash drive that are designed to mimic the biological activity of human organs. These glass chips contain living human cells within grooves that allow the passage of fluid, to either maintain or disrupt the cells’ function. So far, Dr. Ingber and his team at the Wyss Institute have developed more than 15 organ chip models, including chips that mimic the lung, intestine, kidney, and bone marrow.
The idea to develop a vagina chip grew out of research, funded by the Gates Foundation, on a childhood disease called environmental enteric dysfunction, an intestinal disease most commonly found in low-resource nations that is the second leading cause of death in children under 5. That’s when Dr. Ingber discovered just how much the child’s microbiome influences this disease.
Stemming from that work, the Gates Foundation turned its attention to newborn health – in particular, the impact of bacterial vaginosis, an imbalance in the vagina’s bacterial makeup. Bacterial vaginosis occurs in one out of four women worldwide and has been linked to premature birth as well as HIV, HPV persistence, and cervical cancer.
The goal was to test “live biotherapeutic products,” or living microbes like probiotics, that might restore the vagina’s microbiome to health.
No other preclinical model exists to perform tests like that, says Dr. Ingber.
“The vagina chip is a way to help make some advances,” he says.
The Gates Foundation recognized that women’s reproductive health is a major issue, not only in low-income nations, but everywhere around the world. As the project evolved, Dr. Ingber began to hear from female colleagues about how neglected women’s reproductive health is in medical science.
“It is something I became sensitive to and realized this is just the starting point,” Dr. Ingber says.
Take bacterial vaginosis, for example. Since 1982, treatment has revolved around the same two antibiotics. That’s partly because there is no animal model to study. No other species has the same vaginal bacterial community as humans do.
That makes developing any new therapy “incredibly challenging,” explains Caroline Mitchell, MD, MPH, an ob.gyn. at Massachusetts General Hospital, Boston, and a member of the consortium.
It turns out, replicating the vagina in a lab dish is, to use the technical term, very hard.
“That’s where a vagina chip offers an opportunity,” Dr. Mitchell says. “It’s not super-high throughput, but it’s way more high throughput than a [human] clinical trial.”
As such, the vagina chip could help scientists find new treatments much faster.
Like Dr. Ingber, Dr. Mitchell also sees the chip as a way to bring more attention to the largely unmet needs in female reproductive medicine.
“Women’s reproductive health has been under-resourced, under-prioritized, and largely disregarded for decades,” she says. And the time may be ripe for change: Dr. Mitchell says she was encouraged by the National Institutes of Health’s Advancing NIH Research on the Health of Women conference, held in 2021 in response to a congressional request to address women’s health research efforts.
Beyond bacterial vaginosis, Dr. Mitchell imagines the chip could help scientists find new treatments for vaginal yeast infection (candidiasis), chlamydia, and endometriosis. As with bacterial vaginosis, medicines for vaginal yeast infections have not advanced in decades, Dr. Mitchell says. Efforts to develop a vaccine for chlamydia – which can cause permanent damage to a woman’s reproductive system – have dragged on for many years. And endometriosis, an often painful condition in which the tissue that makes up the uterine lining grows outside the uterus, remains under-researched despite affecting 10% of childbearing-age women.
While some mouse models are used in chlamydia research, it’s hard to say if they’ll translate to humans, given the vaginal and cervical bacterial differences.
“Our understanding of the basic physiology of the environment of the vagina and cervix is another area where we’re woefully ignorant,” Dr. Mitchell says.
To that end, Dr. Ingber’s team is developing more complex chips mimicking the vagina and the cervix. One of his team members wants to use the chips to study infertility. The researchers have already used the chips to see how bacterial vaginosis and mucous changes impact the way sperm migrates up the reproductive tract.
The lab is now linking vagina and cervix chips together to study viral infections of the cervix, like HPV, and all types of bacterial diseases of the vaginal tract. By applying cervical mucus to the vagina chip, they hope to learn more about how female reproductive tissues respond to infection and inflammation.
“I always say that organ chips are like synthetic biology at the cell tissue and organ level,” says Dr. Ingber. “You start simple and see if you [can] mimic a clinical situation.”
As they make the chips more complex – perhaps by adding blood vessel cells and female hormones – Dr. Ingber foresees being able to study the response to hormonal changes during the menstrual cycle.
“We can begin to explore the effects of cycling over time as well as other types of hormonal effects,” he says.
Dr. Ingber also envisions linking the vagina chip to other organ chips – he’s already succeeded in linking eight different organ types together. But for now, the team hopes the vagina chip will enhance our understanding of basic female reproductive biology and speed up the process of developing new treatments for women’s health.
A version of this article first appeared on WebMD.com.
FROM MICROBIOME
Three wild technologies about to change health care
When I was a child, I watched syndicated episodes of the original “Star Trek.” I was dazzled by the space travel, sure, but also the medical technology.
A handheld “tricorder” detected diseases, while an intramuscular injector (“hypospray”) could treat them. Sickbay “biobeds” came with real-time health monitors that looked futuristic at the time but seem primitive today.
Such visions inspired a lot of us kids to pursue science. Little did we know the real-life advances many of us would see in our lifetimes.
Artificial intelligence helping to spot disease, robots performing surgery, even video calls between doctor and patient – all these once sounded fantastical but now happen in clinical care.
Now, in the 23rd year of the 21st century, you might not believe wht we’ll be capable of next. Three especially wild examples are moving closer to clinical reality.
Human hibernation
Captain America, Han Solo, and “Star Trek” villain Khan – all were preserved at low temperatures and then revived, waking up alive and well months, decades, or centuries later. These are fictional examples, to be sure, but the science they’re rooted in is real.
(In one extreme case, a climber survived after almost 9 hours of efforts to revive him.)
Useful for a space traveler? Maybe not. But it’s potentially huge for someone with life-threatening injuries from a car accident or a gunshot wound.
That’s the thinking behind a breakthrough procedure that came after decades of research on pigs and dogs, now in a clinical trial. The idea: A person with massive blood loss whose heart has stopped is injected with an ice-cold fluid, cooling them from the inside, down to about 50° F.
Doctors already induce more modest hypothermia to protect the brain and other organs after cardiac arrest and during surgery on the aortic arch (the main artery carrying blood from the heart).
But this experimental procedure – called emergency preservation and resuscitation (EPR) – goes far beyond that, dramatically “decreasing the body’s need for oxygen and blood flow,” says Samuel Tisherman, MD, a trauma surgeon at the University of Maryland Medical Center and the trial’s lead researcher. This puts the patient in a state of suspended animation that “could buy time for surgeons to stop the bleeding and save more of these patients.”
The technique has been done on at least six patients, though none were reported to survive. The trial is expected to include 20 people by the time it wraps up in December, according to the listing on the U.S. clinical trials database. Though given the strict requirements for candidates (emergency trauma victims who are not likely to survive), one can’t exactly rely on a set schedule.
Still, the technology is promising. Someday we may even use it to keep patients in suspended animation for months or years, experts predict, helping astronauts through decades-long spaceflights, or stalling death in sick patients awaiting a cure.
Artificial womb
Another sci-fi classic: growing human babies outside the womb. Think the fetus fields from “The Matrix,” or the frozen embryos in “Alien: Covenant.”
In 1923, British biologist J.B.S. Haldane coined a term for that – ectogenesis. He predicted that 70% of pregnancies would take place, from fertilization to birth, in artificial wombs by 2074. That many seems unlikely, but the timeline is on track.
Developing an embryo outside the womb is already routine in in vitro fertilization. And technology enables preterm babies to survive through much of the second half of gestation. Normal human pregnancy is 40 weeks, and the youngest preterm baby ever to survive was 21 weeks and 1 day old, just a few days younger than a smattering of others who lived.
The biggest obstacle for babies younger than that is lung viability. Mechanical ventilation can damage the lungs and lead to a chronic (sometimes fatal) lung disease known as bronchopulmonary dysplasia. Avoiding this would mean figuring out a way to maintain fetal circulation – the intricate system that delivers oxygenated blood from the placenta to the fetus via the umbilical cord. Researchers at Children’s Hospital of Philadelphia have done this using a fetal lamb.
The key to their invention is a substitute placenta: an oxygenator connected to the lamb’s umbilical cord. Tubes inserted through the umbilical vein and arteries carry oxygenated blood from the “placenta” to the fetus, and deoxygenated blood back out. The lamb resides in an artificial, fluid-filled amniotic sac until its lungs and other organs are developed.
Fertility treatment could benefit, too. “An artificial womb may substitute in situations in which a gestational carrier – surrogate – is indicated,” says Paula Amato, MD, a professor of obstetrics and gynecology at Oregon Health and Science University, Portland. (Dr. Amato is not involved in the CHOP research.) For example: when the mother is missing a uterus or can’t carry a pregnancy safely.
No date is set for clinical trials yet. But according to the research, the main difference between human and lamb may come down to size. A lamb’s umbilical vessels are larger, so feeding in a tube is easier. With today’s advances in miniaturizing surgical methods, that seems like a challenge scientists can overcome.
Messenger RNA therapeutics
Back to “Star Trek.” The hypospray injector’s contents could cure just about any disease, even one newly discovered on a strange planet. That’s not unlike messenger RNA (mRNA) technology, a breakthrough that enabled scientists to quickly develop some of the first COVID-19 vaccines.
But vaccines are just the beginning of what this technology can do.
A whole field of immunotherapy is emerging that uses mRNA to deliver instructions to produce chimeric antigen receptor–modified immune cells (CAR-modified immune cells). These cells are engineered to target diseased cells and tissues, like cancer cells and harmful fibroblasts (scar tissue) that promote fibrosis in, for example, the heart and lungs.
The field is bursting with rodent research, and clinical trials have started for treating some advanced-stage malignancies.
Actual clinical use may be years away, but if all goes well, these medicines could help treat or even cure the core medical problems facing humanity. We’re talking cancer, heart disease, neurodegenerative disease – transforming one therapy into another by simply changing the mRNA’s “nucleotide sequence,” the blueprint containing instructions telling it what to do, and what disease to attack.
As this technology matures, we may start to feel as if we’re really on “Star Trek,” where Dr. Leonard “Bones” McCoy pulls out the same device to treat just about every disease or injury.
A version of this article first appeared on WebMD.com.
When I was a child, I watched syndicated episodes of the original “Star Trek.” I was dazzled by the space travel, sure, but also the medical technology.
A handheld “tricorder” detected diseases, while an intramuscular injector (“hypospray”) could treat them. Sickbay “biobeds” came with real-time health monitors that looked futuristic at the time but seem primitive today.
Such visions inspired a lot of us kids to pursue science. Little did we know the real-life advances many of us would see in our lifetimes.
Artificial intelligence helping to spot disease, robots performing surgery, even video calls between doctor and patient – all these once sounded fantastical but now happen in clinical care.
Now, in the 23rd year of the 21st century, you might not believe wht we’ll be capable of next. Three especially wild examples are moving closer to clinical reality.
Human hibernation
Captain America, Han Solo, and “Star Trek” villain Khan – all were preserved at low temperatures and then revived, waking up alive and well months, decades, or centuries later. These are fictional examples, to be sure, but the science they’re rooted in is real.
(In one extreme case, a climber survived after almost 9 hours of efforts to revive him.)
Useful for a space traveler? Maybe not. But it’s potentially huge for someone with life-threatening injuries from a car accident or a gunshot wound.
That’s the thinking behind a breakthrough procedure that came after decades of research on pigs and dogs, now in a clinical trial. The idea: A person with massive blood loss whose heart has stopped is injected with an ice-cold fluid, cooling them from the inside, down to about 50° F.
Doctors already induce more modest hypothermia to protect the brain and other organs after cardiac arrest and during surgery on the aortic arch (the main artery carrying blood from the heart).
But this experimental procedure – called emergency preservation and resuscitation (EPR) – goes far beyond that, dramatically “decreasing the body’s need for oxygen and blood flow,” says Samuel Tisherman, MD, a trauma surgeon at the University of Maryland Medical Center and the trial’s lead researcher. This puts the patient in a state of suspended animation that “could buy time for surgeons to stop the bleeding and save more of these patients.”
The technique has been done on at least six patients, though none were reported to survive. The trial is expected to include 20 people by the time it wraps up in December, according to the listing on the U.S. clinical trials database. Though given the strict requirements for candidates (emergency trauma victims who are not likely to survive), one can’t exactly rely on a set schedule.
Still, the technology is promising. Someday we may even use it to keep patients in suspended animation for months or years, experts predict, helping astronauts through decades-long spaceflights, or stalling death in sick patients awaiting a cure.
Artificial womb
Another sci-fi classic: growing human babies outside the womb. Think the fetus fields from “The Matrix,” or the frozen embryos in “Alien: Covenant.”
In 1923, British biologist J.B.S. Haldane coined a term for that – ectogenesis. He predicted that 70% of pregnancies would take place, from fertilization to birth, in artificial wombs by 2074. That many seems unlikely, but the timeline is on track.
Developing an embryo outside the womb is already routine in in vitro fertilization. And technology enables preterm babies to survive through much of the second half of gestation. Normal human pregnancy is 40 weeks, and the youngest preterm baby ever to survive was 21 weeks and 1 day old, just a few days younger than a smattering of others who lived.
The biggest obstacle for babies younger than that is lung viability. Mechanical ventilation can damage the lungs and lead to a chronic (sometimes fatal) lung disease known as bronchopulmonary dysplasia. Avoiding this would mean figuring out a way to maintain fetal circulation – the intricate system that delivers oxygenated blood from the placenta to the fetus via the umbilical cord. Researchers at Children’s Hospital of Philadelphia have done this using a fetal lamb.
The key to their invention is a substitute placenta: an oxygenator connected to the lamb’s umbilical cord. Tubes inserted through the umbilical vein and arteries carry oxygenated blood from the “placenta” to the fetus, and deoxygenated blood back out. The lamb resides in an artificial, fluid-filled amniotic sac until its lungs and other organs are developed.
Fertility treatment could benefit, too. “An artificial womb may substitute in situations in which a gestational carrier – surrogate – is indicated,” says Paula Amato, MD, a professor of obstetrics and gynecology at Oregon Health and Science University, Portland. (Dr. Amato is not involved in the CHOP research.) For example: when the mother is missing a uterus or can’t carry a pregnancy safely.
No date is set for clinical trials yet. But according to the research, the main difference between human and lamb may come down to size. A lamb’s umbilical vessels are larger, so feeding in a tube is easier. With today’s advances in miniaturizing surgical methods, that seems like a challenge scientists can overcome.
Messenger RNA therapeutics
Back to “Star Trek.” The hypospray injector’s contents could cure just about any disease, even one newly discovered on a strange planet. That’s not unlike messenger RNA (mRNA) technology, a breakthrough that enabled scientists to quickly develop some of the first COVID-19 vaccines.
But vaccines are just the beginning of what this technology can do.
A whole field of immunotherapy is emerging that uses mRNA to deliver instructions to produce chimeric antigen receptor–modified immune cells (CAR-modified immune cells). These cells are engineered to target diseased cells and tissues, like cancer cells and harmful fibroblasts (scar tissue) that promote fibrosis in, for example, the heart and lungs.
The field is bursting with rodent research, and clinical trials have started for treating some advanced-stage malignancies.
Actual clinical use may be years away, but if all goes well, these medicines could help treat or even cure the core medical problems facing humanity. We’re talking cancer, heart disease, neurodegenerative disease – transforming one therapy into another by simply changing the mRNA’s “nucleotide sequence,” the blueprint containing instructions telling it what to do, and what disease to attack.
As this technology matures, we may start to feel as if we’re really on “Star Trek,” where Dr. Leonard “Bones” McCoy pulls out the same device to treat just about every disease or injury.
A version of this article first appeared on WebMD.com.
When I was a child, I watched syndicated episodes of the original “Star Trek.” I was dazzled by the space travel, sure, but also the medical technology.
A handheld “tricorder” detected diseases, while an intramuscular injector (“hypospray”) could treat them. Sickbay “biobeds” came with real-time health monitors that looked futuristic at the time but seem primitive today.
Such visions inspired a lot of us kids to pursue science. Little did we know the real-life advances many of us would see in our lifetimes.
Artificial intelligence helping to spot disease, robots performing surgery, even video calls between doctor and patient – all these once sounded fantastical but now happen in clinical care.
Now, in the 23rd year of the 21st century, you might not believe wht we’ll be capable of next. Three especially wild examples are moving closer to clinical reality.
Human hibernation
Captain America, Han Solo, and “Star Trek” villain Khan – all were preserved at low temperatures and then revived, waking up alive and well months, decades, or centuries later. These are fictional examples, to be sure, but the science they’re rooted in is real.
(In one extreme case, a climber survived after almost 9 hours of efforts to revive him.)
Useful for a space traveler? Maybe not. But it’s potentially huge for someone with life-threatening injuries from a car accident or a gunshot wound.
That’s the thinking behind a breakthrough procedure that came after decades of research on pigs and dogs, now in a clinical trial. The idea: A person with massive blood loss whose heart has stopped is injected with an ice-cold fluid, cooling them from the inside, down to about 50° F.
Doctors already induce more modest hypothermia to protect the brain and other organs after cardiac arrest and during surgery on the aortic arch (the main artery carrying blood from the heart).
But this experimental procedure – called emergency preservation and resuscitation (EPR) – goes far beyond that, dramatically “decreasing the body’s need for oxygen and blood flow,” says Samuel Tisherman, MD, a trauma surgeon at the University of Maryland Medical Center and the trial’s lead researcher. This puts the patient in a state of suspended animation that “could buy time for surgeons to stop the bleeding and save more of these patients.”
The technique has been done on at least six patients, though none were reported to survive. The trial is expected to include 20 people by the time it wraps up in December, according to the listing on the U.S. clinical trials database. Though given the strict requirements for candidates (emergency trauma victims who are not likely to survive), one can’t exactly rely on a set schedule.
Still, the technology is promising. Someday we may even use it to keep patients in suspended animation for months or years, experts predict, helping astronauts through decades-long spaceflights, or stalling death in sick patients awaiting a cure.
Artificial womb
Another sci-fi classic: growing human babies outside the womb. Think the fetus fields from “The Matrix,” or the frozen embryos in “Alien: Covenant.”
In 1923, British biologist J.B.S. Haldane coined a term for that – ectogenesis. He predicted that 70% of pregnancies would take place, from fertilization to birth, in artificial wombs by 2074. That many seems unlikely, but the timeline is on track.
Developing an embryo outside the womb is already routine in in vitro fertilization. And technology enables preterm babies to survive through much of the second half of gestation. Normal human pregnancy is 40 weeks, and the youngest preterm baby ever to survive was 21 weeks and 1 day old, just a few days younger than a smattering of others who lived.
The biggest obstacle for babies younger than that is lung viability. Mechanical ventilation can damage the lungs and lead to a chronic (sometimes fatal) lung disease known as bronchopulmonary dysplasia. Avoiding this would mean figuring out a way to maintain fetal circulation – the intricate system that delivers oxygenated blood from the placenta to the fetus via the umbilical cord. Researchers at Children’s Hospital of Philadelphia have done this using a fetal lamb.
The key to their invention is a substitute placenta: an oxygenator connected to the lamb’s umbilical cord. Tubes inserted through the umbilical vein and arteries carry oxygenated blood from the “placenta” to the fetus, and deoxygenated blood back out. The lamb resides in an artificial, fluid-filled amniotic sac until its lungs and other organs are developed.
Fertility treatment could benefit, too. “An artificial womb may substitute in situations in which a gestational carrier – surrogate – is indicated,” says Paula Amato, MD, a professor of obstetrics and gynecology at Oregon Health and Science University, Portland. (Dr. Amato is not involved in the CHOP research.) For example: when the mother is missing a uterus or can’t carry a pregnancy safely.
No date is set for clinical trials yet. But according to the research, the main difference between human and lamb may come down to size. A lamb’s umbilical vessels are larger, so feeding in a tube is easier. With today’s advances in miniaturizing surgical methods, that seems like a challenge scientists can overcome.
Messenger RNA therapeutics
Back to “Star Trek.” The hypospray injector’s contents could cure just about any disease, even one newly discovered on a strange planet. That’s not unlike messenger RNA (mRNA) technology, a breakthrough that enabled scientists to quickly develop some of the first COVID-19 vaccines.
But vaccines are just the beginning of what this technology can do.
A whole field of immunotherapy is emerging that uses mRNA to deliver instructions to produce chimeric antigen receptor–modified immune cells (CAR-modified immune cells). These cells are engineered to target diseased cells and tissues, like cancer cells and harmful fibroblasts (scar tissue) that promote fibrosis in, for example, the heart and lungs.
The field is bursting with rodent research, and clinical trials have started for treating some advanced-stage malignancies.
Actual clinical use may be years away, but if all goes well, these medicines could help treat or even cure the core medical problems facing humanity. We’re talking cancer, heart disease, neurodegenerative disease – transforming one therapy into another by simply changing the mRNA’s “nucleotide sequence,” the blueprint containing instructions telling it what to do, and what disease to attack.
As this technology matures, we may start to feel as if we’re really on “Star Trek,” where Dr. Leonard “Bones” McCoy pulls out the same device to treat just about every disease or injury.
A version of this article first appeared on WebMD.com.
Difficulty fitting family into career: Female oncologists
In a survey of just over 1,000 female oncologists, 95% said their career plans were at least somewhat associated with the timing of when to start a family.
The most striking finding was that one third of respondents had miscarried and another one third reported difficulty with infertility that required fertility counseling and/or treatment.
One third reported experiencing discrimination during pregnancy, and another third said they experienced discrimination for taking maternity leave, and having more than one child increased the likelihood of this.
The most common negative factor associated with family planning was long work hours and heavy workload (66.6%),
These findings suggest there are systemic changes needed not only in the healthcare setting but in society as a whole around women in the workplace and their choices of childbearing, say the authors.
The study was published online in JAMA Network Open and led by Anna Lee MD, MPH, from the department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston.
In an invited commentary, Mona Saleh, MD, and Stephanie Blank, MD, from the department of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai in New York, suggest that cultural changes are needed that go beyond women in medicine.
“These cultural values are so deeply pervasive (one could also say invasive) that they affect even these most educated and wealthy professional women, such as those who participated in this survey,” the editorialists write.
“[The researchers] advocate for early education on assisted reproductive technology (ART) risks, benefits, and success rates, but this is not getting at the underlying issue: Pregnancy discrimination and unfair distribution of childbearing responsibilities are a reflection of a larger problematic culture rather than an issue specific to women in medicine,” they add.
Survey details
The survey comprised a novel 39-item questionnaire distributed to 1,004 U.S. female oncologists from May 7 to June 30, 2020, via email and social media channels.
Most respondents (84.4%) were married, and 71% were currently working full-time.
About one-third (35%) worked in radiation oncology, another third (34.3%) in medical oncology, 18.4% in surgical oncology, and 9.1% in pediatric oncology.
A total of 768 respondents (76.5%) had children, and of these, 415 (41.3%) first gave birth during postgraduate training and 275 (27.4%) gave birth in years 1-5 as an attending physician.
Of all respondents who had been pregnant, approximately two-thirds (65.7%) had some type of pregnancy complication. About one-third of respondents (31.7%) reported having experienced a miscarriage after a confirmed pregnancy; of those, 61.6% reported one miscarriage, while the remainder had two or more miscarriages (38.4%).
Approximately one-third (31.4%) of respondents reported difficulty with infertility that required fertility counseling and/or treatment.
The questionnaire also asked about assisted reproductive technology, and 164 participants (16.3%) reported the use of fertility medications, and 53 (5.3%) reported cryopreservation of eggs. Nearly 13% reported the use of intrauterine insemination and 13.2% reported the use of in vivo fertilization. Among those who experienced fertility concerns, 36.6% (232 of 634) reported facing financial burdens because of fertility or pregnancy that was in some way associated with their career choice.
When asked on the survey if fertility preservation should be discussed with women during medical school and/or residency, 65.7% of respondents stated that it should.
However, the editorialists suggest that “encouraging formal and directed education regarding the infertility risks specifically toward female physicians (which Lee et al. recommend) could be perceived as a blanket recommendation that it is best for women in medicine to delay childbearing and pursue ART.”
“Medical schools and residency and fellowship training programs should instead focus their energy on creating a framework and culture that normalizes conception during these points in training while also subsidizing and supporting trainees and physicians who prefer to use ART and delay fertility until after training,” they suggest.
The editorialists also emphasized that women may choose to become pregnant at any point during the years that it takes to go from being a medical student to resident/fellow to attending physician, and they should be supported by their workplace on their decisions.
The study was funded by grants from National Institutes of Health/National Cancer Institute Cancer Center.
Dr. Lee and coauthors reported no relevant financial relationships. Dr. Blank reported receiving grants from AstraZeneca, Aravive, Akesobio, GlaxoSmithKline, Merck, and Seattle Genetics outside the submitted work. Dr. Saleh reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a survey of just over 1,000 female oncologists, 95% said their career plans were at least somewhat associated with the timing of when to start a family.
The most striking finding was that one third of respondents had miscarried and another one third reported difficulty with infertility that required fertility counseling and/or treatment.
One third reported experiencing discrimination during pregnancy, and another third said they experienced discrimination for taking maternity leave, and having more than one child increased the likelihood of this.
The most common negative factor associated with family planning was long work hours and heavy workload (66.6%),
These findings suggest there are systemic changes needed not only in the healthcare setting but in society as a whole around women in the workplace and their choices of childbearing, say the authors.
The study was published online in JAMA Network Open and led by Anna Lee MD, MPH, from the department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston.
In an invited commentary, Mona Saleh, MD, and Stephanie Blank, MD, from the department of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai in New York, suggest that cultural changes are needed that go beyond women in medicine.
“These cultural values are so deeply pervasive (one could also say invasive) that they affect even these most educated and wealthy professional women, such as those who participated in this survey,” the editorialists write.
“[The researchers] advocate for early education on assisted reproductive technology (ART) risks, benefits, and success rates, but this is not getting at the underlying issue: Pregnancy discrimination and unfair distribution of childbearing responsibilities are a reflection of a larger problematic culture rather than an issue specific to women in medicine,” they add.
Survey details
The survey comprised a novel 39-item questionnaire distributed to 1,004 U.S. female oncologists from May 7 to June 30, 2020, via email and social media channels.
Most respondents (84.4%) were married, and 71% were currently working full-time.
About one-third (35%) worked in radiation oncology, another third (34.3%) in medical oncology, 18.4% in surgical oncology, and 9.1% in pediatric oncology.
A total of 768 respondents (76.5%) had children, and of these, 415 (41.3%) first gave birth during postgraduate training and 275 (27.4%) gave birth in years 1-5 as an attending physician.
Of all respondents who had been pregnant, approximately two-thirds (65.7%) had some type of pregnancy complication. About one-third of respondents (31.7%) reported having experienced a miscarriage after a confirmed pregnancy; of those, 61.6% reported one miscarriage, while the remainder had two or more miscarriages (38.4%).
Approximately one-third (31.4%) of respondents reported difficulty with infertility that required fertility counseling and/or treatment.
The questionnaire also asked about assisted reproductive technology, and 164 participants (16.3%) reported the use of fertility medications, and 53 (5.3%) reported cryopreservation of eggs. Nearly 13% reported the use of intrauterine insemination and 13.2% reported the use of in vivo fertilization. Among those who experienced fertility concerns, 36.6% (232 of 634) reported facing financial burdens because of fertility or pregnancy that was in some way associated with their career choice.
When asked on the survey if fertility preservation should be discussed with women during medical school and/or residency, 65.7% of respondents stated that it should.
However, the editorialists suggest that “encouraging formal and directed education regarding the infertility risks specifically toward female physicians (which Lee et al. recommend) could be perceived as a blanket recommendation that it is best for women in medicine to delay childbearing and pursue ART.”
“Medical schools and residency and fellowship training programs should instead focus their energy on creating a framework and culture that normalizes conception during these points in training while also subsidizing and supporting trainees and physicians who prefer to use ART and delay fertility until after training,” they suggest.
The editorialists also emphasized that women may choose to become pregnant at any point during the years that it takes to go from being a medical student to resident/fellow to attending physician, and they should be supported by their workplace on their decisions.
The study was funded by grants from National Institutes of Health/National Cancer Institute Cancer Center.
Dr. Lee and coauthors reported no relevant financial relationships. Dr. Blank reported receiving grants from AstraZeneca, Aravive, Akesobio, GlaxoSmithKline, Merck, and Seattle Genetics outside the submitted work. Dr. Saleh reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a survey of just over 1,000 female oncologists, 95% said their career plans were at least somewhat associated with the timing of when to start a family.
The most striking finding was that one third of respondents had miscarried and another one third reported difficulty with infertility that required fertility counseling and/or treatment.
One third reported experiencing discrimination during pregnancy, and another third said they experienced discrimination for taking maternity leave, and having more than one child increased the likelihood of this.
The most common negative factor associated with family planning was long work hours and heavy workload (66.6%),
These findings suggest there are systemic changes needed not only in the healthcare setting but in society as a whole around women in the workplace and their choices of childbearing, say the authors.
The study was published online in JAMA Network Open and led by Anna Lee MD, MPH, from the department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston.
In an invited commentary, Mona Saleh, MD, and Stephanie Blank, MD, from the department of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai in New York, suggest that cultural changes are needed that go beyond women in medicine.
“These cultural values are so deeply pervasive (one could also say invasive) that they affect even these most educated and wealthy professional women, such as those who participated in this survey,” the editorialists write.
“[The researchers] advocate for early education on assisted reproductive technology (ART) risks, benefits, and success rates, but this is not getting at the underlying issue: Pregnancy discrimination and unfair distribution of childbearing responsibilities are a reflection of a larger problematic culture rather than an issue specific to women in medicine,” they add.
Survey details
The survey comprised a novel 39-item questionnaire distributed to 1,004 U.S. female oncologists from May 7 to June 30, 2020, via email and social media channels.
Most respondents (84.4%) were married, and 71% were currently working full-time.
About one-third (35%) worked in radiation oncology, another third (34.3%) in medical oncology, 18.4% in surgical oncology, and 9.1% in pediatric oncology.
A total of 768 respondents (76.5%) had children, and of these, 415 (41.3%) first gave birth during postgraduate training and 275 (27.4%) gave birth in years 1-5 as an attending physician.
Of all respondents who had been pregnant, approximately two-thirds (65.7%) had some type of pregnancy complication. About one-third of respondents (31.7%) reported having experienced a miscarriage after a confirmed pregnancy; of those, 61.6% reported one miscarriage, while the remainder had two or more miscarriages (38.4%).
Approximately one-third (31.4%) of respondents reported difficulty with infertility that required fertility counseling and/or treatment.
The questionnaire also asked about assisted reproductive technology, and 164 participants (16.3%) reported the use of fertility medications, and 53 (5.3%) reported cryopreservation of eggs. Nearly 13% reported the use of intrauterine insemination and 13.2% reported the use of in vivo fertilization. Among those who experienced fertility concerns, 36.6% (232 of 634) reported facing financial burdens because of fertility or pregnancy that was in some way associated with their career choice.
When asked on the survey if fertility preservation should be discussed with women during medical school and/or residency, 65.7% of respondents stated that it should.
However, the editorialists suggest that “encouraging formal and directed education regarding the infertility risks specifically toward female physicians (which Lee et al. recommend) could be perceived as a blanket recommendation that it is best for women in medicine to delay childbearing and pursue ART.”
“Medical schools and residency and fellowship training programs should instead focus their energy on creating a framework and culture that normalizes conception during these points in training while also subsidizing and supporting trainees and physicians who prefer to use ART and delay fertility until after training,” they suggest.
The editorialists also emphasized that women may choose to become pregnant at any point during the years that it takes to go from being a medical student to resident/fellow to attending physician, and they should be supported by their workplace on their decisions.
The study was funded by grants from National Institutes of Health/National Cancer Institute Cancer Center.
Dr. Lee and coauthors reported no relevant financial relationships. Dr. Blank reported receiving grants from AstraZeneca, Aravive, Akesobio, GlaxoSmithKline, Merck, and Seattle Genetics outside the submitted work. Dr. Saleh reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Women with cycle disorders across their life span may be at increased risk of cardiovascular disease
This finding is demonstrated in a new analysis of the Nurses’ Health Study II.
“To date, several studies have reported increased risks of cardiovascular risk factors or cardiovascular disease in connection with cycle disorders,” Yi-Xin Wang, MD, PhD, a research fellow in nutrition, and associates from the Harvard School of Public Health, Boston, wrote in an article published in JAMA Network Open.
Ute Seeland, MD, speaker of the Gender Medicine in Cardiology Working Group of the German Cardiology Society, said in an interview“We know that women who have indicated in their medical history that they have irregular menstrual cycles, invariably in connection with polycystic ovary syndrome (PCOS), more commonly develop diabetes and other metabolic disorders, as well as cardiovascular diseases.”
Cycle disorders’ role
However, the role that irregular or especially long cycles play at different points of a woman’s reproductive life span was unclear. Therefore, the research group investigated the associations in the Nurses’ Health Study II between cycle irregularity and cycle length in women of different age groups who later experienced cardiovascular events.
At the end of this study in 1989, the participants also provided information regarding the length and irregularity of their menstrual cycle from ages 14 to 17 years and again from ages 18 to 22 years. The information was updated in 1993 when the participants were aged 29-46 years. The data from 2019 to 2022 were analyzed.
“This kind of long-term cohort study is extremely rare and therefore something special,” said Dr. Seeland, who conducts research at the Institute for Social Medicine, Epidemiology, and Health Economics at the Charité – University Hospital Berlin.
The investigators used the following cycle classifications: very regular (no more than 3 or 4 days before or after the expected date), regular (within 5-7 days), usually irregular, always irregular, or no periods.
The cycle lengths were divided into the following categories: less than 21 days, 21-25 days, 26-31 days, 32-39 days, 40-50 days, more than 50 days, and too irregular to estimate the length.
The onset of cardiovascular diseases was determined using information from the participants and was confirmed by reviewing the medical files. Relevant to the study were lethal and nonlethal coronary heart diseases (such as myocardial infarction or coronary artery revascularization), as well as strokes.
Significant in adulthood
The data from 80,630 study participants were included in the analysis. At study inclusion, the average age of the participants was 37.7 years, and the average body mass index (BMI) was 25.1. “Since it was predominantly White nurses who took part in the study, the data are not transferable to other, more diverse populations,” said Dr. Seeland.
Over 24 years, 1,816 women (2.4%) had a cardiovascular event. “We observed an increased rate of cardiovascular events in women with an irregular cycle and longer cycle, both in early an in mid-adulthood,” wrote Dr. Wang and associates. “Similar trends were also observed for cycle disorders when younger, but this association was weaker than in adulthood.”
Compared with women with very regular cycles, women with irregular cycles or without periods who were aged 14-17 years, 18-22 years, or 29-49 years exhibited a 15%, 36%, and 40% higher risk of a cardiovascular event, respectively.
Similarly, women aged 18-22 years or 29-46 years with long cycles of 40 days or more had a 44% or 30% higher risk of cardiovascular disease, respectively, compared with women with cycle lengths of 26-31 days.
“The coronary heart diseases were decisive for the increase, and less so, the strokes,” wrote the researchers.
Classic risk factors?
Dr. Seeland praised the fact that the study authors tried to determine the role that classic cardiovascular risk factors played. “Compared with women with a regular cycle, women with an irregular cycle had a higher BMI, more frequently increased cholesterol levels, and an elevated blood pressure,” she said. Women with a long cycle displayed a similar pattern.
It can be assumed from this that over a woman’s life span, BMI affects the risk of cardiovascular disease. Therefore, Dr. Wang and coauthors adjusted the results on the basis of BMI, which varies over time.
Regarding other classic risk factors that may have played a role, “hypercholesterolemia, chronic high blood pressure, and type 2 diabetes were only responsible in 5.4%-13.5% of the associations,” wrote the researchers.
“Our results suggest that certain characteristics of the menstrual cycle across a woman’s reproductive lifespan may constitute additional risk markers for cardiovascular disease,” according to the authors.
The highest rates of cardiovascular disease were among women with permanently irregular or long cycles in early to mid adulthood, as well as women who had regular cycles when younger but had irregular cycles in mid adulthood. “This indicates that the change from one cycle phenotype to another could be a surrogate marker for metabolic changes, which in turn contribute to the formation of cardiovascular diseases,” wrote the authors.
The study was observational and so conclusions cannot be drawn regarding causal relationships. But Dr. Wang and associates indicate that the most common cause of an irregular menstrual cycle may be PCOS. “Roughly 90% of women with cycle disorders or oligomenorrhea have signs of PCOS. And it was shown that women with PCOS have an increased risk of cardiovascular disease.”
They concluded that “the associations observed between irregular and long cycles in early to mid-adulthood and cardiovascular diseases are likely attributable to underlying PCOS.”
For Dr. Seeland, however, this conclusion is “too monocausal. At no point in time did there seem to be any direct information regarding the frequency of PCOS during the data collection by the respondents.”
For now, we can only speculate about the mechanisms. “The association between a very irregular and long cycle and the increased risk of cardiovascular diseases has now only been described. More research should be done on the causes,” said Dr. Seeland.
This article was translated from the Medscape German edition. A version of this article first appeared on Medscape.com.
This finding is demonstrated in a new analysis of the Nurses’ Health Study II.
“To date, several studies have reported increased risks of cardiovascular risk factors or cardiovascular disease in connection with cycle disorders,” Yi-Xin Wang, MD, PhD, a research fellow in nutrition, and associates from the Harvard School of Public Health, Boston, wrote in an article published in JAMA Network Open.
Ute Seeland, MD, speaker of the Gender Medicine in Cardiology Working Group of the German Cardiology Society, said in an interview“We know that women who have indicated in their medical history that they have irregular menstrual cycles, invariably in connection with polycystic ovary syndrome (PCOS), more commonly develop diabetes and other metabolic disorders, as well as cardiovascular diseases.”
Cycle disorders’ role
However, the role that irregular or especially long cycles play at different points of a woman’s reproductive life span was unclear. Therefore, the research group investigated the associations in the Nurses’ Health Study II between cycle irregularity and cycle length in women of different age groups who later experienced cardiovascular events.
At the end of this study in 1989, the participants also provided information regarding the length and irregularity of their menstrual cycle from ages 14 to 17 years and again from ages 18 to 22 years. The information was updated in 1993 when the participants were aged 29-46 years. The data from 2019 to 2022 were analyzed.
“This kind of long-term cohort study is extremely rare and therefore something special,” said Dr. Seeland, who conducts research at the Institute for Social Medicine, Epidemiology, and Health Economics at the Charité – University Hospital Berlin.
The investigators used the following cycle classifications: very regular (no more than 3 or 4 days before or after the expected date), regular (within 5-7 days), usually irregular, always irregular, or no periods.
The cycle lengths were divided into the following categories: less than 21 days, 21-25 days, 26-31 days, 32-39 days, 40-50 days, more than 50 days, and too irregular to estimate the length.
The onset of cardiovascular diseases was determined using information from the participants and was confirmed by reviewing the medical files. Relevant to the study were lethal and nonlethal coronary heart diseases (such as myocardial infarction or coronary artery revascularization), as well as strokes.
Significant in adulthood
The data from 80,630 study participants were included in the analysis. At study inclusion, the average age of the participants was 37.7 years, and the average body mass index (BMI) was 25.1. “Since it was predominantly White nurses who took part in the study, the data are not transferable to other, more diverse populations,” said Dr. Seeland.
Over 24 years, 1,816 women (2.4%) had a cardiovascular event. “We observed an increased rate of cardiovascular events in women with an irregular cycle and longer cycle, both in early an in mid-adulthood,” wrote Dr. Wang and associates. “Similar trends were also observed for cycle disorders when younger, but this association was weaker than in adulthood.”
Compared with women with very regular cycles, women with irregular cycles or without periods who were aged 14-17 years, 18-22 years, or 29-49 years exhibited a 15%, 36%, and 40% higher risk of a cardiovascular event, respectively.
Similarly, women aged 18-22 years or 29-46 years with long cycles of 40 days or more had a 44% or 30% higher risk of cardiovascular disease, respectively, compared with women with cycle lengths of 26-31 days.
“The coronary heart diseases were decisive for the increase, and less so, the strokes,” wrote the researchers.
Classic risk factors?
Dr. Seeland praised the fact that the study authors tried to determine the role that classic cardiovascular risk factors played. “Compared with women with a regular cycle, women with an irregular cycle had a higher BMI, more frequently increased cholesterol levels, and an elevated blood pressure,” she said. Women with a long cycle displayed a similar pattern.
It can be assumed from this that over a woman’s life span, BMI affects the risk of cardiovascular disease. Therefore, Dr. Wang and coauthors adjusted the results on the basis of BMI, which varies over time.
Regarding other classic risk factors that may have played a role, “hypercholesterolemia, chronic high blood pressure, and type 2 diabetes were only responsible in 5.4%-13.5% of the associations,” wrote the researchers.
“Our results suggest that certain characteristics of the menstrual cycle across a woman’s reproductive lifespan may constitute additional risk markers for cardiovascular disease,” according to the authors.
The highest rates of cardiovascular disease were among women with permanently irregular or long cycles in early to mid adulthood, as well as women who had regular cycles when younger but had irregular cycles in mid adulthood. “This indicates that the change from one cycle phenotype to another could be a surrogate marker for metabolic changes, which in turn contribute to the formation of cardiovascular diseases,” wrote the authors.
The study was observational and so conclusions cannot be drawn regarding causal relationships. But Dr. Wang and associates indicate that the most common cause of an irregular menstrual cycle may be PCOS. “Roughly 90% of women with cycle disorders or oligomenorrhea have signs of PCOS. And it was shown that women with PCOS have an increased risk of cardiovascular disease.”
They concluded that “the associations observed between irregular and long cycles in early to mid-adulthood and cardiovascular diseases are likely attributable to underlying PCOS.”
For Dr. Seeland, however, this conclusion is “too monocausal. At no point in time did there seem to be any direct information regarding the frequency of PCOS during the data collection by the respondents.”
For now, we can only speculate about the mechanisms. “The association between a very irregular and long cycle and the increased risk of cardiovascular diseases has now only been described. More research should be done on the causes,” said Dr. Seeland.
This article was translated from the Medscape German edition. A version of this article first appeared on Medscape.com.
This finding is demonstrated in a new analysis of the Nurses’ Health Study II.
“To date, several studies have reported increased risks of cardiovascular risk factors or cardiovascular disease in connection with cycle disorders,” Yi-Xin Wang, MD, PhD, a research fellow in nutrition, and associates from the Harvard School of Public Health, Boston, wrote in an article published in JAMA Network Open.
Ute Seeland, MD, speaker of the Gender Medicine in Cardiology Working Group of the German Cardiology Society, said in an interview“We know that women who have indicated in their medical history that they have irregular menstrual cycles, invariably in connection with polycystic ovary syndrome (PCOS), more commonly develop diabetes and other metabolic disorders, as well as cardiovascular diseases.”
Cycle disorders’ role
However, the role that irregular or especially long cycles play at different points of a woman’s reproductive life span was unclear. Therefore, the research group investigated the associations in the Nurses’ Health Study II between cycle irregularity and cycle length in women of different age groups who later experienced cardiovascular events.
At the end of this study in 1989, the participants also provided information regarding the length and irregularity of their menstrual cycle from ages 14 to 17 years and again from ages 18 to 22 years. The information was updated in 1993 when the participants were aged 29-46 years. The data from 2019 to 2022 were analyzed.
“This kind of long-term cohort study is extremely rare and therefore something special,” said Dr. Seeland, who conducts research at the Institute for Social Medicine, Epidemiology, and Health Economics at the Charité – University Hospital Berlin.
The investigators used the following cycle classifications: very regular (no more than 3 or 4 days before or after the expected date), regular (within 5-7 days), usually irregular, always irregular, or no periods.
The cycle lengths were divided into the following categories: less than 21 days, 21-25 days, 26-31 days, 32-39 days, 40-50 days, more than 50 days, and too irregular to estimate the length.
The onset of cardiovascular diseases was determined using information from the participants and was confirmed by reviewing the medical files. Relevant to the study were lethal and nonlethal coronary heart diseases (such as myocardial infarction or coronary artery revascularization), as well as strokes.
Significant in adulthood
The data from 80,630 study participants were included in the analysis. At study inclusion, the average age of the participants was 37.7 years, and the average body mass index (BMI) was 25.1. “Since it was predominantly White nurses who took part in the study, the data are not transferable to other, more diverse populations,” said Dr. Seeland.
Over 24 years, 1,816 women (2.4%) had a cardiovascular event. “We observed an increased rate of cardiovascular events in women with an irregular cycle and longer cycle, both in early an in mid-adulthood,” wrote Dr. Wang and associates. “Similar trends were also observed for cycle disorders when younger, but this association was weaker than in adulthood.”
Compared with women with very regular cycles, women with irregular cycles or without periods who were aged 14-17 years, 18-22 years, or 29-49 years exhibited a 15%, 36%, and 40% higher risk of a cardiovascular event, respectively.
Similarly, women aged 18-22 years or 29-46 years with long cycles of 40 days or more had a 44% or 30% higher risk of cardiovascular disease, respectively, compared with women with cycle lengths of 26-31 days.
“The coronary heart diseases were decisive for the increase, and less so, the strokes,” wrote the researchers.
Classic risk factors?
Dr. Seeland praised the fact that the study authors tried to determine the role that classic cardiovascular risk factors played. “Compared with women with a regular cycle, women with an irregular cycle had a higher BMI, more frequently increased cholesterol levels, and an elevated blood pressure,” she said. Women with a long cycle displayed a similar pattern.
It can be assumed from this that over a woman’s life span, BMI affects the risk of cardiovascular disease. Therefore, Dr. Wang and coauthors adjusted the results on the basis of BMI, which varies over time.
Regarding other classic risk factors that may have played a role, “hypercholesterolemia, chronic high blood pressure, and type 2 diabetes were only responsible in 5.4%-13.5% of the associations,” wrote the researchers.
“Our results suggest that certain characteristics of the menstrual cycle across a woman’s reproductive lifespan may constitute additional risk markers for cardiovascular disease,” according to the authors.
The highest rates of cardiovascular disease were among women with permanently irregular or long cycles in early to mid adulthood, as well as women who had regular cycles when younger but had irregular cycles in mid adulthood. “This indicates that the change from one cycle phenotype to another could be a surrogate marker for metabolic changes, which in turn contribute to the formation of cardiovascular diseases,” wrote the authors.
The study was observational and so conclusions cannot be drawn regarding causal relationships. But Dr. Wang and associates indicate that the most common cause of an irregular menstrual cycle may be PCOS. “Roughly 90% of women with cycle disorders or oligomenorrhea have signs of PCOS. And it was shown that women with PCOS have an increased risk of cardiovascular disease.”
They concluded that “the associations observed between irregular and long cycles in early to mid-adulthood and cardiovascular diseases are likely attributable to underlying PCOS.”
For Dr. Seeland, however, this conclusion is “too monocausal. At no point in time did there seem to be any direct information regarding the frequency of PCOS during the data collection by the respondents.”
For now, we can only speculate about the mechanisms. “The association between a very irregular and long cycle and the increased risk of cardiovascular diseases has now only been described. More research should be done on the causes,” said Dr. Seeland.
This article was translated from the Medscape German edition. A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Endometrial receptivity testing before IVF seen as unnecessary
Endometrial receptivity testing (ERT) did not increase the chances of achieving live birth in patients undergoing in vitro fertilization.
The study was promoted by widespread use of the tests in reproductive medicine and earlier conflicting studies regarding its effectiveness. The procedure, in which doctors extract cells from a woman’s endometrial lining in an effort to determine the best day to perform in vitro fertilization, requires a biopsy, can take a month to generate results, and costs up to $1,000.
But the new study, published online December 6 in the Journal of the American Medical Association, found that embryo transfer based on the timing of ERT was no better than that based on the standard protocol.
“Endometrial receptivity testing ended up not being beneficial in the population of interest, a good-prognosis IVF patient population,” said Nicole Doyle, MD, PhD, of Shady Grove Fertility, in Arlington, Va., who led the study. “For this particular patient population I would not recommend ERT based on the results of the trial.”
“Unfortunately, as is our history in reproductive medicine, we may embrace technology prematurely given patient desperation and physician eagerness to improve pregnancy outcomes,” said Mark P. Trolice, MD, director of the IVF Center in Orlando, who was not involved in the new research.
The double-blind, randomized clinical trial enrolled 726 women treated at Dr. Doyle’s clinic between May 2018 and September 2020.
All the women underwent ERT. Of those who received adjusted progesterone exposure after the test, live birth occurred in 58.5% of transfers (223 of 381). Among those in a control group who did not have their progesterone adjusted after ERT and underwent IVF on a standardized schedule, 61.9% of transfers (239 of 386) resulted in live birth, according to the researchers.
The differences in rates of clinical (77.2% vs. 79.5% [95% confidence interval, −10.4% to 2.4%]) and biochemical pregnancy (68.8% vs. 72.8% [95% CI, −8.2% to 3.5%]) were not statistically significant between the two groups, Dr. Doyle and her colleagues reported.
Women who experienced recurrent implantation failure (RIF), defined as more than two failed embryo transfers, were excluded from the study. “We can’t assess the benefit of an endometrial receptivity testing in this particular patient population,” Dr. Doyle said.
However, she noted that the number of women who undergo RIF is “a very small fraction of all IVF patients, less than 5%.” Of those, half are expected to have embryos that are not suitable for implantation, Dr. Doyle said.
As a result, she said, “it’s really only about 2.5% of IVF patients for which we don’t yet have an answer regarding the utility of ERT.”
Dr. Trolice, also a professor at the University of Central Florida, Orlando, expressed certainty that the “one-size-fits-all approach” for ERT has been disproven by the study’s failure to find a benefit from the procedure in women with a “good prognosis.” But, he added, whether ERT is of value in a subset of patients, such as those with recurrent implantation failure, remains “a question of vital importance.”
Dr. Doyle and Dr. Trolice reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Endometrial receptivity testing (ERT) did not increase the chances of achieving live birth in patients undergoing in vitro fertilization.
The study was promoted by widespread use of the tests in reproductive medicine and earlier conflicting studies regarding its effectiveness. The procedure, in which doctors extract cells from a woman’s endometrial lining in an effort to determine the best day to perform in vitro fertilization, requires a biopsy, can take a month to generate results, and costs up to $1,000.
But the new study, published online December 6 in the Journal of the American Medical Association, found that embryo transfer based on the timing of ERT was no better than that based on the standard protocol.
“Endometrial receptivity testing ended up not being beneficial in the population of interest, a good-prognosis IVF patient population,” said Nicole Doyle, MD, PhD, of Shady Grove Fertility, in Arlington, Va., who led the study. “For this particular patient population I would not recommend ERT based on the results of the trial.”
“Unfortunately, as is our history in reproductive medicine, we may embrace technology prematurely given patient desperation and physician eagerness to improve pregnancy outcomes,” said Mark P. Trolice, MD, director of the IVF Center in Orlando, who was not involved in the new research.
The double-blind, randomized clinical trial enrolled 726 women treated at Dr. Doyle’s clinic between May 2018 and September 2020.
All the women underwent ERT. Of those who received adjusted progesterone exposure after the test, live birth occurred in 58.5% of transfers (223 of 381). Among those in a control group who did not have their progesterone adjusted after ERT and underwent IVF on a standardized schedule, 61.9% of transfers (239 of 386) resulted in live birth, according to the researchers.
The differences in rates of clinical (77.2% vs. 79.5% [95% confidence interval, −10.4% to 2.4%]) and biochemical pregnancy (68.8% vs. 72.8% [95% CI, −8.2% to 3.5%]) were not statistically significant between the two groups, Dr. Doyle and her colleagues reported.
Women who experienced recurrent implantation failure (RIF), defined as more than two failed embryo transfers, were excluded from the study. “We can’t assess the benefit of an endometrial receptivity testing in this particular patient population,” Dr. Doyle said.
However, she noted that the number of women who undergo RIF is “a very small fraction of all IVF patients, less than 5%.” Of those, half are expected to have embryos that are not suitable for implantation, Dr. Doyle said.
As a result, she said, “it’s really only about 2.5% of IVF patients for which we don’t yet have an answer regarding the utility of ERT.”
Dr. Trolice, also a professor at the University of Central Florida, Orlando, expressed certainty that the “one-size-fits-all approach” for ERT has been disproven by the study’s failure to find a benefit from the procedure in women with a “good prognosis.” But, he added, whether ERT is of value in a subset of patients, such as those with recurrent implantation failure, remains “a question of vital importance.”
Dr. Doyle and Dr. Trolice reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Endometrial receptivity testing (ERT) did not increase the chances of achieving live birth in patients undergoing in vitro fertilization.
The study was promoted by widespread use of the tests in reproductive medicine and earlier conflicting studies regarding its effectiveness. The procedure, in which doctors extract cells from a woman’s endometrial lining in an effort to determine the best day to perform in vitro fertilization, requires a biopsy, can take a month to generate results, and costs up to $1,000.
But the new study, published online December 6 in the Journal of the American Medical Association, found that embryo transfer based on the timing of ERT was no better than that based on the standard protocol.
“Endometrial receptivity testing ended up not being beneficial in the population of interest, a good-prognosis IVF patient population,” said Nicole Doyle, MD, PhD, of Shady Grove Fertility, in Arlington, Va., who led the study. “For this particular patient population I would not recommend ERT based on the results of the trial.”
“Unfortunately, as is our history in reproductive medicine, we may embrace technology prematurely given patient desperation and physician eagerness to improve pregnancy outcomes,” said Mark P. Trolice, MD, director of the IVF Center in Orlando, who was not involved in the new research.
The double-blind, randomized clinical trial enrolled 726 women treated at Dr. Doyle’s clinic between May 2018 and September 2020.
All the women underwent ERT. Of those who received adjusted progesterone exposure after the test, live birth occurred in 58.5% of transfers (223 of 381). Among those in a control group who did not have their progesterone adjusted after ERT and underwent IVF on a standardized schedule, 61.9% of transfers (239 of 386) resulted in live birth, according to the researchers.
The differences in rates of clinical (77.2% vs. 79.5% [95% confidence interval, −10.4% to 2.4%]) and biochemical pregnancy (68.8% vs. 72.8% [95% CI, −8.2% to 3.5%]) were not statistically significant between the two groups, Dr. Doyle and her colleagues reported.
Women who experienced recurrent implantation failure (RIF), defined as more than two failed embryo transfers, were excluded from the study. “We can’t assess the benefit of an endometrial receptivity testing in this particular patient population,” Dr. Doyle said.
However, she noted that the number of women who undergo RIF is “a very small fraction of all IVF patients, less than 5%.” Of those, half are expected to have embryos that are not suitable for implantation, Dr. Doyle said.
As a result, she said, “it’s really only about 2.5% of IVF patients for which we don’t yet have an answer regarding the utility of ERT.”
Dr. Trolice, also a professor at the University of Central Florida, Orlando, expressed certainty that the “one-size-fits-all approach” for ERT has been disproven by the study’s failure to find a benefit from the procedure in women with a “good prognosis.” But, he added, whether ERT is of value in a subset of patients, such as those with recurrent implantation failure, remains “a question of vital importance.”
Dr. Doyle and Dr. Trolice reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA