Pain

Women with endometriosis have a much higher risk of being diagnosed with several psychiatric disorders during the postpartum period according to an oral abstract presented at the American Society for Reproductive Medicine’s 2024 Scientific Congress and Expo in Denver, Colorado.

Researchers compared rates of postpartum depression, anxiety, mood disturbance (temporary low or anxious mood requiring no treatment), and obsessive-compulsive disorder (OCD) diagnoses among over 200 million adult women from 67 healthcare organizations who had a child between 2005 and 2023.

Within a year after giving birth, women with prepregnancy endometriosis were 25% more likely to be diagnosed with postpartum depression, 85% more likely to be diagnosed with postpartum mood disturbance, 44% more likely to be diagnosed with anxiety, and 1.26 times more likely to be diagnosed with OCD.

About 75% of women studied had no preexisting depression. This population had a 17% higher risk of receiving a postpartum depression diagnosis, a 95% higher risk of receiving an OCD diagnosis, a 72% higher risk of receiving a postpartum mood disturbance diagnosis, and a 38% risk of receiving an anxiety diagnosis.

Among women without preexisting depression, the risk increased by 64% for OCD, 42% for postpartum mood disturbance, and 25% for anxiety, while the risk for postpartum depression was negligible, indicating that women already experiencing depression likely have a higher baseline risk for worsening symptoms postpartum, said the study’s lead author Tina Yi-Jin Hsieh, MD, MPH, biomedical researcher at Harvard Medical School in Boston, Massachusetts.

“We think that because preexisting depression is the more dominant risk factor, it doesn’t really matter if you have another additional risk factor like endometriosis to really change the risk of postpartum depression,” said Hsieh.

Endometriosis is a debilitating condition in which tissue similar to uterine lining grows on the outside of the uterus, causing chronic pain and infertility. It affects between 6% and 10% of women worldwide and takes an average of between 4 and 11 years to be diagnosed. It has been linked to depression and anxiety disorders, yet the study authors say there’s little research examining its impact on women in the year after giving birth.

“Endometriosis is a complex condition that can affect both physical and mental health over much of a person’s life,” said Anna Modest, PhD, assistant professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School and a study author. “Perinatal and maternal mental health can have a huge impact on children and their family — we need to better understand who is at risk for challenges in the postpartum period.”

“Most chronic medical illnesses, particularly those causing pain, have been shown to increase the risk of mood disorders,” said Ripal Shah, MD, MPH, clinical associate professor of Psychiatry and Behavioral Sciences at Stanford Medicine in California. Shah specializes in reproductive psychiatry and was not associated with the study.

“What’s interesting about endometriosis though is that genome-wide association studies have shown that there may be a genetic predisposition for some women to develop both endometriosis and a mood disorder,” said Shah.

A 2023 study suggested that endometriosis, anxiety, and depression may be connected through a shared genetic basis.

But the experience patients with endometriosis go through also lends itself to the development of mood disorders, said Daniel Ginn, DO, assistant clinical professor of Obstetrics and Gynecology at the David Geffen School of Medicine at the University of California, Los Angeles. Ginn specializes in the treatment of endometriosis and was not a part of the study.

Beyond postpartum depression, Ginn wasn’t surprised by the association of endometriosis with anxiety or OCD because what he hears from patients “on a daily basis is the telling of a history that has been hallmarked by not being listened to, not being believed, and not having symptoms managed well.”

As a result, he said many patients focus heavily on learning about their condition, coming into office visits with binders full of test results and information in an effort to understand and manage it themselves. This “does lead to a certain sense of a need to grasp for control because no one else is helping them [treat their condition effectively].”

He added: “I find it hard to believe that anxiety and OCD were preexisting of the conditions rather than the consequence of a long-term suboptimally managed disease.”

The authors reported no disclosures or sources of funding.

A version of this article first appeared on Medscape.com.

Women with endometriosis have a much higher risk of being diagnosed with several psychiatric disorders during the postpartum period according to an oral abstract presented at the American Society for Reproductive Medicine’s 2024 Scientific Congress and Expo in Denver, Colorado.

Researchers compared rates of postpartum depression, anxiety, mood disturbance (temporary low or anxious mood requiring no treatment), and obsessive-compulsive disorder (OCD) diagnoses among over 200 million adult women from 67 healthcare organizations who had a child between 2005 and 2023.

Within a year after giving birth, women with prepregnancy endometriosis were 25% more likely to be diagnosed with postpartum depression, 85% more likely to be diagnosed with postpartum mood disturbance, 44% more likely to be diagnosed with anxiety, and 1.26 times more likely to be diagnosed with OCD.

About 75% of women studied had no preexisting depression. This population had a 17% higher risk of receiving a postpartum depression diagnosis, a 95% higher risk of receiving an OCD diagnosis, a 72% higher risk of receiving a postpartum mood disturbance diagnosis, and a 38% risk of receiving an anxiety diagnosis.

Among women without preexisting depression, the risk increased by 64% for OCD, 42% for postpartum mood disturbance, and 25% for anxiety, while the risk for postpartum depression was negligible, indicating that women already experiencing depression likely have a higher baseline risk for worsening symptoms postpartum, said the study’s lead author Tina Yi-Jin Hsieh, MD, MPH, biomedical researcher at Harvard Medical School in Boston, Massachusetts.

“We think that because preexisting depression is the more dominant risk factor, it doesn’t really matter if you have another additional risk factor like endometriosis to really change the risk of postpartum depression,” said Hsieh.

Endometriosis is a debilitating condition in which tissue similar to uterine lining grows on the outside of the uterus, causing chronic pain and infertility. It affects between 6% and 10% of women worldwide and takes an average of between 4 and 11 years to be diagnosed. It has been linked to depression and anxiety disorders, yet the study authors say there’s little research examining its impact on women in the year after giving birth.

“Endometriosis is a complex condition that can affect both physical and mental health over much of a person’s life,” said Anna Modest, PhD, assistant professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School and a study author. “Perinatal and maternal mental health can have a huge impact on children and their family — we need to better understand who is at risk for challenges in the postpartum period.”

“Most chronic medical illnesses, particularly those causing pain, have been shown to increase the risk of mood disorders,” said Ripal Shah, MD, MPH, clinical associate professor of Psychiatry and Behavioral Sciences at Stanford Medicine in California. Shah specializes in reproductive psychiatry and was not associated with the study.

“What’s interesting about endometriosis though is that genome-wide association studies have shown that there may be a genetic predisposition for some women to develop both endometriosis and a mood disorder,” said Shah.

A 2023 study suggested that endometriosis, anxiety, and depression may be connected through a shared genetic basis.

But the experience patients with endometriosis go through also lends itself to the development of mood disorders, said Daniel Ginn, DO, assistant clinical professor of Obstetrics and Gynecology at the David Geffen School of Medicine at the University of California, Los Angeles. Ginn specializes in the treatment of endometriosis and was not a part of the study.

Beyond postpartum depression, Ginn wasn’t surprised by the association of endometriosis with anxiety or OCD because what he hears from patients “on a daily basis is the telling of a history that has been hallmarked by not being listened to, not being believed, and not having symptoms managed well.”

As a result, he said many patients focus heavily on learning about their condition, coming into office visits with binders full of test results and information in an effort to understand and manage it themselves. This “does lead to a certain sense of a need to grasp for control because no one else is helping them [treat their condition effectively].”

He added: “I find it hard to believe that anxiety and OCD were preexisting of the conditions rather than the consequence of a long-term suboptimally managed disease.”

The authors reported no disclosures or sources of funding.

A version of this article first appeared on Medscape.com.

Women with endometriosis have a much higher risk of being diagnosed with several psychiatric disorders during the postpartum period according to an oral abstract presented at the American Society for Reproductive Medicine’s 2024 Scientific Congress and Expo in Denver, Colorado.

Researchers compared rates of postpartum depression, anxiety, mood disturbance (temporary low or anxious mood requiring no treatment), and obsessive-compulsive disorder (OCD) diagnoses among over 200 million adult women from 67 healthcare organizations who had a child between 2005 and 2023.

Within a year after giving birth, women with prepregnancy endometriosis were 25% more likely to be diagnosed with postpartum depression, 85% more likely to be diagnosed with postpartum mood disturbance, 44% more likely to be diagnosed with anxiety, and 1.26 times more likely to be diagnosed with OCD.

About 75% of women studied had no preexisting depression. This population had a 17% higher risk of receiving a postpartum depression diagnosis, a 95% higher risk of receiving an OCD diagnosis, a 72% higher risk of receiving a postpartum mood disturbance diagnosis, and a 38% risk of receiving an anxiety diagnosis.

Among women without preexisting depression, the risk increased by 64% for OCD, 42% for postpartum mood disturbance, and 25% for anxiety, while the risk for postpartum depression was negligible, indicating that women already experiencing depression likely have a higher baseline risk for worsening symptoms postpartum, said the study’s lead author Tina Yi-Jin Hsieh, MD, MPH, biomedical researcher at Harvard Medical School in Boston, Massachusetts.

“We think that because preexisting depression is the more dominant risk factor, it doesn’t really matter if you have another additional risk factor like endometriosis to really change the risk of postpartum depression,” said Hsieh.

Endometriosis is a debilitating condition in which tissue similar to uterine lining grows on the outside of the uterus, causing chronic pain and infertility. It affects between 6% and 10% of women worldwide and takes an average of between 4 and 11 years to be diagnosed. It has been linked to depression and anxiety disorders, yet the study authors say there’s little research examining its impact on women in the year after giving birth.

“Endometriosis is a complex condition that can affect both physical and mental health over much of a person’s life,” said Anna Modest, PhD, assistant professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School and a study author. “Perinatal and maternal mental health can have a huge impact on children and their family — we need to better understand who is at risk for challenges in the postpartum period.”

“Most chronic medical illnesses, particularly those causing pain, have been shown to increase the risk of mood disorders,” said Ripal Shah, MD, MPH, clinical associate professor of Psychiatry and Behavioral Sciences at Stanford Medicine in California. Shah specializes in reproductive psychiatry and was not associated with the study.

“What’s interesting about endometriosis though is that genome-wide association studies have shown that there may be a genetic predisposition for some women to develop both endometriosis and a mood disorder,” said Shah.

A 2023 study suggested that endometriosis, anxiety, and depression may be connected through a shared genetic basis.

But the experience patients with endometriosis go through also lends itself to the development of mood disorders, said Daniel Ginn, DO, assistant clinical professor of Obstetrics and Gynecology at the David Geffen School of Medicine at the University of California, Los Angeles. Ginn specializes in the treatment of endometriosis and was not a part of the study.

Beyond postpartum depression, Ginn wasn’t surprised by the association of endometriosis with anxiety or OCD because what he hears from patients “on a daily basis is the telling of a history that has been hallmarked by not being listened to, not being believed, and not having symptoms managed well.”

As a result, he said many patients focus heavily on learning about their condition, coming into office visits with binders full of test results and information in an effort to understand and manage it themselves. This “does lead to a certain sense of a need to grasp for control because no one else is helping them [treat their condition effectively].”

He added: “I find it hard to believe that anxiety and OCD were preexisting of the conditions rather than the consequence of a long-term suboptimally managed disease.”

The authors reported no disclosures or sources of funding.

A version of this article first appeared on Medscape.com.

TOPLINE: 

Virtual yoga classes significantly reduced chronic low back pain intensity and improved back-related function in health system employees. Improvements were sustained at 24 weeks, with reduced pain medication use and better sleep quality.

METHODOLOGY:

• A single-blinded, 24-week, 2-arm, randomized clinical trial was conducted from May 3, 2022, through May 23, 2023, comparing live-streamed yoga classes with a wait-list control among adults with chronic low back pain.
• A total of 140 participants aged 18-64 years with chronic low back pain were recruited from the Cleveland Clinic Employee Health Plan.
• Inclusion criteria included a mean low back pain intensity score of at least 4 on an 11-point numerical rating scale and daily back pain interference about half or more of the days.
• The intervention consisted of 12 consecutive weekly, 60-minute, virtual, live-streamed hatha yoga group classes.

Coprimary outcomes were mean pain intensity in the previous week on the 11-point numerical rating scale and back-related function as assessed using the 23-point modified Roland Morris Disability Questionnaire at 12 weeks.

TAKEAWAY:

• Participants in the virtual yoga group showed greater reductions in mean pain intensity at 12 weeks (mean change, –1.5 points; P < .001) and 24 weeks (mean change, –2.3 points; P < .001) compared to the wait-list control group.
• Back-related function improved significantly in the virtual yoga group at 12 weeks (mean change, –2.8 points; P < .001) and 24 weeks (mean change, –4.6 points; P < .001), compared with the control group.
• Virtual yoga participants reported 21.2 percentage points less use of any analgesic medication during the past week at 24 weeks, compared with the control group.
• Sleep quality improved more in the virtual yoga group at 12 weeks (mean change, 0.4 points; P = .008) and 24 weeks (mean change, 0.4 points; P = .005), compared with the control group.

IN PRACTICE:

“Given the demonstrated noninferiority of yoga to physical therapy, structured virtual yoga programs and physical therapy are reasonable choices for patients with [chronic low back pain] depending on accessibility, cost, and patient preference. These findings support the call by the National Academy of Medicine for increased evidenced-based pain treatments that can be disseminated via technology-based platforms,” wrote the authors of the study.

SOURCE:

The study was led by Hallie Tankha, PhD, Cleveland Clinic in Ohio. It was published online on November 1, 2024, in JAMA Network Open.

LIMITATIONS: 

The study had a low adherence rate, with only 36.6% of participants attending at least 50% of the yoga classes. There was also a higher rate of missing data in the yoga group compared to the control group. The study did not include a longer-term follow-up assessment beyond 24 weeks.

DISCLOSURES:

This study was supported by grants from Cleveland Clinic Healthcare Delivery and Implementation Science Center. One coauthor disclosed receiving personal fees from the Blue Cross Blue Shield Association. Eric Roseen, DC, PhD, reported receiving grants from the National Institutes of Health National Center for Complementary and Integrative Health. One coauthor disclosed receiving personal fees from UpToDate and grants from NCCIH related to yoga and tai chi for treatment of pain. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE: 

Virtual yoga classes significantly reduced chronic low back pain intensity and improved back-related function in health system employees. Improvements were sustained at 24 weeks, with reduced pain medication use and better sleep quality.

METHODOLOGY:

• A single-blinded, 24-week, 2-arm, randomized clinical trial was conducted from May 3, 2022, through May 23, 2023, comparing live-streamed yoga classes with a wait-list control among adults with chronic low back pain.
• A total of 140 participants aged 18-64 years with chronic low back pain were recruited from the Cleveland Clinic Employee Health Plan.
• Inclusion criteria included a mean low back pain intensity score of at least 4 on an 11-point numerical rating scale and daily back pain interference about half or more of the days.
• The intervention consisted of 12 consecutive weekly, 60-minute, virtual, live-streamed hatha yoga group classes.

Coprimary outcomes were mean pain intensity in the previous week on the 11-point numerical rating scale and back-related function as assessed using the 23-point modified Roland Morris Disability Questionnaire at 12 weeks.

TAKEAWAY:

• Participants in the virtual yoga group showed greater reductions in mean pain intensity at 12 weeks (mean change, –1.5 points; P < .001) and 24 weeks (mean change, –2.3 points; P < .001) compared to the wait-list control group.
• Back-related function improved significantly in the virtual yoga group at 12 weeks (mean change, –2.8 points; P < .001) and 24 weeks (mean change, –4.6 points; P < .001), compared with the control group.
• Virtual yoga participants reported 21.2 percentage points less use of any analgesic medication during the past week at 24 weeks, compared with the control group.
• Sleep quality improved more in the virtual yoga group at 12 weeks (mean change, 0.4 points; P = .008) and 24 weeks (mean change, 0.4 points; P = .005), compared with the control group.

IN PRACTICE:

“Given the demonstrated noninferiority of yoga to physical therapy, structured virtual yoga programs and physical therapy are reasonable choices for patients with [chronic low back pain] depending on accessibility, cost, and patient preference. These findings support the call by the National Academy of Medicine for increased evidenced-based pain treatments that can be disseminated via technology-based platforms,” wrote the authors of the study.

SOURCE:

The study was led by Hallie Tankha, PhD, Cleveland Clinic in Ohio. It was published online on November 1, 2024, in JAMA Network Open.

LIMITATIONS: 

The study had a low adherence rate, with only 36.6% of participants attending at least 50% of the yoga classes. There was also a higher rate of missing data in the yoga group compared to the control group. The study did not include a longer-term follow-up assessment beyond 24 weeks.

DISCLOSURES:

This study was supported by grants from Cleveland Clinic Healthcare Delivery and Implementation Science Center. One coauthor disclosed receiving personal fees from the Blue Cross Blue Shield Association. Eric Roseen, DC, PhD, reported receiving grants from the National Institutes of Health National Center for Complementary and Integrative Health. One coauthor disclosed receiving personal fees from UpToDate and grants from NCCIH related to yoga and tai chi for treatment of pain. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE: 

Virtual yoga classes significantly reduced chronic low back pain intensity and improved back-related function in health system employees. Improvements were sustained at 24 weeks, with reduced pain medication use and better sleep quality.

METHODOLOGY:

• A single-blinded, 24-week, 2-arm, randomized clinical trial was conducted from May 3, 2022, through May 23, 2023, comparing live-streamed yoga classes with a wait-list control among adults with chronic low back pain.
• A total of 140 participants aged 18-64 years with chronic low back pain were recruited from the Cleveland Clinic Employee Health Plan.
• Inclusion criteria included a mean low back pain intensity score of at least 4 on an 11-point numerical rating scale and daily back pain interference about half or more of the days.
• The intervention consisted of 12 consecutive weekly, 60-minute, virtual, live-streamed hatha yoga group classes.

Coprimary outcomes were mean pain intensity in the previous week on the 11-point numerical rating scale and back-related function as assessed using the 23-point modified Roland Morris Disability Questionnaire at 12 weeks.

TAKEAWAY:

• Participants in the virtual yoga group showed greater reductions in mean pain intensity at 12 weeks (mean change, –1.5 points; P < .001) and 24 weeks (mean change, –2.3 points; P < .001) compared to the wait-list control group.
• Back-related function improved significantly in the virtual yoga group at 12 weeks (mean change, –2.8 points; P < .001) and 24 weeks (mean change, –4.6 points; P < .001), compared with the control group.
• Virtual yoga participants reported 21.2 percentage points less use of any analgesic medication during the past week at 24 weeks, compared with the control group.
• Sleep quality improved more in the virtual yoga group at 12 weeks (mean change, 0.4 points; P = .008) and 24 weeks (mean change, 0.4 points; P = .005), compared with the control group.

IN PRACTICE:

“Given the demonstrated noninferiority of yoga to physical therapy, structured virtual yoga programs and physical therapy are reasonable choices for patients with [chronic low back pain] depending on accessibility, cost, and patient preference. These findings support the call by the National Academy of Medicine for increased evidenced-based pain treatments that can be disseminated via technology-based platforms,” wrote the authors of the study.

SOURCE:

The study was led by Hallie Tankha, PhD, Cleveland Clinic in Ohio. It was published online on November 1, 2024, in JAMA Network Open.

LIMITATIONS: 

The study had a low adherence rate, with only 36.6% of participants attending at least 50% of the yoga classes. There was also a higher rate of missing data in the yoga group compared to the control group. The study did not include a longer-term follow-up assessment beyond 24 weeks.

DISCLOSURES:

This study was supported by grants from Cleveland Clinic Healthcare Delivery and Implementation Science Center. One coauthor disclosed receiving personal fees from the Blue Cross Blue Shield Association. Eric Roseen, DC, PhD, reported receiving grants from the National Institutes of Health National Center for Complementary and Integrative Health. One coauthor disclosed receiving personal fees from UpToDate and grants from NCCIH related to yoga and tai chi for treatment of pain. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Many people with rheumatologic diseases try supplements for symptom relief. Here’s what you need to know about some common picks.

Dietary supplements were a $159 billion business in the United States in 2023, and many people with rheumatologic diseases are buying in. Research suggests more than 6 in 10 people with fibromyalgia, nearly 8 in 10 people with Sjögren’s disease, and more than 8 in 10 people with rheumatoid arthritis (RA) take dietary supplements.

Whatever the symptom — pain, swelling, or fatigue — you can probably find a supplement purporting to relieve it. But do these supplements work, and are they safe? A study review in RMD Open comprising 24 systematic reviews and 150 original articles suggests more high-quality research is needed on the effects of dietary supplements on rheumatologic diseases. Most studies have focused on RA or osteoarthritis (OA), where the evidence level is moderate at best.

Dr. Janet Funk

“The studies in this space are usually not very high quality because there’s no money to support them, among other things, plus the products are disparate,” said Janet Funk, MD, MS, professor in the School of Nutritional Sciences and Wellness at the University of Arizona, Tucson. She recommended brushing up on supplements and finding out what patients are taking so you can offer advice and watch for drug-supplement interactions.

When asked for a medication list, many patients forget to report supplements, Funk said. “You have to prompt them specifically. I think some physicians have very negative views about supplements because so little data is known, and patients might pick up on that and decide not to report their use.” She recommended saying something like: “To give you the best possible care, I want to know everything you’re taking, including supplements. The things I’m prescribing could maybe interact with the things you’re taking, so I want to make sure I know about all of it so that together we can figure out if the combination of things is safe.”

The quality of dietary supplements varies, and they aren’t regulated like drugs by the Food and Drug Administration. Funk recommended selecting products verified by NSF or ConsumerLab. They test supplements to ensure the label reflects what’s inside.

This news organization scoured the literature and asked experts to weigh in on the evidence behind popular supplements in rheumatology today.
 

The Essential Nutrients

Vitamin supplements are a staple in many homes — but are they helpful? “Individual vitamin supplements will not provide any benefit unless the person is deficient in a specific vitamin or mineral,” according to Elena Philippou, PhD, RD, associate professor of nutrition-dietetics at the University of Nicosia in Cyprus, and Elena Nikiphorou, MBBS, a rheumatologist at King’s College London in England. For some patients, deficiency is a reality. A retrospective cohort study in The Journal of Clinical Medicine found that people with RA were 17% more likely than age-matched control individuals to have nutrient deficiencies, perhaps because symptoms like fatigue, pain, and nausea affect their eating habits. Here’s what the science says about common vitamin supplements.

Dr. Elena Philippou

Vitamin D. This hormone-like vitamin, which attaches to receptors on immune cells to tamp down inflammation, was the most popular dietary supplement among rheumatology patients in a recent study from the United Kingdom. Vitamin D deficiency is common in people with RA, lupus, Sjögren’s disease, ankylosing spondylitis, systemic sclerosis, and fibromyalgia. In some cases, vitamin D levels track with disease activity, research suggests. Corticosteroids can also make vitamin D deficiency more likely. Can supplements help?

In RA, evidence points to small improvements. A systematic review of 11 studies including 3049 patients published in Nutrition Reviews showed that vitamin D supplements significantly reduced patients’ pain and Disease Activity Score in 28 joints (DAS28) using both C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

The research is mixed on the benefits of vitamin D supplementation for fibromyalgia symptoms, according to a study review in SN Comprehensive Clinical Medicine that included two studies and 80 patients on supplementation. However, researchers said it’s still worth discussing the potential benefits of taking vitamin D.

“Vitamin D supplementation is important in the context of various rheumatic diseases to prevent or treat bone disease,” said Philippou and Nikiphorou. “People with rheumatic disease should speak to their healthcare provider and ask to check their blood vitamin D concentration.” The results can help you recommend a dose.

Folate. Patients on methotrexate should take folic acid supplements under the guidance of a healthcare provider, said Philippou and Nikiphorou. The reason: Methotrexate can deplete folic acid levels, increasing the risk for side effects. An analysis of adverse event reports published showed that methotrexate users who took folic acid (or tumor necrosis factor–alpha inhibitors) had a reduced risk for hepatotoxicity or myelosuppression. A commonly recommended dose is 1 mg/d.

Vitamin B12. In a 2024 perspective paper in Rheumatology International, researchers said physicians should assess vitamin B12 levels early in the diagnostic process of rheumatologic diseases. One reason: Many symptoms of pernicious anemia, like fatigue, mimic symptoms of rheumatologic diseases. The gastrointestinal (GI) effects of systemic sclerosis could bring on vitamin B12 deficiency. In a small study in The Journal of Clinical Rheumatology, 44 of 62 patients with systemic sclerosis had low vitamin B12 levels.

Vitamin E. Vitamin E deficiency is rare in healthy adults. However, some medical conditions, like inflammatory bowel disease and malabsorption disorders, can make vitamin E deficiency more likely. In RA, a vitamin E supplement could help reduce joint swelling and sensitivity, according to a systematic review of nine studies including 39,845 patients in The European Journal of Clinical Nutrition. Researchers credit the nutrient’s role in aiding intestinal repair. Use with caution, as this supplement can increase bleeding risk in doses over 1000 mg/d.

Vitamin A. Like vitamin E, vitamin A deficiency is rare in the United States. The risk of oversupplementing is higher than undersupplementing. However, vitamin A deficiency can happen in people with chronic pancreatic, liver, or GI problems. In people with deficiency, a vitamin A supplement can help relieve dry eye symptoms common in Sjögren’s disease, suggests a narrative review published in Nutrients. Vitamin A might help reduce ocular surface changes by supporting the production of proteins that protect the outermost surfaces of the eyes. The recommended daily allowance for vitamin A is 900 μg. High-dose supplements can cause toxicity, resulting in GI symptoms and problems like lethargy, drowsiness, increased intracranial pressure, and skin changes.
 

The Replacements

These substances are similar to naturally occurring compounds in our bodies. The question is whether ingesting them yields benefits.

Glucosamine and chondroitin. Glucosamine and chondroitin occur naturally in our bodies and help us form and protect connective tissues. In pill form, this combo is the most popular dietary supplement for OA, according to research in the journal Maturitas. But studies of its effectiveness yield mixed results. A systematic review of 25 studies published in Inflammopharmacology showed that, in patients with knee OA, supplementation with about 1500 mg of glucosamine per day reduced tibiofemoral joint space narrowing, while supplementation with about 800 mg/d of chondroitin reduced pain intensity and improved physical function, compared with placebo. The duo of glucosamine and chondroitin did not bring significant benefits, perhaps because more studies are needed. Most side effects were mild, but some literature points to the potential for glucosamine to increase warfarin’s blood-thinning effects.

Omega-3 fatty acids. Fish oil is a top-selling supplement, and it might be helpful in inflammatory rheumatologic diseases. A systematic review of 30 studies including 710 patients published in Arthritis Research & Therapy showed that omega-3 fatty acid supplements can improve pain, swollen and tender joint count, DAS28 scores, and Health Assessment Questionnaire scores in patients with RA, psoriatic arthritis, or ankylosing spondylitis. In patients with lupus, a study review that included five studies and 284 patients in The International Journal of Environmental Research and Public Health suggested omega-3 fatty acid supplements could improve ESR, CRP, disease activity, inflammatory markers, oxidative stress, lipid levels, and endothelial function.

Omega-3 fatty acids have anti-inflammatory effects that might explain their benefits. In patients with RA, for example, fish oil supplementation was associated with elevated blood levels of resolvins and protectins, which help quell inflammation, according to a study in Prostaglandins, Leukotrienes and Essential Fatty Acids.

Philippou and Nikiphorou recommended combining food and supplements: Eat oily fish at least twice a week, regularly consume plant-based sources of omega-3s — like chia seeds, flaxseeds, or walnuts — and consider a daily supplement that contains 2 g of omega-3s from docosahexaenoic acid and eicosapentaenoic acid. Most fish oil side effects are mild, like heartburn and bad breath. Fish oil can have blood-thinning effects at high doses, so special attention is needed for patients on anticoagulants.

Probiotics. Building up the good bacteria in your gut might help you fight the effects of rheumatologic diseases. A systematic review of 80 randomized controlled trials in BMC Medicine suggested that therapies targeting the gut microbiota might improve the symptoms or inflammatory factors in celiac disease, lupus, juvenile idiopathic arthritis, psoriasis, Sjögren’s disease, multiple sclerosis, systemic sclerosis, Crohn’s disease, and ulcerative colitis. Probiotics were also shown to relieve pain in fibromyalgia, but they didn’t affect scores on the Fibromyalgia Impact Questionnaire. Probiotics were not helpful in spondyloarthritis or RA. There were no adverse events. By improving the balance of bacteria in the gut, probiotics might inhibit pro-inflammatory factors and signaling pathways and regulate CD4+ T-cell differentiation, the researchers wrote.

Not all probiotic supplements are created equal. Effects can vary by microorganism and dose. Until more high-quality studies are published, Philippou and Nikiphorou recommend daily consumption of probiotic food sources such as yogurt, kefir, sauerkraut, kimchi, tempeh, miso, and kombucha, along with prebiotic food sources such as bananas, onion, artichokes, asparagus, oats, leeks, and garlic.

Collagen. An increasingly popular supplement for hair, skin, and nails, some collagen peptide or hydrolyzed collagen supplements come with claims about joint health, too. Inside our bodies, collagen helps build joints. As a supplement, the jury is still out. A systematic review of 19 studies in The International Journal of Rheumatic Diseases suggested more research is needed to determine whether collagen supplements are harmful or helpful in OA or RA. Studies haven’t shown adverse events, and doses typically range from 2.5 to 15 g/d.

Coenzyme Q10 (CoQ10). This antioxidant occurs naturally in our cells and is produced through microbial fermentation for use in dietary supplements. A study review of 20 articles including 483 patients in Clinical Nutrition ESPEN concluded that CoQ10 supplementation up to 300 mg/d was beneficial in RA, fibromyalgia, or antiphospholipid syndrome (APS).

In RA, CoQ10 supplementation improved disease activity index, ESR, and cytokine levels and decreased malondialdehyde. CoQ10 might protect against the overproduction of reactive oxygen species that can promote inflammation and joint damage, the researchers said. In fibromyalgia, CoQ10 was linked with improvements in pain, fatigue, sleep, tender points count, mood disorders, and scores on the Fibromyalgia Impact Questionnaire in most of the included studies. CoQ10 might help in fibromyalgia by improving mitochondrial dysfunction. In APS, CoQ10 improved endothelial function and decreased prothrombotic and pro-inflammatory mediators. CoQ10 might change the expression of genes that promote atherosclerosis. A few patients had GI side effects like nausea and diarrhea, but the supplements were generally well tolerated.

Melatonin. Commonly touted as a sleep aid, this hormone has immune and anti-inflammatory activities that could benefit people with rheumatologic diseases. A study review of 13 articles including 533 patients in Clinical Nutrition ESPEN concluded that melatonin can help improve sleep, pain, and mood in fibromyalgia, OA, and osteoporosis but not in RA. Side effects were minimal, but a few people experienced nausea, drowsiness, nightmares, or headaches. Doses of 5-6 mg/d are likely safe for most adults.
 

The Plant-Derived Antioxidants

Many supplements used in rheumatology are antioxidants derived from herbs, spices, or other plants. When plants encounter stressors, like temperature changes or hungry insects, their secondary metabolism revs up and creates compounds with biological properties. Some of these substances influence inflammatory pathways in the human body, said Luís Silva, PhD, a medicinal chemistry researcher at the Polytechnic Institute of Guarda in Portugal. “If it is possible to reduce these kinds of anti-inflammatory processes, it is also possible that we could help people with inflammatory diseases to a good life, or a better life.”

Dr. Luís Silva

Turmeric and curcumin. You might see this supplement labeled as turmeric, a golden spice in curry powder, or curcumin, an antioxidant compound known as a curcuminoid in turmeric. Curcuminoids might reduce inflammation by scavenging free radicals and inhibiting enzymes that make prostaglandins, Silva said.

Turmeric is the most popular herbal supplement for people with RA, according to Funk’s research. A study review of six publications including 539 patients in Frontiers in Immunology showed that curcumin supplements improved RA patients’ ESR, DAS, swollen joint count, and tender joint count. Turmeric could help patients with OA, too. Patients with OA who took 1000 mg/d of curcumin improved their pain and function, according to a systematic review including 12 studies and 1438 participants in the journal Nutrients. In lupus, small studies are promising but inconclusive, suggested a study review in Frontiers in Immunology.

Watch patients taking turmeric and methotrexate closely, Funk said. Both have been associated with liver problems. Some users also experience GI symptoms like diarrhea because turmeric doesn’t absorb well in the GI tract.

Milk thistle (silymarin). This flowering plant is often marketed as a liver-supporting supplement, but research also suggests promise in RA and OA. A systematic review of 12 studies in Current Rheumatology Reviews suggested that silymarin supplements might help relieve pain, reduce inflammation, and protect the cartilage matrix, synovial membrane, and cartilage cells in joints. This supplement might help via immunomodulatory, anti-inflammatory, antioxidant, and anti-apoptotic properties, the researchers said. Doses of 250-750 mg appear to be safe. Side effects such as gastroenteritis, diarrhea, bloating, and headache can occur.

Boswellia serrata. Sourced from the resin of a tree that grows in dry, mountainous regions of Asia and Africa, Boswellia serrata can help relieve joint pain and stiffness and improve joint function in OA, suggested a systematic review of seven trials involving 545 patients in BMC Complementary Medicine and Therapies. Users saw benefits when taking 100-250 mg/d for 4 weeks or more. Compounds in Boswellia serrata may inhibit 5-lipoxygenase, an enzyme involved in producing inflammatory leukotrienes. No adverse events were reported. In some studies, users have reported GI side effects.

Ginger. Ginger is a popular herbal supplement among people with RA, Funk’s research suggested. One small clinical trial involving 70 patients with RA in the journal Gene showed that taking 1500 mg/d of ginger for 12 weeks improved their DAS and boosted their expression of FoxP3 genes, which are linked with the function of regulatory T cells. A meta-analysis including three studies with 330 patients taking ginger published in the journal Nutrients suggested ginger can reduce pain and systemic inflammation in people with OA. Preclinical studies suggested phenolic compounds in this spicy root, such as gingerols, reduce inflammation through multiple mechanisms.

Funk’s research revealed wide variation in the quality of ginger supplements, reinforcing the importance of selecting an independently verified product. Research suggested a safe dose is up to 2-2.5 g/kg body weight.

Resveratrol. Found in red grapes and red wine, this compound is particularly good at blocking COX-2 enzymes, an important step in the inflammatory cascade, Silva said. “Because of their chemical structure, they have great affinity to these enzymes to lead to their inhibition,” he said. A study review of five articles including 481 patients in The European Journal of Rheumatology showed that people with OA, RA, or Takayasu arteritis who took 250-1000 mg/d of resveratrol saw improvements in pain, function, disease activity, joint swelling, and inflammation, with no side effects.

Cinnamon. This warming spice is gaining popularity as a supplement, reported the American Botanical Council. Cinnamon is often marketed as lowering blood sugar and supporting bone health. In a small study of 36 women with RA published in The Journal of the American College of Nutrition, participants who consumed 2 g/d of cinnamon powder had reduced DASs along with reduced pain and tender and swollen joint counts. Cinnamon may reduce pain by inhibiting prostaglandin and blunt inflammation by reducing the release of arachidonic acid from cell membranes, according to a study review in Frontiers in Pharmacology. GI problems and allergic reactions are among the most common side effects.

Funk, Nikiphorou, Philippou, and Silva all had no relevant disclosures.

A version of this article first appeared on Medscape.com.

Many people with rheumatologic diseases try supplements for symptom relief. Here’s what you need to know about some common picks.

Dietary supplements were a $159 billion business in the United States in 2023, and many people with rheumatologic diseases are buying in. Research suggests more than 6 in 10 people with fibromyalgia, nearly 8 in 10 people with Sjögren’s disease, and more than 8 in 10 people with rheumatoid arthritis (RA) take dietary supplements.

Whatever the symptom — pain, swelling, or fatigue — you can probably find a supplement purporting to relieve it. But do these supplements work, and are they safe? A study review in RMD Open comprising 24 systematic reviews and 150 original articles suggests more high-quality research is needed on the effects of dietary supplements on rheumatologic diseases. Most studies have focused on RA or osteoarthritis (OA), where the evidence level is moderate at best.

Dr. Janet Funk

“The studies in this space are usually not very high quality because there’s no money to support them, among other things, plus the products are disparate,” said Janet Funk, MD, MS, professor in the School of Nutritional Sciences and Wellness at the University of Arizona, Tucson. She recommended brushing up on supplements and finding out what patients are taking so you can offer advice and watch for drug-supplement interactions.

When asked for a medication list, many patients forget to report supplements, Funk said. “You have to prompt them specifically. I think some physicians have very negative views about supplements because so little data is known, and patients might pick up on that and decide not to report their use.” She recommended saying something like: “To give you the best possible care, I want to know everything you’re taking, including supplements. The things I’m prescribing could maybe interact with the things you’re taking, so I want to make sure I know about all of it so that together we can figure out if the combination of things is safe.”

The quality of dietary supplements varies, and they aren’t regulated like drugs by the Food and Drug Administration. Funk recommended selecting products verified by NSF or ConsumerLab. They test supplements to ensure the label reflects what’s inside.

This news organization scoured the literature and asked experts to weigh in on the evidence behind popular supplements in rheumatology today.
 

The Essential Nutrients

Vitamin supplements are a staple in many homes — but are they helpful? “Individual vitamin supplements will not provide any benefit unless the person is deficient in a specific vitamin or mineral,” according to Elena Philippou, PhD, RD, associate professor of nutrition-dietetics at the University of Nicosia in Cyprus, and Elena Nikiphorou, MBBS, a rheumatologist at King’s College London in England. For some patients, deficiency is a reality. A retrospective cohort study in The Journal of Clinical Medicine found that people with RA were 17% more likely than age-matched control individuals to have nutrient deficiencies, perhaps because symptoms like fatigue, pain, and nausea affect their eating habits. Here’s what the science says about common vitamin supplements.

Dr. Elena Philippou

Vitamin D. This hormone-like vitamin, which attaches to receptors on immune cells to tamp down inflammation, was the most popular dietary supplement among rheumatology patients in a recent study from the United Kingdom. Vitamin D deficiency is common in people with RA, lupus, Sjögren’s disease, ankylosing spondylitis, systemic sclerosis, and fibromyalgia. In some cases, vitamin D levels track with disease activity, research suggests. Corticosteroids can also make vitamin D deficiency more likely. Can supplements help?

In RA, evidence points to small improvements. A systematic review of 11 studies including 3049 patients published in Nutrition Reviews showed that vitamin D supplements significantly reduced patients’ pain and Disease Activity Score in 28 joints (DAS28) using both C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

The research is mixed on the benefits of vitamin D supplementation for fibromyalgia symptoms, according to a study review in SN Comprehensive Clinical Medicine that included two studies and 80 patients on supplementation. However, researchers said it’s still worth discussing the potential benefits of taking vitamin D.

“Vitamin D supplementation is important in the context of various rheumatic diseases to prevent or treat bone disease,” said Philippou and Nikiphorou. “People with rheumatic disease should speak to their healthcare provider and ask to check their blood vitamin D concentration.” The results can help you recommend a dose.

Folate. Patients on methotrexate should take folic acid supplements under the guidance of a healthcare provider, said Philippou and Nikiphorou. The reason: Methotrexate can deplete folic acid levels, increasing the risk for side effects. An analysis of adverse event reports published showed that methotrexate users who took folic acid (or tumor necrosis factor–alpha inhibitors) had a reduced risk for hepatotoxicity or myelosuppression. A commonly recommended dose is 1 mg/d.

Vitamin B12. In a 2024 perspective paper in Rheumatology International, researchers said physicians should assess vitamin B12 levels early in the diagnostic process of rheumatologic diseases. One reason: Many symptoms of pernicious anemia, like fatigue, mimic symptoms of rheumatologic diseases. The gastrointestinal (GI) effects of systemic sclerosis could bring on vitamin B12 deficiency. In a small study in The Journal of Clinical Rheumatology, 44 of 62 patients with systemic sclerosis had low vitamin B12 levels.

Vitamin E. Vitamin E deficiency is rare in healthy adults. However, some medical conditions, like inflammatory bowel disease and malabsorption disorders, can make vitamin E deficiency more likely. In RA, a vitamin E supplement could help reduce joint swelling and sensitivity, according to a systematic review of nine studies including 39,845 patients in The European Journal of Clinical Nutrition. Researchers credit the nutrient’s role in aiding intestinal repair. Use with caution, as this supplement can increase bleeding risk in doses over 1000 mg/d.

Vitamin A. Like vitamin E, vitamin A deficiency is rare in the United States. The risk of oversupplementing is higher than undersupplementing. However, vitamin A deficiency can happen in people with chronic pancreatic, liver, or GI problems. In people with deficiency, a vitamin A supplement can help relieve dry eye symptoms common in Sjögren’s disease, suggests a narrative review published in Nutrients. Vitamin A might help reduce ocular surface changes by supporting the production of proteins that protect the outermost surfaces of the eyes. The recommended daily allowance for vitamin A is 900 μg. High-dose supplements can cause toxicity, resulting in GI symptoms and problems like lethargy, drowsiness, increased intracranial pressure, and skin changes.
 

The Replacements

These substances are similar to naturally occurring compounds in our bodies. The question is whether ingesting them yields benefits.

Glucosamine and chondroitin. Glucosamine and chondroitin occur naturally in our bodies and help us form and protect connective tissues. In pill form, this combo is the most popular dietary supplement for OA, according to research in the journal Maturitas. But studies of its effectiveness yield mixed results. A systematic review of 25 studies published in Inflammopharmacology showed that, in patients with knee OA, supplementation with about 1500 mg of glucosamine per day reduced tibiofemoral joint space narrowing, while supplementation with about 800 mg/d of chondroitin reduced pain intensity and improved physical function, compared with placebo. The duo of glucosamine and chondroitin did not bring significant benefits, perhaps because more studies are needed. Most side effects were mild, but some literature points to the potential for glucosamine to increase warfarin’s blood-thinning effects.

Omega-3 fatty acids. Fish oil is a top-selling supplement, and it might be helpful in inflammatory rheumatologic diseases. A systematic review of 30 studies including 710 patients published in Arthritis Research & Therapy showed that omega-3 fatty acid supplements can improve pain, swollen and tender joint count, DAS28 scores, and Health Assessment Questionnaire scores in patients with RA, psoriatic arthritis, or ankylosing spondylitis. In patients with lupus, a study review that included five studies and 284 patients in The International Journal of Environmental Research and Public Health suggested omega-3 fatty acid supplements could improve ESR, CRP, disease activity, inflammatory markers, oxidative stress, lipid levels, and endothelial function.

Omega-3 fatty acids have anti-inflammatory effects that might explain their benefits. In patients with RA, for example, fish oil supplementation was associated with elevated blood levels of resolvins and protectins, which help quell inflammation, according to a study in Prostaglandins, Leukotrienes and Essential Fatty Acids.

Philippou and Nikiphorou recommended combining food and supplements: Eat oily fish at least twice a week, regularly consume plant-based sources of omega-3s — like chia seeds, flaxseeds, or walnuts — and consider a daily supplement that contains 2 g of omega-3s from docosahexaenoic acid and eicosapentaenoic acid. Most fish oil side effects are mild, like heartburn and bad breath. Fish oil can have blood-thinning effects at high doses, so special attention is needed for patients on anticoagulants.

Probiotics. Building up the good bacteria in your gut might help you fight the effects of rheumatologic diseases. A systematic review of 80 randomized controlled trials in BMC Medicine suggested that therapies targeting the gut microbiota might improve the symptoms or inflammatory factors in celiac disease, lupus, juvenile idiopathic arthritis, psoriasis, Sjögren’s disease, multiple sclerosis, systemic sclerosis, Crohn’s disease, and ulcerative colitis. Probiotics were also shown to relieve pain in fibromyalgia, but they didn’t affect scores on the Fibromyalgia Impact Questionnaire. Probiotics were not helpful in spondyloarthritis or RA. There were no adverse events. By improving the balance of bacteria in the gut, probiotics might inhibit pro-inflammatory factors and signaling pathways and regulate CD4+ T-cell differentiation, the researchers wrote.

Not all probiotic supplements are created equal. Effects can vary by microorganism and dose. Until more high-quality studies are published, Philippou and Nikiphorou recommend daily consumption of probiotic food sources such as yogurt, kefir, sauerkraut, kimchi, tempeh, miso, and kombucha, along with prebiotic food sources such as bananas, onion, artichokes, asparagus, oats, leeks, and garlic.

Collagen. An increasingly popular supplement for hair, skin, and nails, some collagen peptide or hydrolyzed collagen supplements come with claims about joint health, too. Inside our bodies, collagen helps build joints. As a supplement, the jury is still out. A systematic review of 19 studies in The International Journal of Rheumatic Diseases suggested more research is needed to determine whether collagen supplements are harmful or helpful in OA or RA. Studies haven’t shown adverse events, and doses typically range from 2.5 to 15 g/d.

Coenzyme Q10 (CoQ10). This antioxidant occurs naturally in our cells and is produced through microbial fermentation for use in dietary supplements. A study review of 20 articles including 483 patients in Clinical Nutrition ESPEN concluded that CoQ10 supplementation up to 300 mg/d was beneficial in RA, fibromyalgia, or antiphospholipid syndrome (APS).

In RA, CoQ10 supplementation improved disease activity index, ESR, and cytokine levels and decreased malondialdehyde. CoQ10 might protect against the overproduction of reactive oxygen species that can promote inflammation and joint damage, the researchers said. In fibromyalgia, CoQ10 was linked with improvements in pain, fatigue, sleep, tender points count, mood disorders, and scores on the Fibromyalgia Impact Questionnaire in most of the included studies. CoQ10 might help in fibromyalgia by improving mitochondrial dysfunction. In APS, CoQ10 improved endothelial function and decreased prothrombotic and pro-inflammatory mediators. CoQ10 might change the expression of genes that promote atherosclerosis. A few patients had GI side effects like nausea and diarrhea, but the supplements were generally well tolerated.

Melatonin. Commonly touted as a sleep aid, this hormone has immune and anti-inflammatory activities that could benefit people with rheumatologic diseases. A study review of 13 articles including 533 patients in Clinical Nutrition ESPEN concluded that melatonin can help improve sleep, pain, and mood in fibromyalgia, OA, and osteoporosis but not in RA. Side effects were minimal, but a few people experienced nausea, drowsiness, nightmares, or headaches. Doses of 5-6 mg/d are likely safe for most adults.
 

The Plant-Derived Antioxidants

Many supplements used in rheumatology are antioxidants derived from herbs, spices, or other plants. When plants encounter stressors, like temperature changes or hungry insects, their secondary metabolism revs up and creates compounds with biological properties. Some of these substances influence inflammatory pathways in the human body, said Luís Silva, PhD, a medicinal chemistry researcher at the Polytechnic Institute of Guarda in Portugal. “If it is possible to reduce these kinds of anti-inflammatory processes, it is also possible that we could help people with inflammatory diseases to a good life, or a better life.”

Dr. Luís Silva

Turmeric and curcumin. You might see this supplement labeled as turmeric, a golden spice in curry powder, or curcumin, an antioxidant compound known as a curcuminoid in turmeric. Curcuminoids might reduce inflammation by scavenging free radicals and inhibiting enzymes that make prostaglandins, Silva said.

Turmeric is the most popular herbal supplement for people with RA, according to Funk’s research. A study review of six publications including 539 patients in Frontiers in Immunology showed that curcumin supplements improved RA patients’ ESR, DAS, swollen joint count, and tender joint count. Turmeric could help patients with OA, too. Patients with OA who took 1000 mg/d of curcumin improved their pain and function, according to a systematic review including 12 studies and 1438 participants in the journal Nutrients. In lupus, small studies are promising but inconclusive, suggested a study review in Frontiers in Immunology.

Watch patients taking turmeric and methotrexate closely, Funk said. Both have been associated with liver problems. Some users also experience GI symptoms like diarrhea because turmeric doesn’t absorb well in the GI tract.

Milk thistle (silymarin). This flowering plant is often marketed as a liver-supporting supplement, but research also suggests promise in RA and OA. A systematic review of 12 studies in Current Rheumatology Reviews suggested that silymarin supplements might help relieve pain, reduce inflammation, and protect the cartilage matrix, synovial membrane, and cartilage cells in joints. This supplement might help via immunomodulatory, anti-inflammatory, antioxidant, and anti-apoptotic properties, the researchers said. Doses of 250-750 mg appear to be safe. Side effects such as gastroenteritis, diarrhea, bloating, and headache can occur.

Boswellia serrata. Sourced from the resin of a tree that grows in dry, mountainous regions of Asia and Africa, Boswellia serrata can help relieve joint pain and stiffness and improve joint function in OA, suggested a systematic review of seven trials involving 545 patients in BMC Complementary Medicine and Therapies. Users saw benefits when taking 100-250 mg/d for 4 weeks or more. Compounds in Boswellia serrata may inhibit 5-lipoxygenase, an enzyme involved in producing inflammatory leukotrienes. No adverse events were reported. In some studies, users have reported GI side effects.

Ginger. Ginger is a popular herbal supplement among people with RA, Funk’s research suggested. One small clinical trial involving 70 patients with RA in the journal Gene showed that taking 1500 mg/d of ginger for 12 weeks improved their DAS and boosted their expression of FoxP3 genes, which are linked with the function of regulatory T cells. A meta-analysis including three studies with 330 patients taking ginger published in the journal Nutrients suggested ginger can reduce pain and systemic inflammation in people with OA. Preclinical studies suggested phenolic compounds in this spicy root, such as gingerols, reduce inflammation through multiple mechanisms.

Funk’s research revealed wide variation in the quality of ginger supplements, reinforcing the importance of selecting an independently verified product. Research suggested a safe dose is up to 2-2.5 g/kg body weight.

Resveratrol. Found in red grapes and red wine, this compound is particularly good at blocking COX-2 enzymes, an important step in the inflammatory cascade, Silva said. “Because of their chemical structure, they have great affinity to these enzymes to lead to their inhibition,” he said. A study review of five articles including 481 patients in The European Journal of Rheumatology showed that people with OA, RA, or Takayasu arteritis who took 250-1000 mg/d of resveratrol saw improvements in pain, function, disease activity, joint swelling, and inflammation, with no side effects.

Cinnamon. This warming spice is gaining popularity as a supplement, reported the American Botanical Council. Cinnamon is often marketed as lowering blood sugar and supporting bone health. In a small study of 36 women with RA published in The Journal of the American College of Nutrition, participants who consumed 2 g/d of cinnamon powder had reduced DASs along with reduced pain and tender and swollen joint counts. Cinnamon may reduce pain by inhibiting prostaglandin and blunt inflammation by reducing the release of arachidonic acid from cell membranes, according to a study review in Frontiers in Pharmacology. GI problems and allergic reactions are among the most common side effects.

Funk, Nikiphorou, Philippou, and Silva all had no relevant disclosures.

A version of this article first appeared on Medscape.com.

Many people with rheumatologic diseases try supplements for symptom relief. Here’s what you need to know about some common picks.

Dietary supplements were a $159 billion business in the United States in 2023, and many people with rheumatologic diseases are buying in. Research suggests more than 6 in 10 people with fibromyalgia, nearly 8 in 10 people with Sjögren’s disease, and more than 8 in 10 people with rheumatoid arthritis (RA) take dietary supplements.

Whatever the symptom — pain, swelling, or fatigue — you can probably find a supplement purporting to relieve it. But do these supplements work, and are they safe? A study review in RMD Open comprising 24 systematic reviews and 150 original articles suggests more high-quality research is needed on the effects of dietary supplements on rheumatologic diseases. Most studies have focused on RA or osteoarthritis (OA), where the evidence level is moderate at best.

Dr. Janet Funk

“The studies in this space are usually not very high quality because there’s no money to support them, among other things, plus the products are disparate,” said Janet Funk, MD, MS, professor in the School of Nutritional Sciences and Wellness at the University of Arizona, Tucson. She recommended brushing up on supplements and finding out what patients are taking so you can offer advice and watch for drug-supplement interactions.

When asked for a medication list, many patients forget to report supplements, Funk said. “You have to prompt them specifically. I think some physicians have very negative views about supplements because so little data is known, and patients might pick up on that and decide not to report their use.” She recommended saying something like: “To give you the best possible care, I want to know everything you’re taking, including supplements. The things I’m prescribing could maybe interact with the things you’re taking, so I want to make sure I know about all of it so that together we can figure out if the combination of things is safe.”

The quality of dietary supplements varies, and they aren’t regulated like drugs by the Food and Drug Administration. Funk recommended selecting products verified by NSF or ConsumerLab. They test supplements to ensure the label reflects what’s inside.

This news organization scoured the literature and asked experts to weigh in on the evidence behind popular supplements in rheumatology today.
 

The Essential Nutrients

Vitamin supplements are a staple in many homes — but are they helpful? “Individual vitamin supplements will not provide any benefit unless the person is deficient in a specific vitamin or mineral,” according to Elena Philippou, PhD, RD, associate professor of nutrition-dietetics at the University of Nicosia in Cyprus, and Elena Nikiphorou, MBBS, a rheumatologist at King’s College London in England. For some patients, deficiency is a reality. A retrospective cohort study in The Journal of Clinical Medicine found that people with RA were 17% more likely than age-matched control individuals to have nutrient deficiencies, perhaps because symptoms like fatigue, pain, and nausea affect their eating habits. Here’s what the science says about common vitamin supplements.

Dr. Elena Philippou

Vitamin D. This hormone-like vitamin, which attaches to receptors on immune cells to tamp down inflammation, was the most popular dietary supplement among rheumatology patients in a recent study from the United Kingdom. Vitamin D deficiency is common in people with RA, lupus, Sjögren’s disease, ankylosing spondylitis, systemic sclerosis, and fibromyalgia. In some cases, vitamin D levels track with disease activity, research suggests. Corticosteroids can also make vitamin D deficiency more likely. Can supplements help?

In RA, evidence points to small improvements. A systematic review of 11 studies including 3049 patients published in Nutrition Reviews showed that vitamin D supplements significantly reduced patients’ pain and Disease Activity Score in 28 joints (DAS28) using both C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

The research is mixed on the benefits of vitamin D supplementation for fibromyalgia symptoms, according to a study review in SN Comprehensive Clinical Medicine that included two studies and 80 patients on supplementation. However, researchers said it’s still worth discussing the potential benefits of taking vitamin D.

“Vitamin D supplementation is important in the context of various rheumatic diseases to prevent or treat bone disease,” said Philippou and Nikiphorou. “People with rheumatic disease should speak to their healthcare provider and ask to check their blood vitamin D concentration.” The results can help you recommend a dose.

Folate. Patients on methotrexate should take folic acid supplements under the guidance of a healthcare provider, said Philippou and Nikiphorou. The reason: Methotrexate can deplete folic acid levels, increasing the risk for side effects. An analysis of adverse event reports published showed that methotrexate users who took folic acid (or tumor necrosis factor–alpha inhibitors) had a reduced risk for hepatotoxicity or myelosuppression. A commonly recommended dose is 1 mg/d.

Vitamin B12. In a 2024 perspective paper in Rheumatology International, researchers said physicians should assess vitamin B12 levels early in the diagnostic process of rheumatologic diseases. One reason: Many symptoms of pernicious anemia, like fatigue, mimic symptoms of rheumatologic diseases. The gastrointestinal (GI) effects of systemic sclerosis could bring on vitamin B12 deficiency. In a small study in The Journal of Clinical Rheumatology, 44 of 62 patients with systemic sclerosis had low vitamin B12 levels.

Vitamin E. Vitamin E deficiency is rare in healthy adults. However, some medical conditions, like inflammatory bowel disease and malabsorption disorders, can make vitamin E deficiency more likely. In RA, a vitamin E supplement could help reduce joint swelling and sensitivity, according to a systematic review of nine studies including 39,845 patients in The European Journal of Clinical Nutrition. Researchers credit the nutrient’s role in aiding intestinal repair. Use with caution, as this supplement can increase bleeding risk in doses over 1000 mg/d.

Vitamin A. Like vitamin E, vitamin A deficiency is rare in the United States. The risk of oversupplementing is higher than undersupplementing. However, vitamin A deficiency can happen in people with chronic pancreatic, liver, or GI problems. In people with deficiency, a vitamin A supplement can help relieve dry eye symptoms common in Sjögren’s disease, suggests a narrative review published in Nutrients. Vitamin A might help reduce ocular surface changes by supporting the production of proteins that protect the outermost surfaces of the eyes. The recommended daily allowance for vitamin A is 900 μg. High-dose supplements can cause toxicity, resulting in GI symptoms and problems like lethargy, drowsiness, increased intracranial pressure, and skin changes.
 

The Replacements

These substances are similar to naturally occurring compounds in our bodies. The question is whether ingesting them yields benefits.

Glucosamine and chondroitin. Glucosamine and chondroitin occur naturally in our bodies and help us form and protect connective tissues. In pill form, this combo is the most popular dietary supplement for OA, according to research in the journal Maturitas. But studies of its effectiveness yield mixed results. A systematic review of 25 studies published in Inflammopharmacology showed that, in patients with knee OA, supplementation with about 1500 mg of glucosamine per day reduced tibiofemoral joint space narrowing, while supplementation with about 800 mg/d of chondroitin reduced pain intensity and improved physical function, compared with placebo. The duo of glucosamine and chondroitin did not bring significant benefits, perhaps because more studies are needed. Most side effects were mild, but some literature points to the potential for glucosamine to increase warfarin’s blood-thinning effects.

Omega-3 fatty acids. Fish oil is a top-selling supplement, and it might be helpful in inflammatory rheumatologic diseases. A systematic review of 30 studies including 710 patients published in Arthritis Research & Therapy showed that omega-3 fatty acid supplements can improve pain, swollen and tender joint count, DAS28 scores, and Health Assessment Questionnaire scores in patients with RA, psoriatic arthritis, or ankylosing spondylitis. In patients with lupus, a study review that included five studies and 284 patients in The International Journal of Environmental Research and Public Health suggested omega-3 fatty acid supplements could improve ESR, CRP, disease activity, inflammatory markers, oxidative stress, lipid levels, and endothelial function.

Omega-3 fatty acids have anti-inflammatory effects that might explain their benefits. In patients with RA, for example, fish oil supplementation was associated with elevated blood levels of resolvins and protectins, which help quell inflammation, according to a study in Prostaglandins, Leukotrienes and Essential Fatty Acids.

Philippou and Nikiphorou recommended combining food and supplements: Eat oily fish at least twice a week, regularly consume plant-based sources of omega-3s — like chia seeds, flaxseeds, or walnuts — and consider a daily supplement that contains 2 g of omega-3s from docosahexaenoic acid and eicosapentaenoic acid. Most fish oil side effects are mild, like heartburn and bad breath. Fish oil can have blood-thinning effects at high doses, so special attention is needed for patients on anticoagulants.

Probiotics. Building up the good bacteria in your gut might help you fight the effects of rheumatologic diseases. A systematic review of 80 randomized controlled trials in BMC Medicine suggested that therapies targeting the gut microbiota might improve the symptoms or inflammatory factors in celiac disease, lupus, juvenile idiopathic arthritis, psoriasis, Sjögren’s disease, multiple sclerosis, systemic sclerosis, Crohn’s disease, and ulcerative colitis. Probiotics were also shown to relieve pain in fibromyalgia, but they didn’t affect scores on the Fibromyalgia Impact Questionnaire. Probiotics were not helpful in spondyloarthritis or RA. There were no adverse events. By improving the balance of bacteria in the gut, probiotics might inhibit pro-inflammatory factors and signaling pathways and regulate CD4+ T-cell differentiation, the researchers wrote.

Not all probiotic supplements are created equal. Effects can vary by microorganism and dose. Until more high-quality studies are published, Philippou and Nikiphorou recommend daily consumption of probiotic food sources such as yogurt, kefir, sauerkraut, kimchi, tempeh, miso, and kombucha, along with prebiotic food sources such as bananas, onion, artichokes, asparagus, oats, leeks, and garlic.

Collagen. An increasingly popular supplement for hair, skin, and nails, some collagen peptide or hydrolyzed collagen supplements come with claims about joint health, too. Inside our bodies, collagen helps build joints. As a supplement, the jury is still out. A systematic review of 19 studies in The International Journal of Rheumatic Diseases suggested more research is needed to determine whether collagen supplements are harmful or helpful in OA or RA. Studies haven’t shown adverse events, and doses typically range from 2.5 to 15 g/d.

Coenzyme Q10 (CoQ10). This antioxidant occurs naturally in our cells and is produced through microbial fermentation for use in dietary supplements. A study review of 20 articles including 483 patients in Clinical Nutrition ESPEN concluded that CoQ10 supplementation up to 300 mg/d was beneficial in RA, fibromyalgia, or antiphospholipid syndrome (APS).

In RA, CoQ10 supplementation improved disease activity index, ESR, and cytokine levels and decreased malondialdehyde. CoQ10 might protect against the overproduction of reactive oxygen species that can promote inflammation and joint damage, the researchers said. In fibromyalgia, CoQ10 was linked with improvements in pain, fatigue, sleep, tender points count, mood disorders, and scores on the Fibromyalgia Impact Questionnaire in most of the included studies. CoQ10 might help in fibromyalgia by improving mitochondrial dysfunction. In APS, CoQ10 improved endothelial function and decreased prothrombotic and pro-inflammatory mediators. CoQ10 might change the expression of genes that promote atherosclerosis. A few patients had GI side effects like nausea and diarrhea, but the supplements were generally well tolerated.

Melatonin. Commonly touted as a sleep aid, this hormone has immune and anti-inflammatory activities that could benefit people with rheumatologic diseases. A study review of 13 articles including 533 patients in Clinical Nutrition ESPEN concluded that melatonin can help improve sleep, pain, and mood in fibromyalgia, OA, and osteoporosis but not in RA. Side effects were minimal, but a few people experienced nausea, drowsiness, nightmares, or headaches. Doses of 5-6 mg/d are likely safe for most adults.
 

The Plant-Derived Antioxidants

Many supplements used in rheumatology are antioxidants derived from herbs, spices, or other plants. When plants encounter stressors, like temperature changes or hungry insects, their secondary metabolism revs up and creates compounds with biological properties. Some of these substances influence inflammatory pathways in the human body, said Luís Silva, PhD, a medicinal chemistry researcher at the Polytechnic Institute of Guarda in Portugal. “If it is possible to reduce these kinds of anti-inflammatory processes, it is also possible that we could help people with inflammatory diseases to a good life, or a better life.”

Dr. Luís Silva

Turmeric and curcumin. You might see this supplement labeled as turmeric, a golden spice in curry powder, or curcumin, an antioxidant compound known as a curcuminoid in turmeric. Curcuminoids might reduce inflammation by scavenging free radicals and inhibiting enzymes that make prostaglandins, Silva said.

Turmeric is the most popular herbal supplement for people with RA, according to Funk’s research. A study review of six publications including 539 patients in Frontiers in Immunology showed that curcumin supplements improved RA patients’ ESR, DAS, swollen joint count, and tender joint count. Turmeric could help patients with OA, too. Patients with OA who took 1000 mg/d of curcumin improved their pain and function, according to a systematic review including 12 studies and 1438 participants in the journal Nutrients. In lupus, small studies are promising but inconclusive, suggested a study review in Frontiers in Immunology.

Watch patients taking turmeric and methotrexate closely, Funk said. Both have been associated with liver problems. Some users also experience GI symptoms like diarrhea because turmeric doesn’t absorb well in the GI tract.

Milk thistle (silymarin). This flowering plant is often marketed as a liver-supporting supplement, but research also suggests promise in RA and OA. A systematic review of 12 studies in Current Rheumatology Reviews suggested that silymarin supplements might help relieve pain, reduce inflammation, and protect the cartilage matrix, synovial membrane, and cartilage cells in joints. This supplement might help via immunomodulatory, anti-inflammatory, antioxidant, and anti-apoptotic properties, the researchers said. Doses of 250-750 mg appear to be safe. Side effects such as gastroenteritis, diarrhea, bloating, and headache can occur.

Boswellia serrata. Sourced from the resin of a tree that grows in dry, mountainous regions of Asia and Africa, Boswellia serrata can help relieve joint pain and stiffness and improve joint function in OA, suggested a systematic review of seven trials involving 545 patients in BMC Complementary Medicine and Therapies. Users saw benefits when taking 100-250 mg/d for 4 weeks or more. Compounds in Boswellia serrata may inhibit 5-lipoxygenase, an enzyme involved in producing inflammatory leukotrienes. No adverse events were reported. In some studies, users have reported GI side effects.

Ginger. Ginger is a popular herbal supplement among people with RA, Funk’s research suggested. One small clinical trial involving 70 patients with RA in the journal Gene showed that taking 1500 mg/d of ginger for 12 weeks improved their DAS and boosted their expression of FoxP3 genes, which are linked with the function of regulatory T cells. A meta-analysis including three studies with 330 patients taking ginger published in the journal Nutrients suggested ginger can reduce pain and systemic inflammation in people with OA. Preclinical studies suggested phenolic compounds in this spicy root, such as gingerols, reduce inflammation through multiple mechanisms.

Funk’s research revealed wide variation in the quality of ginger supplements, reinforcing the importance of selecting an independently verified product. Research suggested a safe dose is up to 2-2.5 g/kg body weight.

Resveratrol. Found in red grapes and red wine, this compound is particularly good at blocking COX-2 enzymes, an important step in the inflammatory cascade, Silva said. “Because of their chemical structure, they have great affinity to these enzymes to lead to their inhibition,” he said. A study review of five articles including 481 patients in The European Journal of Rheumatology showed that people with OA, RA, or Takayasu arteritis who took 250-1000 mg/d of resveratrol saw improvements in pain, function, disease activity, joint swelling, and inflammation, with no side effects.

Cinnamon. This warming spice is gaining popularity as a supplement, reported the American Botanical Council. Cinnamon is often marketed as lowering blood sugar and supporting bone health. In a small study of 36 women with RA published in The Journal of the American College of Nutrition, participants who consumed 2 g/d of cinnamon powder had reduced DASs along with reduced pain and tender and swollen joint counts. Cinnamon may reduce pain by inhibiting prostaglandin and blunt inflammation by reducing the release of arachidonic acid from cell membranes, according to a study review in Frontiers in Pharmacology. GI problems and allergic reactions are among the most common side effects.

Funk, Nikiphorou, Philippou, and Silva all had no relevant disclosures.

A version of this article first appeared on Medscape.com.

Methadone has been shown to be highly effective for opioid use disorder. So why is it still so difficult to prescribe in the United States and is that about to change?

A recent study from Canada adds to the growing body of evidence supporting methadone’s effectiveness in treating opioid use disorder and bolsters efforts to expand access in the United States by removing restrictive barriers.

This paper included more than 30,000 patients with opioid use disorder and showed those on methadone were almost 60% significantly less likely to stop treatment at 24 months than their peers assigned to buprenorphine/naloxone (adjusted hazard ratio [aHR], 1.58), with no difference in mortality risk (aHR, 0.57).

“In Canada, unlike the US, methadone and buprenorphine/naloxone are both available in office-based settings. Methadone really outperforms buprenorphine/naloxone in being able to retain people in treatment, which is our main goal and comes with a host of benefits,” Bohdan Nosyk, PhD, with Simon Fraser University in Burnaby, British Columbia, Canada, who worked on the study, said in an interview.

In addition, a recent systematic review and meta-analysis of relevant research involving more than 1 million patients with opioid use disorder also showed better treatment retention with methadone than with buprenorphine.

During the COVID-19 pandemic, relaxed methadone regulations, that included take-home medications, did not lead to an increase in overdoses. Instead, these changes improved treatment retention and patient experiences, highlighting the potential benefits of further deregulation.
 

‘Atrocious’ Outdated Policies

However, despite methadone’s proven efficacy and safety for opioid use disorder, it remains vastly underutilized because of outdated US policies restricting its use to opioid treatment programs (OTPs).

“It’s absolutely atrocious that methadone policies have not kept up with the evidence. If you look at other countries that have expanded their access to methadone, their overdose rates have fallen dramatically,” said Leslie Suen, MD, with the University of California, San Francisco, and coauthor of a recent JAMA Viewpoint on this topic.

“Methadone is a very good medication that’s been shown over and over to be very effective and safe,” Alan Leshner, PhD, past director of the National Institute on Drug Abuse, said in an interview.

“There is no reason why it couldn’t be administered through pharmacies or through physicians’ offices as long as it’s done in a controlled and careful way,” said Leshner.

Leshner chaired the committee that produced the 2019 report Medications for Opioid Use Disorder Save Lives.

“We learned during COVID that increasing the amount of take-home methadone and increasing access does not lead to an increase in deaths or an increase in overdose, so it’s hard to find a reason not to do it,” he said.
 

Change Finally on the Horizon?

Several recent and proposed policy changes could revolutionize methadone delivery in the United States.

In March 2022, in response to the pandemic, the Drug Enforcement Administration (DEA) allowed hospitals to dispense up to a 3-day supply of methadone (known as the 72-hour rule) to bridge care transitions without needing OTPs.

In April 2024, the Substance Abuse and Mental Health Services Administration and DEA codified many methadone and buprenorphine delivery flexibilities granted temporarily during the pandemic, including increased use of telehealth assessments and earlier access to take-home methadone doses.

Another contemporary policy change is expansion of the Americans with Disabilities Act mandating that patients taking medications for opioid use disorder, such as methadone, be able to continue treatment when transitioning to settings such as hospitals, jails, and skilled nursing facilities.

At the state level, California Governor Gavin Newsom recently signed a bill, effective immediately, that expands access to methadone treatment in his state.

On the horizon at the federal level is the Modernizing Opioid Treatment Access Act (MOTAA) — the bipartisan and bicameral bill introduced by Sen. Ed Markey (D-MA) and Sen. Rand Paul (R-KY), along with Rep. Donald Norcross (D-NJ) and Rep. Don Bacon, (R-NE) — that would allow methadone to be prescribed by addiction specialists and dispensed in community pharmacies.
 

An Ethical Imperative

“With only about 2000 OTP clinics clustered in urban areas, less than 25% of people who are diagnosed with opioid use disorder are actually able to access methadone,” Caty Simon, with the National Survivors Union, Greensboro, North Carolina, and coauthor of the JAMA Viewpoint, said in an interview.

While MOTAA represents a major step forward, limiting methadone prescribing to addiction specialists may not fully address the treatment gap, particularly in rural and underserved areas, Simon said.

To optimize methadone’s potential, she’d like to see further expansion of prescribing privileges to general healthcare providers.

“As someone with lived and living experience of opioid use and treatment, and somebody who works nationally and locally in organizations of people impacted by drug use, I know people in my area right now — marginalized people of color — who would have much better chances of survival if they were able to access methadone. If MOTAA passed tomorrow, we could save so many lives. There is an ethical imperative to pass it,” Simon said.

Leshner said he is “always very concerned about access, particularly for underserved populations, poor people, people living in rural areas. If you can access the medications you need, you’re in big trouble.”

Is this methadone’s moment? “I’m a little optimistic, but I haven’t seen the progress I would like to see,” Leshner said.

A version of this article first appeared on Medscape.com.

Methadone has been shown to be highly effective for opioid use disorder. So why is it still so difficult to prescribe in the United States and is that about to change?

A recent study from Canada adds to the growing body of evidence supporting methadone’s effectiveness in treating opioid use disorder and bolsters efforts to expand access in the United States by removing restrictive barriers.

This paper included more than 30,000 patients with opioid use disorder and showed those on methadone were almost 60% significantly less likely to stop treatment at 24 months than their peers assigned to buprenorphine/naloxone (adjusted hazard ratio [aHR], 1.58), with no difference in mortality risk (aHR, 0.57).

“In Canada, unlike the US, methadone and buprenorphine/naloxone are both available in office-based settings. Methadone really outperforms buprenorphine/naloxone in being able to retain people in treatment, which is our main goal and comes with a host of benefits,” Bohdan Nosyk, PhD, with Simon Fraser University in Burnaby, British Columbia, Canada, who worked on the study, said in an interview.

In addition, a recent systematic review and meta-analysis of relevant research involving more than 1 million patients with opioid use disorder also showed better treatment retention with methadone than with buprenorphine.

During the COVID-19 pandemic, relaxed methadone regulations, that included take-home medications, did not lead to an increase in overdoses. Instead, these changes improved treatment retention and patient experiences, highlighting the potential benefits of further deregulation.
 

‘Atrocious’ Outdated Policies

However, despite methadone’s proven efficacy and safety for opioid use disorder, it remains vastly underutilized because of outdated US policies restricting its use to opioid treatment programs (OTPs).

“It’s absolutely atrocious that methadone policies have not kept up with the evidence. If you look at other countries that have expanded their access to methadone, their overdose rates have fallen dramatically,” said Leslie Suen, MD, with the University of California, San Francisco, and coauthor of a recent JAMA Viewpoint on this topic.

“Methadone is a very good medication that’s been shown over and over to be very effective and safe,” Alan Leshner, PhD, past director of the National Institute on Drug Abuse, said in an interview.

“There is no reason why it couldn’t be administered through pharmacies or through physicians’ offices as long as it’s done in a controlled and careful way,” said Leshner.

Leshner chaired the committee that produced the 2019 report Medications for Opioid Use Disorder Save Lives.

“We learned during COVID that increasing the amount of take-home methadone and increasing access does not lead to an increase in deaths or an increase in overdose, so it’s hard to find a reason not to do it,” he said.
 

Change Finally on the Horizon?

Several recent and proposed policy changes could revolutionize methadone delivery in the United States.

In March 2022, in response to the pandemic, the Drug Enforcement Administration (DEA) allowed hospitals to dispense up to a 3-day supply of methadone (known as the 72-hour rule) to bridge care transitions without needing OTPs.

In April 2024, the Substance Abuse and Mental Health Services Administration and DEA codified many methadone and buprenorphine delivery flexibilities granted temporarily during the pandemic, including increased use of telehealth assessments and earlier access to take-home methadone doses.

Another contemporary policy change is expansion of the Americans with Disabilities Act mandating that patients taking medications for opioid use disorder, such as methadone, be able to continue treatment when transitioning to settings such as hospitals, jails, and skilled nursing facilities.

At the state level, California Governor Gavin Newsom recently signed a bill, effective immediately, that expands access to methadone treatment in his state.

On the horizon at the federal level is the Modernizing Opioid Treatment Access Act (MOTAA) — the bipartisan and bicameral bill introduced by Sen. Ed Markey (D-MA) and Sen. Rand Paul (R-KY), along with Rep. Donald Norcross (D-NJ) and Rep. Don Bacon, (R-NE) — that would allow methadone to be prescribed by addiction specialists and dispensed in community pharmacies.
 

An Ethical Imperative

“With only about 2000 OTP clinics clustered in urban areas, less than 25% of people who are diagnosed with opioid use disorder are actually able to access methadone,” Caty Simon, with the National Survivors Union, Greensboro, North Carolina, and coauthor of the JAMA Viewpoint, said in an interview.

While MOTAA represents a major step forward, limiting methadone prescribing to addiction specialists may not fully address the treatment gap, particularly in rural and underserved areas, Simon said.

To optimize methadone’s potential, she’d like to see further expansion of prescribing privileges to general healthcare providers.

“As someone with lived and living experience of opioid use and treatment, and somebody who works nationally and locally in organizations of people impacted by drug use, I know people in my area right now — marginalized people of color — who would have much better chances of survival if they were able to access methadone. If MOTAA passed tomorrow, we could save so many lives. There is an ethical imperative to pass it,” Simon said.

Leshner said he is “always very concerned about access, particularly for underserved populations, poor people, people living in rural areas. If you can access the medications you need, you’re in big trouble.”

Is this methadone’s moment? “I’m a little optimistic, but I haven’t seen the progress I would like to see,” Leshner said.

A version of this article first appeared on Medscape.com.

Methadone has been shown to be highly effective for opioid use disorder. So why is it still so difficult to prescribe in the United States and is that about to change?

A recent study from Canada adds to the growing body of evidence supporting methadone’s effectiveness in treating opioid use disorder and bolsters efforts to expand access in the United States by removing restrictive barriers.

This paper included more than 30,000 patients with opioid use disorder and showed those on methadone were almost 60% significantly less likely to stop treatment at 24 months than their peers assigned to buprenorphine/naloxone (adjusted hazard ratio [aHR], 1.58), with no difference in mortality risk (aHR, 0.57).

“In Canada, unlike the US, methadone and buprenorphine/naloxone are both available in office-based settings. Methadone really outperforms buprenorphine/naloxone in being able to retain people in treatment, which is our main goal and comes with a host of benefits,” Bohdan Nosyk, PhD, with Simon Fraser University in Burnaby, British Columbia, Canada, who worked on the study, said in an interview.

In addition, a recent systematic review and meta-analysis of relevant research involving more than 1 million patients with opioid use disorder also showed better treatment retention with methadone than with buprenorphine.

During the COVID-19 pandemic, relaxed methadone regulations, that included take-home medications, did not lead to an increase in overdoses. Instead, these changes improved treatment retention and patient experiences, highlighting the potential benefits of further deregulation.
 

‘Atrocious’ Outdated Policies

However, despite methadone’s proven efficacy and safety for opioid use disorder, it remains vastly underutilized because of outdated US policies restricting its use to opioid treatment programs (OTPs).

“It’s absolutely atrocious that methadone policies have not kept up with the evidence. If you look at other countries that have expanded their access to methadone, their overdose rates have fallen dramatically,” said Leslie Suen, MD, with the University of California, San Francisco, and coauthor of a recent JAMA Viewpoint on this topic.

“Methadone is a very good medication that’s been shown over and over to be very effective and safe,” Alan Leshner, PhD, past director of the National Institute on Drug Abuse, said in an interview.

“There is no reason why it couldn’t be administered through pharmacies or through physicians’ offices as long as it’s done in a controlled and careful way,” said Leshner.

Leshner chaired the committee that produced the 2019 report Medications for Opioid Use Disorder Save Lives.

“We learned during COVID that increasing the amount of take-home methadone and increasing access does not lead to an increase in deaths or an increase in overdose, so it’s hard to find a reason not to do it,” he said.
 

Change Finally on the Horizon?

Several recent and proposed policy changes could revolutionize methadone delivery in the United States.

In March 2022, in response to the pandemic, the Drug Enforcement Administration (DEA) allowed hospitals to dispense up to a 3-day supply of methadone (known as the 72-hour rule) to bridge care transitions without needing OTPs.

In April 2024, the Substance Abuse and Mental Health Services Administration and DEA codified many methadone and buprenorphine delivery flexibilities granted temporarily during the pandemic, including increased use of telehealth assessments and earlier access to take-home methadone doses.

Another contemporary policy change is expansion of the Americans with Disabilities Act mandating that patients taking medications for opioid use disorder, such as methadone, be able to continue treatment when transitioning to settings such as hospitals, jails, and skilled nursing facilities.

At the state level, California Governor Gavin Newsom recently signed a bill, effective immediately, that expands access to methadone treatment in his state.

On the horizon at the federal level is the Modernizing Opioid Treatment Access Act (MOTAA) — the bipartisan and bicameral bill introduced by Sen. Ed Markey (D-MA) and Sen. Rand Paul (R-KY), along with Rep. Donald Norcross (D-NJ) and Rep. Don Bacon, (R-NE) — that would allow methadone to be prescribed by addiction specialists and dispensed in community pharmacies.
 

An Ethical Imperative

“With only about 2000 OTP clinics clustered in urban areas, less than 25% of people who are diagnosed with opioid use disorder are actually able to access methadone,” Caty Simon, with the National Survivors Union, Greensboro, North Carolina, and coauthor of the JAMA Viewpoint, said in an interview.

While MOTAA represents a major step forward, limiting methadone prescribing to addiction specialists may not fully address the treatment gap, particularly in rural and underserved areas, Simon said.

To optimize methadone’s potential, she’d like to see further expansion of prescribing privileges to general healthcare providers.

“As someone with lived and living experience of opioid use and treatment, and somebody who works nationally and locally in organizations of people impacted by drug use, I know people in my area right now — marginalized people of color — who would have much better chances of survival if they were able to access methadone. If MOTAA passed tomorrow, we could save so many lives. There is an ethical imperative to pass it,” Simon said.

Leshner said he is “always very concerned about access, particularly for underserved populations, poor people, people living in rural areas. If you can access the medications you need, you’re in big trouble.”

Is this methadone’s moment? “I’m a little optimistic, but I haven’t seen the progress I would like to see,” Leshner said.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved a 10-mg dose of Roxybond (Protega Pharmaceuticals), an opioid analgesic indicated for the management of severe pain in cases where other treatments are not well-tolerated or prove ineffective.

Roxybond, an immediate-release (IR) formulation of oxycodone hydrochloride, is made with Protega’s SentryBond technology, which makes it harder for people to crush, inject, or snort, according to the company.

In a statement from Protega, Paul Howe, the company’s chief commercial officer, said the drug meets an “unmet need for an IR opioid with abuse-deterrent technology that may reduce misuse and abuse while providing pain relief to medically appropriate patients when used as indicated.”

To determine the tablet’s ability to withstand manipulation, more than 2000 in vitro tests were conducted, according to the release. The findings indicate Roxybond reduces — but does not entirely negate — the potential for intranasal and intravenous abuse.

Roxybond was previously approved in 5-, 15-, and 30-mg doses. The 10 mg option provides clinicians with the ability to better modify side effects, manage titration, and provide precision care for patients on opioid therapy, according to Protega.

“For patients, the range of doses can provide better pain control, reduce the risk of side effects, and provide a smoother transition during dosing transitions,” the company stated.

Roxybond is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma, gastrointestinal obstruction, or hypersensitivity to oxycodone. The drug is not intended for long-term use unless otherwise determined by a clinician. Roxybond also is subject to the FDA’s Risk Evaluation and Mitigation Strategies for opioids.

“The development of Roxybond with SentryBond is a step forward in fighting the national epidemic of prescription opioid overdose,” said Eric Kinzler, PhD, vice president of medical and regulatory affairs for Protega, in a release. “Protega is dedicated to our mission to block the path to abuse and work with healthcare professionals across the continuum of care to reduce misuse and abuse.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved a 10-mg dose of Roxybond (Protega Pharmaceuticals), an opioid analgesic indicated for the management of severe pain in cases where other treatments are not well-tolerated or prove ineffective.

Roxybond, an immediate-release (IR) formulation of oxycodone hydrochloride, is made with Protega’s SentryBond technology, which makes it harder for people to crush, inject, or snort, according to the company.

In a statement from Protega, Paul Howe, the company’s chief commercial officer, said the drug meets an “unmet need for an IR opioid with abuse-deterrent technology that may reduce misuse and abuse while providing pain relief to medically appropriate patients when used as indicated.”

To determine the tablet’s ability to withstand manipulation, more than 2000 in vitro tests were conducted, according to the release. The findings indicate Roxybond reduces — but does not entirely negate — the potential for intranasal and intravenous abuse.

Roxybond was previously approved in 5-, 15-, and 30-mg doses. The 10 mg option provides clinicians with the ability to better modify side effects, manage titration, and provide precision care for patients on opioid therapy, according to Protega.

“For patients, the range of doses can provide better pain control, reduce the risk of side effects, and provide a smoother transition during dosing transitions,” the company stated.

Roxybond is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma, gastrointestinal obstruction, or hypersensitivity to oxycodone. The drug is not intended for long-term use unless otherwise determined by a clinician. Roxybond also is subject to the FDA’s Risk Evaluation and Mitigation Strategies for opioids.

“The development of Roxybond with SentryBond is a step forward in fighting the national epidemic of prescription opioid overdose,” said Eric Kinzler, PhD, vice president of medical and regulatory affairs for Protega, in a release. “Protega is dedicated to our mission to block the path to abuse and work with healthcare professionals across the continuum of care to reduce misuse and abuse.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved a 10-mg dose of Roxybond (Protega Pharmaceuticals), an opioid analgesic indicated for the management of severe pain in cases where other treatments are not well-tolerated or prove ineffective.

Roxybond, an immediate-release (IR) formulation of oxycodone hydrochloride, is made with Protega’s SentryBond technology, which makes it harder for people to crush, inject, or snort, according to the company.

In a statement from Protega, Paul Howe, the company’s chief commercial officer, said the drug meets an “unmet need for an IR opioid with abuse-deterrent technology that may reduce misuse and abuse while providing pain relief to medically appropriate patients when used as indicated.”

To determine the tablet’s ability to withstand manipulation, more than 2000 in vitro tests were conducted, according to the release. The findings indicate Roxybond reduces — but does not entirely negate — the potential for intranasal and intravenous abuse.

Roxybond was previously approved in 5-, 15-, and 30-mg doses. The 10 mg option provides clinicians with the ability to better modify side effects, manage titration, and provide precision care for patients on opioid therapy, according to Protega.

“For patients, the range of doses can provide better pain control, reduce the risk of side effects, and provide a smoother transition during dosing transitions,” the company stated.

Roxybond is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma, gastrointestinal obstruction, or hypersensitivity to oxycodone. The drug is not intended for long-term use unless otherwise determined by a clinician. Roxybond also is subject to the FDA’s Risk Evaluation and Mitigation Strategies for opioids.

“The development of Roxybond with SentryBond is a step forward in fighting the national epidemic of prescription opioid overdose,” said Eric Kinzler, PhD, vice president of medical and regulatory affairs for Protega, in a release. “Protega is dedicated to our mission to block the path to abuse and work with healthcare professionals across the continuum of care to reduce misuse and abuse.”

A version of this article first appeared on Medscape.com.

TOPLINE:

Allogeneic bone marrow–derived mesenchymal stromal cells (BM-MSCs) are safe but do not show efficacy in treating intervertebral disc degeneration (IDD) in patients with chronic low back pain.

METHODOLOGY:

• The RESPINE trial assessed the efficacy and safety of a single intradiscal injection of allogeneic BM-MSCs in the treatment of chronic low back pain caused by single-level IDD.
• Overall, 114 patients (mean age, 40.9 years; 35% women) with IDD-associated chronic low back pain that was persistent for 3 months or more despite conventional medical therapy and without previous surgery, were recruited across four European countries from April 2018 to April 2021 and randomly assigned to receive either intradiscal injections of allogeneic BM-MSCs (n = 58) or sham injections (n = 56).
• The first co-primary endpoint was the rate of response to BM-MSC injections at 12 months after treatment, defined as improvement of at least 20% or 20 mm in the Visual Analog Scale for pain or improvement of at least 20% in the Oswestry Disability Index for functional status.
• The secondary co-primary endpoint was structural efficacy, based on disc fluid content measured by quantitative T2 MRI between baseline and month 12.

TAKEAWAY:

• At 12 months post-intervention, 74% of patients in the BM-MSC group were classified as responders compared with 68.8% in the placebo group. However, the difference between the groups was not statistically significant.
• The probability of being a responder was higher in the BM-MSC group than in the sham group; however, the findings did not reach statistical significance.
• The average change in disc fluid content, indicative of disc regeneration, from baseline to 12 months was 37.9% in the BM-MSC group and 41.7% in the placebo group, with no significant difference between the groups.
• The incidence of adverse events and serious adverse events was not significantly different between the treatment groups.

IN PRACTICE:

“BM-MSC represents a promising opportunity for the biological treatment of IDD, but only high-quality randomized controlled trials, comparing it to standard care, can determine whether it is a truly effective alternative to spine fusion or disc replacement,” the authors wrote.

SOURCE:

The study was led by Yves-Marie Pers, MD, PhD, Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, CHRU Lapeyronie, Montpellier, France. It was published online on October 11, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

MRI results were collected from only 55 patients across both trial arms, which may have affected the statistical power of the findings. Although patients were monitored for up to 24 months, the long-term efficacy and safety of BM-MSC therapy for IDD may not have been fully captured. Selection bias could not be excluded because of the difficulty in accurately identifying patients with chronic low back pain caused by single-level IDD.

DISCLOSURES:

The study was funded by the European Union’s Horizon 2020 Research and Innovation Programme. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Allogeneic bone marrow–derived mesenchymal stromal cells (BM-MSCs) are safe but do not show efficacy in treating intervertebral disc degeneration (IDD) in patients with chronic low back pain.

METHODOLOGY:

• The RESPINE trial assessed the efficacy and safety of a single intradiscal injection of allogeneic BM-MSCs in the treatment of chronic low back pain caused by single-level IDD.
• Overall, 114 patients (mean age, 40.9 years; 35% women) with IDD-associated chronic low back pain that was persistent for 3 months or more despite conventional medical therapy and without previous surgery, were recruited across four European countries from April 2018 to April 2021 and randomly assigned to receive either intradiscal injections of allogeneic BM-MSCs (n = 58) or sham injections (n = 56).
• The first co-primary endpoint was the rate of response to BM-MSC injections at 12 months after treatment, defined as improvement of at least 20% or 20 mm in the Visual Analog Scale for pain or improvement of at least 20% in the Oswestry Disability Index for functional status.
• The secondary co-primary endpoint was structural efficacy, based on disc fluid content measured by quantitative T2 MRI between baseline and month 12.

TAKEAWAY:

• At 12 months post-intervention, 74% of patients in the BM-MSC group were classified as responders compared with 68.8% in the placebo group. However, the difference between the groups was not statistically significant.
• The probability of being a responder was higher in the BM-MSC group than in the sham group; however, the findings did not reach statistical significance.
• The average change in disc fluid content, indicative of disc regeneration, from baseline to 12 months was 37.9% in the BM-MSC group and 41.7% in the placebo group, with no significant difference between the groups.
• The incidence of adverse events and serious adverse events was not significantly different between the treatment groups.

IN PRACTICE:

“BM-MSC represents a promising opportunity for the biological treatment of IDD, but only high-quality randomized controlled trials, comparing it to standard care, can determine whether it is a truly effective alternative to spine fusion or disc replacement,” the authors wrote.

SOURCE:

The study was led by Yves-Marie Pers, MD, PhD, Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, CHRU Lapeyronie, Montpellier, France. It was published online on October 11, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

MRI results were collected from only 55 patients across both trial arms, which may have affected the statistical power of the findings. Although patients were monitored for up to 24 months, the long-term efficacy and safety of BM-MSC therapy for IDD may not have been fully captured. Selection bias could not be excluded because of the difficulty in accurately identifying patients with chronic low back pain caused by single-level IDD.

DISCLOSURES:

The study was funded by the European Union’s Horizon 2020 Research and Innovation Programme. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Allogeneic bone marrow–derived mesenchymal stromal cells (BM-MSCs) are safe but do not show efficacy in treating intervertebral disc degeneration (IDD) in patients with chronic low back pain.

METHODOLOGY:

• The RESPINE trial assessed the efficacy and safety of a single intradiscal injection of allogeneic BM-MSCs in the treatment of chronic low back pain caused by single-level IDD.
• Overall, 114 patients (mean age, 40.9 years; 35% women) with IDD-associated chronic low back pain that was persistent for 3 months or more despite conventional medical therapy and without previous surgery, were recruited across four European countries from April 2018 to April 2021 and randomly assigned to receive either intradiscal injections of allogeneic BM-MSCs (n = 58) or sham injections (n = 56).
• The first co-primary endpoint was the rate of response to BM-MSC injections at 12 months after treatment, defined as improvement of at least 20% or 20 mm in the Visual Analog Scale for pain or improvement of at least 20% in the Oswestry Disability Index for functional status.
• The secondary co-primary endpoint was structural efficacy, based on disc fluid content measured by quantitative T2 MRI between baseline and month 12.

TAKEAWAY:

• At 12 months post-intervention, 74% of patients in the BM-MSC group were classified as responders compared with 68.8% in the placebo group. However, the difference between the groups was not statistically significant.
• The probability of being a responder was higher in the BM-MSC group than in the sham group; however, the findings did not reach statistical significance.
• The average change in disc fluid content, indicative of disc regeneration, from baseline to 12 months was 37.9% in the BM-MSC group and 41.7% in the placebo group, with no significant difference between the groups.
• The incidence of adverse events and serious adverse events was not significantly different between the treatment groups.

IN PRACTICE:

“BM-MSC represents a promising opportunity for the biological treatment of IDD, but only high-quality randomized controlled trials, comparing it to standard care, can determine whether it is a truly effective alternative to spine fusion or disc replacement,” the authors wrote.

SOURCE:

The study was led by Yves-Marie Pers, MD, PhD, Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, CHRU Lapeyronie, Montpellier, France. It was published online on October 11, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

MRI results were collected from only 55 patients across both trial arms, which may have affected the statistical power of the findings. Although patients were monitored for up to 24 months, the long-term efficacy and safety of BM-MSC therapy for IDD may not have been fully captured. Selection bias could not be excluded because of the difficulty in accurately identifying patients with chronic low back pain caused by single-level IDD.

DISCLOSURES:

The study was funded by the European Union’s Horizon 2020 Research and Innovation Programme. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has announced a voluntary manufacturer-initiated recall of more than 7000 bottles of duloxetine delayed-release capsules due to unacceptable levels of a potential carcinogen.

Duloxetine (Cymbalta) is a serotonin-norepinephrine reuptake inhibitor used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, chronic musculoskeletal pain, and neuropathic pain associated with diabetic peripheral neuropathy.

The recall is due to the detection of the nitrosamine impurity, N-nitroso duloxetine, above the proposed interim limit.

Nitrosamines are common in water and foods, and exposure to some levels of the chemical is common. Exposure to nitrosamine impurities above acceptable levels and over long periods may increase cancer risk, the FDA reported.

“If drugs contain levels of nitrosamines above the acceptable daily intake limits, FDA recommends these drugs be recalled by the manufacturer as appropriate,” the agency noted on its website.

The recall was initiated by Breckenridge Pharmaceutical and covers 7107 bottles of 500-count, 20 mg duloxetine delayed-release capsules. The drug is manufactured by Towa Pharmaceutical Europe and distributed nationwide by BPI.

The affected bottles are from lot number 220128 with an expiration date of 12/2024 and NDC of 51991-746-05.

The recall was initiated on October 10 and is ongoing.

“Healthcare professionals can educate patients about alternative treatment options to medications with potential nitrosamine impurities if available and clinically appropriate,” the FDA advises. “If a medication has been recalled, pharmacists may be able to dispense the same medication from a manufacturing lot that has not been recalled. Prescribers may also determine whether there is an alternative treatment option for patients.”

The FDA has labeled this a “class II” recall, which the agency defines as “a situation in which use of or exposure to a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote.”

Nitrosamine impurities have prompted a number of drug recalls in recent years, including oral anticoagulants, metformin, and skeletal muscle relaxants.

The impurities may be found in drugs for a number of reasons, the agency reported. The source may be from a drug’s manufacturing process, chemical structure, or the conditions under which it is stored or packaged.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has announced a voluntary manufacturer-initiated recall of more than 7000 bottles of duloxetine delayed-release capsules due to unacceptable levels of a potential carcinogen.

Duloxetine (Cymbalta) is a serotonin-norepinephrine reuptake inhibitor used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, chronic musculoskeletal pain, and neuropathic pain associated with diabetic peripheral neuropathy.

The recall is due to the detection of the nitrosamine impurity, N-nitroso duloxetine, above the proposed interim limit.

Nitrosamines are common in water and foods, and exposure to some levels of the chemical is common. Exposure to nitrosamine impurities above acceptable levels and over long periods may increase cancer risk, the FDA reported.

“If drugs contain levels of nitrosamines above the acceptable daily intake limits, FDA recommends these drugs be recalled by the manufacturer as appropriate,” the agency noted on its website.

The recall was initiated by Breckenridge Pharmaceutical and covers 7107 bottles of 500-count, 20 mg duloxetine delayed-release capsules. The drug is manufactured by Towa Pharmaceutical Europe and distributed nationwide by BPI.

The affected bottles are from lot number 220128 with an expiration date of 12/2024 and NDC of 51991-746-05.

The recall was initiated on October 10 and is ongoing.

“Healthcare professionals can educate patients about alternative treatment options to medications with potential nitrosamine impurities if available and clinically appropriate,” the FDA advises. “If a medication has been recalled, pharmacists may be able to dispense the same medication from a manufacturing lot that has not been recalled. Prescribers may also determine whether there is an alternative treatment option for patients.”

The FDA has labeled this a “class II” recall, which the agency defines as “a situation in which use of or exposure to a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote.”

Nitrosamine impurities have prompted a number of drug recalls in recent years, including oral anticoagulants, metformin, and skeletal muscle relaxants.

The impurities may be found in drugs for a number of reasons, the agency reported. The source may be from a drug’s manufacturing process, chemical structure, or the conditions under which it is stored or packaged.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has announced a voluntary manufacturer-initiated recall of more than 7000 bottles of duloxetine delayed-release capsules due to unacceptable levels of a potential carcinogen.

Duloxetine (Cymbalta) is a serotonin-norepinephrine reuptake inhibitor used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, chronic musculoskeletal pain, and neuropathic pain associated with diabetic peripheral neuropathy.

The recall is due to the detection of the nitrosamine impurity, N-nitroso duloxetine, above the proposed interim limit.

Nitrosamines are common in water and foods, and exposure to some levels of the chemical is common. Exposure to nitrosamine impurities above acceptable levels and over long periods may increase cancer risk, the FDA reported.

“If drugs contain levels of nitrosamines above the acceptable daily intake limits, FDA recommends these drugs be recalled by the manufacturer as appropriate,” the agency noted on its website.

The recall was initiated by Breckenridge Pharmaceutical and covers 7107 bottles of 500-count, 20 mg duloxetine delayed-release capsules. The drug is manufactured by Towa Pharmaceutical Europe and distributed nationwide by BPI.

The affected bottles are from lot number 220128 with an expiration date of 12/2024 and NDC of 51991-746-05.

The recall was initiated on October 10 and is ongoing.

“Healthcare professionals can educate patients about alternative treatment options to medications with potential nitrosamine impurities if available and clinically appropriate,” the FDA advises. “If a medication has been recalled, pharmacists may be able to dispense the same medication from a manufacturing lot that has not been recalled. Prescribers may also determine whether there is an alternative treatment option for patients.”

The FDA has labeled this a “class II” recall, which the agency defines as “a situation in which use of or exposure to a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote.”

Nitrosamine impurities have prompted a number of drug recalls in recent years, including oral anticoagulants, metformin, and skeletal muscle relaxants.

The impurities may be found in drugs for a number of reasons, the agency reported. The source may be from a drug’s manufacturing process, chemical structure, or the conditions under which it is stored or packaged.
 

A version of this article appeared on Medscape.com.

Sarah, a new mom who’s thrilled about her 3-month-old baby, is struggling with her sex life. Her once vibrant physical relationship with her partner has dwindled, and she’s dealing with painful intercourse and a notable drop in desire.

Pregnancy and childbirth are transformative experiences that affect every facet of a person’s life, including their sexual well-being. Despite this fact, clinicians frequently ignore sexual well-being, beyond contraception, in prenatal and postpartum care. In peripartum care, anticipatory guidance is recognized to be crucial to the well-being of new parents and their babies. Why should sexual well-being get the shaft? 
 

Why Talk About Sex?

Sex is a fundamental aspect of many people’s lives and relationships and can significantly affect overall well-being. Despite cultural narratives that often exclude the sexual function and pleasure aspect of sexual health from peripartum discussions, many new parents face sexual challenges that can worsen their physical and emotional health.

While up to 88% of new parents report problems with sexual well-being, less than 30% report receiving anticipatory guidance about sexual function changes. One study found only 15% of postpartum women reported discussing sexual concerns with their medical providers. And, when new parents receive more information about sexual health, they tend to report improved sexual well-being. Clearly, a gap needs bridging.

Sexual health doesn’t just affect individual well-being; it intertwines with relationship satisfaction. Attending to satisfaction in one’s relationship may be an important component of child health as well. 

Declines in the frequency of sexual engagement and desire are common after childbirth. Changes in arousal, orgasm, and sexual pleasure, often accompanied by pain, are also reported by many women. Some birthing parents report changes to the sensation of their genitals that are thought to be related to stretch of the pudendal nerve during parturition. Most experience resolution of these concerns within the first year after childbirth, although some women report persistent problems, including up to 33% with persistent sexual pain.

Many factors can contribute to postpartum sexual issues, including hormonal changes, body image concerns, and mental health conditions. Breastfeeding, for instance, can lead to vaginal dryness and reduced sexual arousal due to hormonal shifts. Body image issues and mood disorders like depression and anxiety can also adversely affect sexual function. Women with postpartum depression are more likely to experience sexual concerns, and the relationship between sexual difficulties and depression can be bidirectional.
 

Empowerment and Expectations

One commonly cited recommendation is to wait until 6 weeks postpartum before resuming penetrative intercourse after a normal vaginal delivery. However, this guideline lacks robust scientific backing. Many people might feel ready for sexual intercourse much sooner or, conversely, might not feel comfortable at the 6-week mark. As clinicians, we must empower our patients to trust their own bodies and make decisions based on their comfort and readiness.

The 6-week advice can sometimes unintentionally convey to women that they are not experts on their own bodies, or that any kind of sex is risky. Acknowledging the recovery timeline for every person is unique and various forms of sexual expression are safe can help foster a healthier approach to resuming sexual activities. In one study of postpartum sexual behavior, in the first 6 weeks after delivery, the most common kinds of sexual play included giving oral sex to a partner and solo sex. Between 80% and 90% have resumed vaginal-receiving sexual play (including intercourse) by 3 months. 

While recognizing that changes to sexual experience occur, we need to reinforce that gradual recovery is expected. And if women express distress about a sexual change, or if those changes persist, primary care providers should be prepared to help them with their concerns. 

Parents need to know experiencing pain is not something they should “just deal with” or ignore. Attempting to repeatedly endure sexual pain can cause new issues, such as high-tone dysfunction of the pelvic floor or an understandable decrease in willingness or receptiveness to sexual play of any kind. Encouraging open communication about these issues can help couples navigate these changes more smoothly.

Partners, especially new fathers, also experience sexual and emotional challenges. They can feel blindsided by the changes in their relationship and might struggle with feelings of jealousy or inadequacy. Understanding partners also face difficulties can help in providing a more comprehensive approach to sexual health care.
 

Starting the Conversation

So, how can we initiate these important conversations with new parents? Start by providing permission. As healthcare providers, we need to create an environment where discussing sexual health is normalized and welcomed. Simple, nonjudgmental statements can open the door to these discussions. For example, saying, “Many people notice changes in their sexual desire or pleasure after childbirth. Has anything like this happened to you or your partner?” can encourage patients to share their concerns.

Assessing the importance to patients of sexual problems can help direct the need for intervention. Follow up on these concerns and offer support, whether through counseling, pelvic floor physical therapy, or a referral to a sexual medicine specialist, a sex therapist, or other appropriate resource.

Let’s return to Sarah. In the ideal world, at 3 months postpartum she will already have had a handful of clinical conversations about her sexual well-being with her healthcare team — at prenatal visits, at well-baby visits, and at her postpartum checkups. Several of these conversations included her partner. They both understand the transition to parenthood could be rocky for their sex lives. They’ve set aside time to connect and stay physically close. She’s listened to her body and only engaged in sexual play for which she feels ready. Now, noting that some aspects of sexual play are persistently uncomfortable, she knows it’s time to follow up. Without shame or anxiety, she books an appointment with you, knowing that you understand how important this issue is for her, her partner, and her baby. 

If you’re working with new parents, remember: Open dialogue about sexual health is not just beneficial — it’s essential. Let’s bridge the gap in care by embracing these conversations and offering the support new parents truly need.
 

Dr. Kranz, Clinical Assistant Professor of Obstetrics/Gynecology and Family Medicine, University of Rochester Medical Center, Rochester, New York, has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Sarah, a new mom who’s thrilled about her 3-month-old baby, is struggling with her sex life. Her once vibrant physical relationship with her partner has dwindled, and she’s dealing with painful intercourse and a notable drop in desire.

Pregnancy and childbirth are transformative experiences that affect every facet of a person’s life, including their sexual well-being. Despite this fact, clinicians frequently ignore sexual well-being, beyond contraception, in prenatal and postpartum care. In peripartum care, anticipatory guidance is recognized to be crucial to the well-being of new parents and their babies. Why should sexual well-being get the shaft? 
 

Why Talk About Sex?

Sex is a fundamental aspect of many people’s lives and relationships and can significantly affect overall well-being. Despite cultural narratives that often exclude the sexual function and pleasure aspect of sexual health from peripartum discussions, many new parents face sexual challenges that can worsen their physical and emotional health.

While up to 88% of new parents report problems with sexual well-being, less than 30% report receiving anticipatory guidance about sexual function changes. One study found only 15% of postpartum women reported discussing sexual concerns with their medical providers. And, when new parents receive more information about sexual health, they tend to report improved sexual well-being. Clearly, a gap needs bridging.

Sexual health doesn’t just affect individual well-being; it intertwines with relationship satisfaction. Attending to satisfaction in one’s relationship may be an important component of child health as well. 

Declines in the frequency of sexual engagement and desire are common after childbirth. Changes in arousal, orgasm, and sexual pleasure, often accompanied by pain, are also reported by many women. Some birthing parents report changes to the sensation of their genitals that are thought to be related to stretch of the pudendal nerve during parturition. Most experience resolution of these concerns within the first year after childbirth, although some women report persistent problems, including up to 33% with persistent sexual pain.

Many factors can contribute to postpartum sexual issues, including hormonal changes, body image concerns, and mental health conditions. Breastfeeding, for instance, can lead to vaginal dryness and reduced sexual arousal due to hormonal shifts. Body image issues and mood disorders like depression and anxiety can also adversely affect sexual function. Women with postpartum depression are more likely to experience sexual concerns, and the relationship between sexual difficulties and depression can be bidirectional.
 

Empowerment and Expectations

One commonly cited recommendation is to wait until 6 weeks postpartum before resuming penetrative intercourse after a normal vaginal delivery. However, this guideline lacks robust scientific backing. Many people might feel ready for sexual intercourse much sooner or, conversely, might not feel comfortable at the 6-week mark. As clinicians, we must empower our patients to trust their own bodies and make decisions based on their comfort and readiness.

The 6-week advice can sometimes unintentionally convey to women that they are not experts on their own bodies, or that any kind of sex is risky. Acknowledging the recovery timeline for every person is unique and various forms of sexual expression are safe can help foster a healthier approach to resuming sexual activities. In one study of postpartum sexual behavior, in the first 6 weeks after delivery, the most common kinds of sexual play included giving oral sex to a partner and solo sex. Between 80% and 90% have resumed vaginal-receiving sexual play (including intercourse) by 3 months. 

While recognizing that changes to sexual experience occur, we need to reinforce that gradual recovery is expected. And if women express distress about a sexual change, or if those changes persist, primary care providers should be prepared to help them with their concerns. 

Parents need to know experiencing pain is not something they should “just deal with” or ignore. Attempting to repeatedly endure sexual pain can cause new issues, such as high-tone dysfunction of the pelvic floor or an understandable decrease in willingness or receptiveness to sexual play of any kind. Encouraging open communication about these issues can help couples navigate these changes more smoothly.

Partners, especially new fathers, also experience sexual and emotional challenges. They can feel blindsided by the changes in their relationship and might struggle with feelings of jealousy or inadequacy. Understanding partners also face difficulties can help in providing a more comprehensive approach to sexual health care.
 

Starting the Conversation

So, how can we initiate these important conversations with new parents? Start by providing permission. As healthcare providers, we need to create an environment where discussing sexual health is normalized and welcomed. Simple, nonjudgmental statements can open the door to these discussions. For example, saying, “Many people notice changes in their sexual desire or pleasure after childbirth. Has anything like this happened to you or your partner?” can encourage patients to share their concerns.

Assessing the importance to patients of sexual problems can help direct the need for intervention. Follow up on these concerns and offer support, whether through counseling, pelvic floor physical therapy, or a referral to a sexual medicine specialist, a sex therapist, or other appropriate resource.

Let’s return to Sarah. In the ideal world, at 3 months postpartum she will already have had a handful of clinical conversations about her sexual well-being with her healthcare team — at prenatal visits, at well-baby visits, and at her postpartum checkups. Several of these conversations included her partner. They both understand the transition to parenthood could be rocky for their sex lives. They’ve set aside time to connect and stay physically close. She’s listened to her body and only engaged in sexual play for which she feels ready. Now, noting that some aspects of sexual play are persistently uncomfortable, she knows it’s time to follow up. Without shame or anxiety, she books an appointment with you, knowing that you understand how important this issue is for her, her partner, and her baby. 

If you’re working with new parents, remember: Open dialogue about sexual health is not just beneficial — it’s essential. Let’s bridge the gap in care by embracing these conversations and offering the support new parents truly need.
 

Dr. Kranz, Clinical Assistant Professor of Obstetrics/Gynecology and Family Medicine, University of Rochester Medical Center, Rochester, New York, has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Sarah, a new mom who’s thrilled about her 3-month-old baby, is struggling with her sex life. Her once vibrant physical relationship with her partner has dwindled, and she’s dealing with painful intercourse and a notable drop in desire.

Pregnancy and childbirth are transformative experiences that affect every facet of a person’s life, including their sexual well-being. Despite this fact, clinicians frequently ignore sexual well-being, beyond contraception, in prenatal and postpartum care. In peripartum care, anticipatory guidance is recognized to be crucial to the well-being of new parents and their babies. Why should sexual well-being get the shaft? 
 

Why Talk About Sex?

Sex is a fundamental aspect of many people’s lives and relationships and can significantly affect overall well-being. Despite cultural narratives that often exclude the sexual function and pleasure aspect of sexual health from peripartum discussions, many new parents face sexual challenges that can worsen their physical and emotional health.

While up to 88% of new parents report problems with sexual well-being, less than 30% report receiving anticipatory guidance about sexual function changes. One study found only 15% of postpartum women reported discussing sexual concerns with their medical providers. And, when new parents receive more information about sexual health, they tend to report improved sexual well-being. Clearly, a gap needs bridging.

Sexual health doesn’t just affect individual well-being; it intertwines with relationship satisfaction. Attending to satisfaction in one’s relationship may be an important component of child health as well. 

Declines in the frequency of sexual engagement and desire are common after childbirth. Changes in arousal, orgasm, and sexual pleasure, often accompanied by pain, are also reported by many women. Some birthing parents report changes to the sensation of their genitals that are thought to be related to stretch of the pudendal nerve during parturition. Most experience resolution of these concerns within the first year after childbirth, although some women report persistent problems, including up to 33% with persistent sexual pain.

Many factors can contribute to postpartum sexual issues, including hormonal changes, body image concerns, and mental health conditions. Breastfeeding, for instance, can lead to vaginal dryness and reduced sexual arousal due to hormonal shifts. Body image issues and mood disorders like depression and anxiety can also adversely affect sexual function. Women with postpartum depression are more likely to experience sexual concerns, and the relationship between sexual difficulties and depression can be bidirectional.
 

Empowerment and Expectations

One commonly cited recommendation is to wait until 6 weeks postpartum before resuming penetrative intercourse after a normal vaginal delivery. However, this guideline lacks robust scientific backing. Many people might feel ready for sexual intercourse much sooner or, conversely, might not feel comfortable at the 6-week mark. As clinicians, we must empower our patients to trust their own bodies and make decisions based on their comfort and readiness.

The 6-week advice can sometimes unintentionally convey to women that they are not experts on their own bodies, or that any kind of sex is risky. Acknowledging the recovery timeline for every person is unique and various forms of sexual expression are safe can help foster a healthier approach to resuming sexual activities. In one study of postpartum sexual behavior, in the first 6 weeks after delivery, the most common kinds of sexual play included giving oral sex to a partner and solo sex. Between 80% and 90% have resumed vaginal-receiving sexual play (including intercourse) by 3 months. 

While recognizing that changes to sexual experience occur, we need to reinforce that gradual recovery is expected. And if women express distress about a sexual change, or if those changes persist, primary care providers should be prepared to help them with their concerns. 

Parents need to know experiencing pain is not something they should “just deal with” or ignore. Attempting to repeatedly endure sexual pain can cause new issues, such as high-tone dysfunction of the pelvic floor or an understandable decrease in willingness or receptiveness to sexual play of any kind. Encouraging open communication about these issues can help couples navigate these changes more smoothly.

Partners, especially new fathers, also experience sexual and emotional challenges. They can feel blindsided by the changes in their relationship and might struggle with feelings of jealousy or inadequacy. Understanding partners also face difficulties can help in providing a more comprehensive approach to sexual health care.
 

Starting the Conversation

So, how can we initiate these important conversations with new parents? Start by providing permission. As healthcare providers, we need to create an environment where discussing sexual health is normalized and welcomed. Simple, nonjudgmental statements can open the door to these discussions. For example, saying, “Many people notice changes in their sexual desire or pleasure after childbirth. Has anything like this happened to you or your partner?” can encourage patients to share their concerns.

Assessing the importance to patients of sexual problems can help direct the need for intervention. Follow up on these concerns and offer support, whether through counseling, pelvic floor physical therapy, or a referral to a sexual medicine specialist, a sex therapist, or other appropriate resource.

Let’s return to Sarah. In the ideal world, at 3 months postpartum she will already have had a handful of clinical conversations about her sexual well-being with her healthcare team — at prenatal visits, at well-baby visits, and at her postpartum checkups. Several of these conversations included her partner. They both understand the transition to parenthood could be rocky for their sex lives. They’ve set aside time to connect and stay physically close. She’s listened to her body and only engaged in sexual play for which she feels ready. Now, noting that some aspects of sexual play are persistently uncomfortable, she knows it’s time to follow up. Without shame or anxiety, she books an appointment with you, knowing that you understand how important this issue is for her, her partner, and her baby. 

If you’re working with new parents, remember: Open dialogue about sexual health is not just beneficial — it’s essential. Let’s bridge the gap in care by embracing these conversations and offering the support new parents truly need.
 

Dr. Kranz, Clinical Assistant Professor of Obstetrics/Gynecology and Family Medicine, University of Rochester Medical Center, Rochester, New York, has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: I’m Dr. Rachel Rubin, a urologist and sexual medicine specialist in the Washington, DC, area. And I am so thrilled because my co-fellow, the brilliant and famous Dr. Ashley Winter, a board-certified urologist and a certified menopause practitioner, who sees patients in our practice from Los Angeles, is joining us today to talk about sex as a vital sign.

Ashley Winter, MD: To have the best sexual function, you need many different systems to work. You need your hormones to be in the right place. You need your blood vessels to dilate when you want them to. You need your nerves to connect to your genitalia to make them responsive. The way people say, “The eyes are the window into the soul” — well, the genitals are the window into the cardiovascular system, the peripheral nervous system, and the hormonal system. It’s so dynamic. Patients can understand how this reflects their health. We just need healthcare providers to hammer home how those things connect.

Rubin: If you’re a primary care doctor seeing a patient and you want to educate them on diabetes or high blood pressure, how can you “ ‘sell it with ‘sex”? How can you use sex to educate them about these important medical conditions?

Winter: I hate using it as a fear tactic, but sometimes you have to. Time and again, I’ve seen men with severe profound erectile dysfunction at a young age, with chronically uncontrolled diabetes.

Diabetes can impair the peripheral nerves, resulting in peripheral neuropathy. The same way that it can affect the fingers and toes, diabetes can affect the penis, even before those other areas. Diabetes can also lead to other conditions such as low testosterone, which also affects the function of the penis.

I’m being brutally honest when I tell patients that diabetes control is critical to having a wonderful sexspan — the duration of your life where you’re able to be sexually active and have great sex and do it in the way that you want.

Chronic conditions such as high cholesterol or hypertension can affect your ability to become erect or aroused whether you have a penis or a vulva, and even your ability to have an orgasm.

Rubin: None of my doctors has ever asked me about these issues. But we have to bring them up with patients because they›re not going to bring them up to us. I always say in the review of systems, we shouldn›t just ask, “Do you have any sexual problems?” (which nobody ever does) and move past the question about men, women or both. We should be asking, “Do you have any issues with libido? Do you want to talk about it? Any issues with erection, arousal, orgasm, or sexual pain?”

When you can talk about those things, you can treat the patient from a whole physiologic perspective. For example, how does their sciatica affect their sexual pain? How does their antidepressant cause a delayed orgasm? How does their low testosterone level affect their energy level, their libido, and their desire? 

We see so much shame and guilt in sexual health, to the extent that patients feel broken. We can help them understand the anatomy and physiology and explain that they aren’t broken. Instead, it’s “You need this medicine for your crippling anxiety, and that’s why your orgasm is delayed, and so can we augment it or add or subtract something to help you with it.”

Winter: In a primary care setting, where we are considering the patient›s overall health, we strive for medication compliance, but a huge part of medication noncompliance is sexual side effects, whether it›s antidepressants, beta-blockers, birth control, or this new world of GLP-1 agonists.

Rubin: I would add breast cancer treatments. Many patients go off their anastrozole or their tamoxifen because of the sexual side effects. 

Winter: This is where we get to the crux of this discussion about sex being a vital sign — something you need to check routinely. We need to become comfortable with it, because then we are unlocking the ability to treat every patient like a whole person, give them better outcomes, improve their compliance, and have a really powerful tool for education.

Rubin: We have a growing toolbox for all genders when it comes to sexual health. We have FDA- approved medications for low libido in women. We use testosterone in men in an evidence-based way to safely improve libido. We use medications to help with the genitourinary syndrome of menopause. Orgasm is a challenging one, but we have devices that can help with those reflexes. And working with people who specialize in sexual pain can be extremely helpful for patients.

Dr. Winter, having practiced in different settings, what would you tell the primary care doctors who don’t want to talk about libido or who minimize sexual complaints because they don’t know how to navigate them?

Winter: I do not envy the challenge of being a primary care provider in the healthcare world we are living in. I think it is the hardest job. The ultimate takeaway is to just normalize the conversation and be able to validate what is happening. Have a few basic tools, and then have referrals. It›s not that you have to have all the time in the world or you have to treat every condition, but you have to start the conversation, be comfortable with it, and then get patients hooked up with the right resources.

Rubin: Every doctor of every kind can connect with patients and try to understand what they care about. What are their goals? What do they want for their families, for their relationships, for their quality of life? And how can we work collaboratively as a team to help them with those things? 

Sex is a huge part of people’s lives. If we don’t ask about it; if we don’t look into it; and if we don’t admit that our physiology, our medications, and our surgeries can affect sexual health and functioning, how can we improve people’s lives? We can do so much as a team when we consider sex as a true vital sign.
 

Dr. Rubin, Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC, has disclosed ties with Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: I’m Dr. Rachel Rubin, a urologist and sexual medicine specialist in the Washington, DC, area. And I am so thrilled because my co-fellow, the brilliant and famous Dr. Ashley Winter, a board-certified urologist and a certified menopause practitioner, who sees patients in our practice from Los Angeles, is joining us today to talk about sex as a vital sign.

Ashley Winter, MD: To have the best sexual function, you need many different systems to work. You need your hormones to be in the right place. You need your blood vessels to dilate when you want them to. You need your nerves to connect to your genitalia to make them responsive. The way people say, “The eyes are the window into the soul” — well, the genitals are the window into the cardiovascular system, the peripheral nervous system, and the hormonal system. It’s so dynamic. Patients can understand how this reflects their health. We just need healthcare providers to hammer home how those things connect.

Rubin: If you’re a primary care doctor seeing a patient and you want to educate them on diabetes or high blood pressure, how can you “ ‘sell it with ‘sex”? How can you use sex to educate them about these important medical conditions?

Winter: I hate using it as a fear tactic, but sometimes you have to. Time and again, I’ve seen men with severe profound erectile dysfunction at a young age, with chronically uncontrolled diabetes.

Diabetes can impair the peripheral nerves, resulting in peripheral neuropathy. The same way that it can affect the fingers and toes, diabetes can affect the penis, even before those other areas. Diabetes can also lead to other conditions such as low testosterone, which also affects the function of the penis.

I’m being brutally honest when I tell patients that diabetes control is critical to having a wonderful sexspan — the duration of your life where you’re able to be sexually active and have great sex and do it in the way that you want.

Chronic conditions such as high cholesterol or hypertension can affect your ability to become erect or aroused whether you have a penis or a vulva, and even your ability to have an orgasm.

Rubin: None of my doctors has ever asked me about these issues. But we have to bring them up with patients because they›re not going to bring them up to us. I always say in the review of systems, we shouldn›t just ask, “Do you have any sexual problems?” (which nobody ever does) and move past the question about men, women or both. We should be asking, “Do you have any issues with libido? Do you want to talk about it? Any issues with erection, arousal, orgasm, or sexual pain?”

When you can talk about those things, you can treat the patient from a whole physiologic perspective. For example, how does their sciatica affect their sexual pain? How does their antidepressant cause a delayed orgasm? How does their low testosterone level affect their energy level, their libido, and their desire? 

We see so much shame and guilt in sexual health, to the extent that patients feel broken. We can help them understand the anatomy and physiology and explain that they aren’t broken. Instead, it’s “You need this medicine for your crippling anxiety, and that’s why your orgasm is delayed, and so can we augment it or add or subtract something to help you with it.”

Winter: In a primary care setting, where we are considering the patient›s overall health, we strive for medication compliance, but a huge part of medication noncompliance is sexual side effects, whether it›s antidepressants, beta-blockers, birth control, or this new world of GLP-1 agonists.

Rubin: I would add breast cancer treatments. Many patients go off their anastrozole or their tamoxifen because of the sexual side effects. 

Winter: This is where we get to the crux of this discussion about sex being a vital sign — something you need to check routinely. We need to become comfortable with it, because then we are unlocking the ability to treat every patient like a whole person, give them better outcomes, improve their compliance, and have a really powerful tool for education.

Rubin: We have a growing toolbox for all genders when it comes to sexual health. We have FDA- approved medications for low libido in women. We use testosterone in men in an evidence-based way to safely improve libido. We use medications to help with the genitourinary syndrome of menopause. Orgasm is a challenging one, but we have devices that can help with those reflexes. And working with people who specialize in sexual pain can be extremely helpful for patients.

Dr. Winter, having practiced in different settings, what would you tell the primary care doctors who don’t want to talk about libido or who minimize sexual complaints because they don’t know how to navigate them?

Winter: I do not envy the challenge of being a primary care provider in the healthcare world we are living in. I think it is the hardest job. The ultimate takeaway is to just normalize the conversation and be able to validate what is happening. Have a few basic tools, and then have referrals. It›s not that you have to have all the time in the world or you have to treat every condition, but you have to start the conversation, be comfortable with it, and then get patients hooked up with the right resources.

Rubin: Every doctor of every kind can connect with patients and try to understand what they care about. What are their goals? What do they want for their families, for their relationships, for their quality of life? And how can we work collaboratively as a team to help them with those things? 

Sex is a huge part of people’s lives. If we don’t ask about it; if we don’t look into it; and if we don’t admit that our physiology, our medications, and our surgeries can affect sexual health and functioning, how can we improve people’s lives? We can do so much as a team when we consider sex as a true vital sign.
 

Dr. Rubin, Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC, has disclosed ties with Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: I’m Dr. Rachel Rubin, a urologist and sexual medicine specialist in the Washington, DC, area. And I am so thrilled because my co-fellow, the brilliant and famous Dr. Ashley Winter, a board-certified urologist and a certified menopause practitioner, who sees patients in our practice from Los Angeles, is joining us today to talk about sex as a vital sign.

Ashley Winter, MD: To have the best sexual function, you need many different systems to work. You need your hormones to be in the right place. You need your blood vessels to dilate when you want them to. You need your nerves to connect to your genitalia to make them responsive. The way people say, “The eyes are the window into the soul” — well, the genitals are the window into the cardiovascular system, the peripheral nervous system, and the hormonal system. It’s so dynamic. Patients can understand how this reflects their health. We just need healthcare providers to hammer home how those things connect.

Rubin: If you’re a primary care doctor seeing a patient and you want to educate them on diabetes or high blood pressure, how can you “ ‘sell it with ‘sex”? How can you use sex to educate them about these important medical conditions?

Winter: I hate using it as a fear tactic, but sometimes you have to. Time and again, I’ve seen men with severe profound erectile dysfunction at a young age, with chronically uncontrolled diabetes.

Diabetes can impair the peripheral nerves, resulting in peripheral neuropathy. The same way that it can affect the fingers and toes, diabetes can affect the penis, even before those other areas. Diabetes can also lead to other conditions such as low testosterone, which also affects the function of the penis.

I’m being brutally honest when I tell patients that diabetes control is critical to having a wonderful sexspan — the duration of your life where you’re able to be sexually active and have great sex and do it in the way that you want.

Chronic conditions such as high cholesterol or hypertension can affect your ability to become erect or aroused whether you have a penis or a vulva, and even your ability to have an orgasm.

Rubin: None of my doctors has ever asked me about these issues. But we have to bring them up with patients because they›re not going to bring them up to us. I always say in the review of systems, we shouldn›t just ask, “Do you have any sexual problems?” (which nobody ever does) and move past the question about men, women or both. We should be asking, “Do you have any issues with libido? Do you want to talk about it? Any issues with erection, arousal, orgasm, or sexual pain?”

When you can talk about those things, you can treat the patient from a whole physiologic perspective. For example, how does their sciatica affect their sexual pain? How does their antidepressant cause a delayed orgasm? How does their low testosterone level affect their energy level, their libido, and their desire? 

We see so much shame and guilt in sexual health, to the extent that patients feel broken. We can help them understand the anatomy and physiology and explain that they aren’t broken. Instead, it’s “You need this medicine for your crippling anxiety, and that’s why your orgasm is delayed, and so can we augment it or add or subtract something to help you with it.”

Winter: In a primary care setting, where we are considering the patient›s overall health, we strive for medication compliance, but a huge part of medication noncompliance is sexual side effects, whether it›s antidepressants, beta-blockers, birth control, or this new world of GLP-1 agonists.

Rubin: I would add breast cancer treatments. Many patients go off their anastrozole or their tamoxifen because of the sexual side effects. 

Winter: This is where we get to the crux of this discussion about sex being a vital sign — something you need to check routinely. We need to become comfortable with it, because then we are unlocking the ability to treat every patient like a whole person, give them better outcomes, improve their compliance, and have a really powerful tool for education.

Rubin: We have a growing toolbox for all genders when it comes to sexual health. We have FDA- approved medications for low libido in women. We use testosterone in men in an evidence-based way to safely improve libido. We use medications to help with the genitourinary syndrome of menopause. Orgasm is a challenging one, but we have devices that can help with those reflexes. And working with people who specialize in sexual pain can be extremely helpful for patients.

Dr. Winter, having practiced in different settings, what would you tell the primary care doctors who don’t want to talk about libido or who minimize sexual complaints because they don’t know how to navigate them?

Winter: I do not envy the challenge of being a primary care provider in the healthcare world we are living in. I think it is the hardest job. The ultimate takeaway is to just normalize the conversation and be able to validate what is happening. Have a few basic tools, and then have referrals. It›s not that you have to have all the time in the world or you have to treat every condition, but you have to start the conversation, be comfortable with it, and then get patients hooked up with the right resources.

Rubin: Every doctor of every kind can connect with patients and try to understand what they care about. What are their goals? What do they want for their families, for their relationships, for their quality of life? And how can we work collaboratively as a team to help them with those things? 

Sex is a huge part of people’s lives. If we don’t ask about it; if we don’t look into it; and if we don’t admit that our physiology, our medications, and our surgeries can affect sexual health and functioning, how can we improve people’s lives? We can do so much as a team when we consider sex as a true vital sign.
 

Dr. Rubin, Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC, has disclosed ties with Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.

A version of this article first appeared on Medscape.com.

Premenstrual disorders (PMDs), including premenstrual dysphoric disorder (PMDD), adversely affect the lives of millions of women worldwide. Most girls and women — as many as 80%-90%— will experience some premenstrual discomfort such as irritability, depressed mood, food or alcohol cravings, bloating, body aches, breast pain, constipation, or fatigue.

Diagnosable menstrual disorders include, collectively, premenstrual syndrome (PMS); PMDD, formerly called late luteal phase dysphoric disorder; and premenstrual worsening of another medical condition.

The most debilitating of these is PMDD, which has an estimated prevalence of about 4%-8% in women of reproductive age, according to obstetrician/gynecologist Hoosna Haque, MD, assistant professor of medicine at Columbia University Irving Medical Center in New York City.

“It’s difficult to be sure because this condition is underreported,” said Luu D. Ireland, MD, MPH, assistant professor of obstetrics and gynecology at UMass Memorial Medical Center in Worcester, Massachusetts. “But more women are coming forward, and there’s more discussion and media coverage of this condition.”

Occurring in the same post-follicular timeframe as PMS, PMDD takes cyclical discomfort to a more intense level, with a trifecta of affective comorbidities, somatic manifestations, and behavioral changes, all of which can seriously impair daily functioning, including work, physical activities, and personal relationships. Romantic and marital relationships can be particularly impaired.

Although recent cost figures are lacking, PMDs exact a considerable economic toll with increased direct healthcare costs from doctor visits and pharmaceuticals. A 2010 study found that US women with PMS were more likely to accrue in excess of $500 in healthcare visit costs over 2 years, and the figure would likely be higher today. PMDs also increase work/school absenteeism and reduce productivity.
 

Etiology

Brain areas that regulate emotion and behavior contain receptors for estrogen, progesterone, and other sex hormones, which affect the functioning of neurotransmitter systems influencing mood and thinking. Although the precise pathophysiology remains unclear, PMDD is likely multifactorial and results in a heightened sensitivity to normal fluctuations in estrogen and progesterone during the luteal phase of the menstrual cycle and dysfunction of the serotonin and gamma-aminobutyric acid neurotransmitter systems.

Patients with PMDD have lower levels of cortisol and beta-endorphins during both the follicular and luteal phases, suggesting abnormalities in the hypothalamic-pituitary-gonadal axis (HPGA), which is consistent with dysregulation in mood disorders.
 

Risk Factors

These include family history, past traumatic events, smoking, chronic pain syndrome, and obesity. There may be a genetic component as recent studies have suggested the involvement of the gene that codes for the serotonergic 5HT1A receptor and allelic variants of ESR1 in the development of PMS/PMDD.

A particularly concerning aspect of PMDs of any sort is their possible association with a higher risk for death from non-natural causes. In a recent Swedish study, which did not distinguish between PMDs in general and PMDD in particular, patients had an almost 60% greater risk for death from non-natural causes and nearly twice the risk for death by suicide compared with women without PMDs.

Those diagnosed with a PMD at an early age showed excess mortality, and the risk for suicide was elevated regardless of age. “These findings support the need for careful follow-up for young women with PMDs and the need for suicide prevention strategies,” wrote lead author Marion Opatowski, PhD, a medical epidemiologist at Karolinska Institutet in Stockholm, Sweden. “Women with severe PMDD should definitely be monitored for suicidal thoughts or behavior and they should have an emergency outreach plan in place,” Haque added.
 

Diagnosis

Although the somatic manifestations of PMDD resemble those of PMS, they are more severe and associated psychological symptoms are greater. “In my experience, PMDD symptoms can last the whole 2 weeks of the luteal phase, whereas PMS might occur a couple of days before menstruation,” said Ireland.

Symptoms include labile mood, nervousness, hopelessness, anger and aggressiveness, as well as tension and irritability. Those affected may have suicidal thoughts or even behaviors. In addition to a lethargic loss of interest in normal activities, patients with PMDD may feel paranoid, confused, exhausted, or out of control and experience insomnia or hypersomnia. They may have trouble concentrating or remembering. Some patients with PMDD may already be prone to attention-deficit/hyperactivity disorder and non–cycle-related depression, anxiety, and panic attacks.

Diagnosis is based on the presence of any five of the typical affective, somatic, or behavioral symptoms outlined above in the week before onset of menses.

“It’s important to do a careful diagnosis for PMDD and rule out other underlying conditions such as existing depressive or anxiety disorders,” said Haque. “Symptoms tend to be more intense in periods of high hormonal fluctuation such as in the postpartum and perimenopause periods. Women with PMDD should be monitored for postpartum depression.”

PMDD is considered both a gynecologic-genitourinary disorder and an affective condition.

In 2013, it was controversially included as a depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Strongly advocated by some patients, psychiatrists, and pharmaceutical companies, its inclusion was criticized by psychologists and generalists, who feared it would lead to overdiagnosis and pathologization of normal female hormonal changes. Women’s advocates protested that this inclusion would stigmatize female biology and harm their advance in society and the workplace, while some doctors continued to dismiss PMDD as not a serious concern.
 

Treatments

In its latest clinical practice guideline on PMDs, the American College of Obstetricians and Gynecologists (ACOG), for which Ireland served as the lead author, recommends that most patients with PMDD get medical treatment and outlines the following therapies, based on varying degrees of evidence strength.

Antidepressants. These may benefit patients with strong affective symptoms. Selective serotonin reuptake inhibitors such as sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), or fluoxetine (Prozac) are first choices.

Antidepressants may interrupt aberrant signaling in the HPGA, the circuit linking brain and ovaries and regulating the reproductive cycle. Serotonin norepinephrine reuptake inhibitor venlafaxine (Effexor) may also improve symptoms, but other types of antidepressants have not proven effective.

“The response to these well-tolerated drugs is rapid and can happen in the first 2 days,” said Ireland. The drugs may be taken either just in the luteal period or over the month, especially by patients with chronic depression or anxiety.

Hormonal therapy. ACOG recommends the use of combined oral contraceptives (COCs), gonadotropin-releasing hormone (GnRH) agonists to induce anovulation (with combined add-back hormones), progestin-only methods, and noncontraceptive continuous estrogen formulations. It notes, however, that COCs have not been more effective than placebo in reducing depressive symptom scores.

If symptoms do not improve over two to three cycles, an alternate therapy should be considered. Haque recommends an assessment after three cycles and then yearly.

Some women in her practice take both antidepressant and hormone therapy. “Unfortunately, there are no new pharmaceutical treatments on the horizon, but we have good ones already and we would love for patients to utilize them more often,” Ireland said.

Nonsteroidal anti-inflammatory drugs. Limited evidence shows these may reduce physical symptoms such as abdominal cramps, headaches, and general body aches, as well as some mood-related symptoms, which may be an indirect effect of pain alleviation.

Surgery. For women with the most severe intractable symptoms, bilateral oophorectomy with or without hysterectomy may be a last-resort option when medical management has failed. A trial period of GnRH agonist therapy (with or without adjunctive estrogen add-back treatment) is advised before surgery to predict a patient’s response to surgical management.

Acupuncture. ACOG suggests that acupuncture may help manage physical and affective premenstrual symptoms.

Diet. The usual dietary advice for premenstrual symptoms — such as consuming less caffeine, sugar, or alcohol and eating smaller, more frequent meals — is unlikely to help women with PMDD.

Exercise. Although it has not been well studied for PMDD, aerobic exercises such as walking, swimming, and biking tend to improve mood and energy levels in general. Exercise may reduce symptoms through several pathways, including effects on beta-endorphin, cortisol, and ovarian hormone levels.

Supplements. Vitamin B6, calcium and magnesium supplements, and herbal remedies are not supported by consistent or compelling evidence of efficacy. ACOG conditionally recommends calcium supplementation of 100-200 mg/d in adults to help manage physical and affective symptoms.

A small study suggested that supplemental zinc may improve both physical and psychological symptoms.

Cognitive-behavioral therapy. This treatment aims to interrupt negative and irrational thought patterns and may include awareness and education, as well as relaxation techniques, problem-solving and coping skills, and stress management. It has been associated with small to moderate improvement in anxiety and depression, said Ireland.

Peer support. Patients should consider joining a support group. The International Association for Premenstrual Disorders can help patients connect and develop coping skills.

The bottom line is that people with strong symptomatic evidence of PMDD should have medical intervention — to the benefit of their health and quality of life. Screening for PMDD should be part of women’s wellness examinations, said Ireland. “The impact of PMDD should not be minimized or dismissed,” said Haque. “And patients need to know there are very effective treatments.”

Ireland and Haque had no competing interests with regard to their comments.
 

A version of this article first appeared on Medscape.com.

Premenstrual disorders (PMDs), including premenstrual dysphoric disorder (PMDD), adversely affect the lives of millions of women worldwide. Most girls and women — as many as 80%-90%— will experience some premenstrual discomfort such as irritability, depressed mood, food or alcohol cravings, bloating, body aches, breast pain, constipation, or fatigue.

Diagnosable menstrual disorders include, collectively, premenstrual syndrome (PMS); PMDD, formerly called late luteal phase dysphoric disorder; and premenstrual worsening of another medical condition.

The most debilitating of these is PMDD, which has an estimated prevalence of about 4%-8% in women of reproductive age, according to obstetrician/gynecologist Hoosna Haque, MD, assistant professor of medicine at Columbia University Irving Medical Center in New York City.

“It’s difficult to be sure because this condition is underreported,” said Luu D. Ireland, MD, MPH, assistant professor of obstetrics and gynecology at UMass Memorial Medical Center in Worcester, Massachusetts. “But more women are coming forward, and there’s more discussion and media coverage of this condition.”

Occurring in the same post-follicular timeframe as PMS, PMDD takes cyclical discomfort to a more intense level, with a trifecta of affective comorbidities, somatic manifestations, and behavioral changes, all of which can seriously impair daily functioning, including work, physical activities, and personal relationships. Romantic and marital relationships can be particularly impaired.

Although recent cost figures are lacking, PMDs exact a considerable economic toll with increased direct healthcare costs from doctor visits and pharmaceuticals. A 2010 study found that US women with PMS were more likely to accrue in excess of $500 in healthcare visit costs over 2 years, and the figure would likely be higher today. PMDs also increase work/school absenteeism and reduce productivity.
 

Etiology

Brain areas that regulate emotion and behavior contain receptors for estrogen, progesterone, and other sex hormones, which affect the functioning of neurotransmitter systems influencing mood and thinking. Although the precise pathophysiology remains unclear, PMDD is likely multifactorial and results in a heightened sensitivity to normal fluctuations in estrogen and progesterone during the luteal phase of the menstrual cycle and dysfunction of the serotonin and gamma-aminobutyric acid neurotransmitter systems.

Patients with PMDD have lower levels of cortisol and beta-endorphins during both the follicular and luteal phases, suggesting abnormalities in the hypothalamic-pituitary-gonadal axis (HPGA), which is consistent with dysregulation in mood disorders.
 

Risk Factors

These include family history, past traumatic events, smoking, chronic pain syndrome, and obesity. There may be a genetic component as recent studies have suggested the involvement of the gene that codes for the serotonergic 5HT1A receptor and allelic variants of ESR1 in the development of PMS/PMDD.

A particularly concerning aspect of PMDs of any sort is their possible association with a higher risk for death from non-natural causes. In a recent Swedish study, which did not distinguish between PMDs in general and PMDD in particular, patients had an almost 60% greater risk for death from non-natural causes and nearly twice the risk for death by suicide compared with women without PMDs.

Those diagnosed with a PMD at an early age showed excess mortality, and the risk for suicide was elevated regardless of age. “These findings support the need for careful follow-up for young women with PMDs and the need for suicide prevention strategies,” wrote lead author Marion Opatowski, PhD, a medical epidemiologist at Karolinska Institutet in Stockholm, Sweden. “Women with severe PMDD should definitely be monitored for suicidal thoughts or behavior and they should have an emergency outreach plan in place,” Haque added.
 

Diagnosis

Although the somatic manifestations of PMDD resemble those of PMS, they are more severe and associated psychological symptoms are greater. “In my experience, PMDD symptoms can last the whole 2 weeks of the luteal phase, whereas PMS might occur a couple of days before menstruation,” said Ireland.

Symptoms include labile mood, nervousness, hopelessness, anger and aggressiveness, as well as tension and irritability. Those affected may have suicidal thoughts or even behaviors. In addition to a lethargic loss of interest in normal activities, patients with PMDD may feel paranoid, confused, exhausted, or out of control and experience insomnia or hypersomnia. They may have trouble concentrating or remembering. Some patients with PMDD may already be prone to attention-deficit/hyperactivity disorder and non–cycle-related depression, anxiety, and panic attacks.

Diagnosis is based on the presence of any five of the typical affective, somatic, or behavioral symptoms outlined above in the week before onset of menses.

“It’s important to do a careful diagnosis for PMDD and rule out other underlying conditions such as existing depressive or anxiety disorders,” said Haque. “Symptoms tend to be more intense in periods of high hormonal fluctuation such as in the postpartum and perimenopause periods. Women with PMDD should be monitored for postpartum depression.”

PMDD is considered both a gynecologic-genitourinary disorder and an affective condition.

In 2013, it was controversially included as a depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Strongly advocated by some patients, psychiatrists, and pharmaceutical companies, its inclusion was criticized by psychologists and generalists, who feared it would lead to overdiagnosis and pathologization of normal female hormonal changes. Women’s advocates protested that this inclusion would stigmatize female biology and harm their advance in society and the workplace, while some doctors continued to dismiss PMDD as not a serious concern.
 

Treatments

In its latest clinical practice guideline on PMDs, the American College of Obstetricians and Gynecologists (ACOG), for which Ireland served as the lead author, recommends that most patients with PMDD get medical treatment and outlines the following therapies, based on varying degrees of evidence strength.

Antidepressants. These may benefit patients with strong affective symptoms. Selective serotonin reuptake inhibitors such as sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), or fluoxetine (Prozac) are first choices.

Antidepressants may interrupt aberrant signaling in the HPGA, the circuit linking brain and ovaries and regulating the reproductive cycle. Serotonin norepinephrine reuptake inhibitor venlafaxine (Effexor) may also improve symptoms, but other types of antidepressants have not proven effective.

“The response to these well-tolerated drugs is rapid and can happen in the first 2 days,” said Ireland. The drugs may be taken either just in the luteal period or over the month, especially by patients with chronic depression or anxiety.

Hormonal therapy. ACOG recommends the use of combined oral contraceptives (COCs), gonadotropin-releasing hormone (GnRH) agonists to induce anovulation (with combined add-back hormones), progestin-only methods, and noncontraceptive continuous estrogen formulations. It notes, however, that COCs have not been more effective than placebo in reducing depressive symptom scores.

If symptoms do not improve over two to three cycles, an alternate therapy should be considered. Haque recommends an assessment after three cycles and then yearly.

Some women in her practice take both antidepressant and hormone therapy. “Unfortunately, there are no new pharmaceutical treatments on the horizon, but we have good ones already and we would love for patients to utilize them more often,” Ireland said.

Nonsteroidal anti-inflammatory drugs. Limited evidence shows these may reduce physical symptoms such as abdominal cramps, headaches, and general body aches, as well as some mood-related symptoms, which may be an indirect effect of pain alleviation.

Surgery. For women with the most severe intractable symptoms, bilateral oophorectomy with or without hysterectomy may be a last-resort option when medical management has failed. A trial period of GnRH agonist therapy (with or without adjunctive estrogen add-back treatment) is advised before surgery to predict a patient’s response to surgical management.

Acupuncture. ACOG suggests that acupuncture may help manage physical and affective premenstrual symptoms.

Diet. The usual dietary advice for premenstrual symptoms — such as consuming less caffeine, sugar, or alcohol and eating smaller, more frequent meals — is unlikely to help women with PMDD.

Exercise. Although it has not been well studied for PMDD, aerobic exercises such as walking, swimming, and biking tend to improve mood and energy levels in general. Exercise may reduce symptoms through several pathways, including effects on beta-endorphin, cortisol, and ovarian hormone levels.

Supplements. Vitamin B6, calcium and magnesium supplements, and herbal remedies are not supported by consistent or compelling evidence of efficacy. ACOG conditionally recommends calcium supplementation of 100-200 mg/d in adults to help manage physical and affective symptoms.

A small study suggested that supplemental zinc may improve both physical and psychological symptoms.

Cognitive-behavioral therapy. This treatment aims to interrupt negative and irrational thought patterns and may include awareness and education, as well as relaxation techniques, problem-solving and coping skills, and stress management. It has been associated with small to moderate improvement in anxiety and depression, said Ireland.

Peer support. Patients should consider joining a support group. The International Association for Premenstrual Disorders can help patients connect and develop coping skills.

The bottom line is that people with strong symptomatic evidence of PMDD should have medical intervention — to the benefit of their health and quality of life. Screening for PMDD should be part of women’s wellness examinations, said Ireland. “The impact of PMDD should not be minimized or dismissed,” said Haque. “And patients need to know there are very effective treatments.”

Ireland and Haque had no competing interests with regard to their comments.
 

A version of this article first appeared on Medscape.com.

Premenstrual disorders (PMDs), including premenstrual dysphoric disorder (PMDD), adversely affect the lives of millions of women worldwide. Most girls and women — as many as 80%-90%— will experience some premenstrual discomfort such as irritability, depressed mood, food or alcohol cravings, bloating, body aches, breast pain, constipation, or fatigue.

Diagnosable menstrual disorders include, collectively, premenstrual syndrome (PMS); PMDD, formerly called late luteal phase dysphoric disorder; and premenstrual worsening of another medical condition.

The most debilitating of these is PMDD, which has an estimated prevalence of about 4%-8% in women of reproductive age, according to obstetrician/gynecologist Hoosna Haque, MD, assistant professor of medicine at Columbia University Irving Medical Center in New York City.

“It’s difficult to be sure because this condition is underreported,” said Luu D. Ireland, MD, MPH, assistant professor of obstetrics and gynecology at UMass Memorial Medical Center in Worcester, Massachusetts. “But more women are coming forward, and there’s more discussion and media coverage of this condition.”

Occurring in the same post-follicular timeframe as PMS, PMDD takes cyclical discomfort to a more intense level, with a trifecta of affective comorbidities, somatic manifestations, and behavioral changes, all of which can seriously impair daily functioning, including work, physical activities, and personal relationships. Romantic and marital relationships can be particularly impaired.

Although recent cost figures are lacking, PMDs exact a considerable economic toll with increased direct healthcare costs from doctor visits and pharmaceuticals. A 2010 study found that US women with PMS were more likely to accrue in excess of $500 in healthcare visit costs over 2 years, and the figure would likely be higher today. PMDs also increase work/school absenteeism and reduce productivity.
 

Etiology

Brain areas that regulate emotion and behavior contain receptors for estrogen, progesterone, and other sex hormones, which affect the functioning of neurotransmitter systems influencing mood and thinking. Although the precise pathophysiology remains unclear, PMDD is likely multifactorial and results in a heightened sensitivity to normal fluctuations in estrogen and progesterone during the luteal phase of the menstrual cycle and dysfunction of the serotonin and gamma-aminobutyric acid neurotransmitter systems.

Patients with PMDD have lower levels of cortisol and beta-endorphins during both the follicular and luteal phases, suggesting abnormalities in the hypothalamic-pituitary-gonadal axis (HPGA), which is consistent with dysregulation in mood disorders.
 

Risk Factors

These include family history, past traumatic events, smoking, chronic pain syndrome, and obesity. There may be a genetic component as recent studies have suggested the involvement of the gene that codes for the serotonergic 5HT1A receptor and allelic variants of ESR1 in the development of PMS/PMDD.

A particularly concerning aspect of PMDs of any sort is their possible association with a higher risk for death from non-natural causes. In a recent Swedish study, which did not distinguish between PMDs in general and PMDD in particular, patients had an almost 60% greater risk for death from non-natural causes and nearly twice the risk for death by suicide compared with women without PMDs.

Those diagnosed with a PMD at an early age showed excess mortality, and the risk for suicide was elevated regardless of age. “These findings support the need for careful follow-up for young women with PMDs and the need for suicide prevention strategies,” wrote lead author Marion Opatowski, PhD, a medical epidemiologist at Karolinska Institutet in Stockholm, Sweden. “Women with severe PMDD should definitely be monitored for suicidal thoughts or behavior and they should have an emergency outreach plan in place,” Haque added.
 

Diagnosis

Although the somatic manifestations of PMDD resemble those of PMS, they are more severe and associated psychological symptoms are greater. “In my experience, PMDD symptoms can last the whole 2 weeks of the luteal phase, whereas PMS might occur a couple of days before menstruation,” said Ireland.

Symptoms include labile mood, nervousness, hopelessness, anger and aggressiveness, as well as tension and irritability. Those affected may have suicidal thoughts or even behaviors. In addition to a lethargic loss of interest in normal activities, patients with PMDD may feel paranoid, confused, exhausted, or out of control and experience insomnia or hypersomnia. They may have trouble concentrating or remembering. Some patients with PMDD may already be prone to attention-deficit/hyperactivity disorder and non–cycle-related depression, anxiety, and panic attacks.

Diagnosis is based on the presence of any five of the typical affective, somatic, or behavioral symptoms outlined above in the week before onset of menses.

“It’s important to do a careful diagnosis for PMDD and rule out other underlying conditions such as existing depressive or anxiety disorders,” said Haque. “Symptoms tend to be more intense in periods of high hormonal fluctuation such as in the postpartum and perimenopause periods. Women with PMDD should be monitored for postpartum depression.”

PMDD is considered both a gynecologic-genitourinary disorder and an affective condition.

In 2013, it was controversially included as a depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Strongly advocated by some patients, psychiatrists, and pharmaceutical companies, its inclusion was criticized by psychologists and generalists, who feared it would lead to overdiagnosis and pathologization of normal female hormonal changes. Women’s advocates protested that this inclusion would stigmatize female biology and harm their advance in society and the workplace, while some doctors continued to dismiss PMDD as not a serious concern.
 

Treatments

In its latest clinical practice guideline on PMDs, the American College of Obstetricians and Gynecologists (ACOG), for which Ireland served as the lead author, recommends that most patients with PMDD get medical treatment and outlines the following therapies, based on varying degrees of evidence strength.

Antidepressants. These may benefit patients with strong affective symptoms. Selective serotonin reuptake inhibitors such as sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), or fluoxetine (Prozac) are first choices.

Antidepressants may interrupt aberrant signaling in the HPGA, the circuit linking brain and ovaries and regulating the reproductive cycle. Serotonin norepinephrine reuptake inhibitor venlafaxine (Effexor) may also improve symptoms, but other types of antidepressants have not proven effective.

“The response to these well-tolerated drugs is rapid and can happen in the first 2 days,” said Ireland. The drugs may be taken either just in the luteal period or over the month, especially by patients with chronic depression or anxiety.

Hormonal therapy. ACOG recommends the use of combined oral contraceptives (COCs), gonadotropin-releasing hormone (GnRH) agonists to induce anovulation (with combined add-back hormones), progestin-only methods, and noncontraceptive continuous estrogen formulations. It notes, however, that COCs have not been more effective than placebo in reducing depressive symptom scores.

If symptoms do not improve over two to three cycles, an alternate therapy should be considered. Haque recommends an assessment after three cycles and then yearly.

Some women in her practice take both antidepressant and hormone therapy. “Unfortunately, there are no new pharmaceutical treatments on the horizon, but we have good ones already and we would love for patients to utilize them more often,” Ireland said.

Nonsteroidal anti-inflammatory drugs. Limited evidence shows these may reduce physical symptoms such as abdominal cramps, headaches, and general body aches, as well as some mood-related symptoms, which may be an indirect effect of pain alleviation.

Surgery. For women with the most severe intractable symptoms, bilateral oophorectomy with or without hysterectomy may be a last-resort option when medical management has failed. A trial period of GnRH agonist therapy (with or without adjunctive estrogen add-back treatment) is advised before surgery to predict a patient’s response to surgical management.

Acupuncture. ACOG suggests that acupuncture may help manage physical and affective premenstrual symptoms.

Diet. The usual dietary advice for premenstrual symptoms — such as consuming less caffeine, sugar, or alcohol and eating smaller, more frequent meals — is unlikely to help women with PMDD.

Exercise. Although it has not been well studied for PMDD, aerobic exercises such as walking, swimming, and biking tend to improve mood and energy levels in general. Exercise may reduce symptoms through several pathways, including effects on beta-endorphin, cortisol, and ovarian hormone levels.

Supplements. Vitamin B6, calcium and magnesium supplements, and herbal remedies are not supported by consistent or compelling evidence of efficacy. ACOG conditionally recommends calcium supplementation of 100-200 mg/d in adults to help manage physical and affective symptoms.

A small study suggested that supplemental zinc may improve both physical and psychological symptoms.

Cognitive-behavioral therapy. This treatment aims to interrupt negative and irrational thought patterns and may include awareness and education, as well as relaxation techniques, problem-solving and coping skills, and stress management. It has been associated with small to moderate improvement in anxiety and depression, said Ireland.

Peer support. Patients should consider joining a support group. The International Association for Premenstrual Disorders can help patients connect and develop coping skills.

The bottom line is that people with strong symptomatic evidence of PMDD should have medical intervention — to the benefit of their health and quality of life. Screening for PMDD should be part of women’s wellness examinations, said Ireland. “The impact of PMDD should not be minimized or dismissed,” said Haque. “And patients need to know there are very effective treatments.”

Ireland and Haque had no competing interests with regard to their comments.
 

A version of this article first appeared on Medscape.com.