OBG Management

Chronic pelvic pain (CPP) is defined as noncyclic pain in the pelvis, anterior abdominal wall, back, or buttocks that has been present for at least 6 months and is severe enough to cause functional disability or require medical care.¹ CPP is very common, with an estimated prevalence of 15% to 20%. It accounts for 20% of gynecology visits and 15% of hysterectomies in the United States, and it is believed to account for $2.8 billion in direct health care spending annually.^2–5

Caring for patients with CPP can be very challenging. They often arrive at your office frustrated, having seen multiple providers or having undergone multiple surgeries. They may come to you whether you are a general ObGyn or subspecialize in maternal-fetal medicine, oncology, reproductive endocrinology, urogynecology, or adolescent gynecology. From interactions with other providers or their own family members, these patients may have received the message—either subtly or overtly—that their pain is “all in their head.” As such, some patients may resist any implication that their pain does not have an anatomic source. It is therefore critical to have appropriate tools for evaluating and managing the complex problem of CPP.

Perform a thorough and thoughtful assessment

Chronic pelvic pain often presents as a constellation of symptoms with contributions from multiple sources, as opposed to a single disease entity. Occasionally there is a single cause of pain, such as a large endometrioma or degenerating fibroid, where surgery can be curative. But more commonly the pain arises from multiple organ systems. In such cases, surgery may be unnecessary and, often, can worsen pain.

Thoughtful evaluation is critical in the CPP population. Take a thorough patient history to determine the characteristics of pain (cyclic or constant, widespread or localized), exacerbating factors, sleep disturbances, fatigue, and current coping strategies. Focus a comprehensive physical examination on identifying the maneuvers that reproduce the patient’s pain, and include an examination of the pelvic floor muscles.⁶ In most cases, pelvic ultrasonography provides adequate evaluation for anatomic sources of pain.

Chronic pain does not behave like acute injury or postsurgical pain. Continuous peripheral pain signals for a prolonged period can lead to changes in how the brain processes pain; specifically, the brain can begin to amplify pain signals. This “central pain amplification” is characterized clinically by widespread pain, fatigue, sleep disturbances, memory difficulties, and somatic symptoms. Central pain amplification occurs in many chronic pain conditions, including fibromyalgia, interstitial cystitis, irritable bowel syndrome, low back pain, chronic headaches, and temporomandibular joint disorder.^7,8 Recent clinical and functional magnetic resonance imaging (MRI) studies demonstrate central pain amplification in many patients with CPP.^9–12 Notably, these findings are independent of the presence or severity of endometriosis.

In this article we discuss many therapies that have not been specifically studied in patients with CPP, and treatment efficacy is extrapolated from other conditions with chronic pain amplification, such as fibromyalgia or interstitial cystitis. Additionally, many treatments for conditions associated with central pain amplification are used off-label, that is, the US Food and Drug Administration (FDA) has not approved the medication for treatment of these specific conditions. This should be disclosed to patients during counseling.

Discuss treatment expectations with patients

Educating patients regarding the pathophysiology of chronic pain and setting reasonable expectations is the cornerstone of providing patient-centered care for this complex condition. We start most of our discussions about treatment options by telling patients that while we may not cure their pain, we will provide them with medical, surgical, and behavioral strategies that will reduce their pain, improve their function, and enhance their quality of life.

Surprisingly, most patients say that a cure is not their goal. They just want to feel better so they can return to work or activities, fully participate in family life, or not feel exhausted all the time. As such, a multimodal treatment plan is generally the best strategy for achieving a satisfactory improvement in symptoms.

Read about treating a case of continued pain after endometriosis treatment.

CASE 1 Patient’s pain continues after endometriosis excision

A 32-year-old woman (G1P1) reports having CPP for 8 years. She underwent excision of stage 1 endometriosis last year, which resulted in a modest improvement in pain for 6 months. Her pain is worse during menses, at the end of the day, and with vaginal intercourse (both during and lasting for 1 to 2 days after). On examination, you find diffuse pelvic floor tenderness but no adnexal masses or rectovaginal nodularity on palpation.

What treatment options would you consider for this patient?

Multimodal treatment often needed to manage CPP symptoms

The patient described in Case 1 may benefit from a combination of therapies that include analgesics, hormone suppression agents, and physical therapy (PT) (TABLE).

Analgesics

Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen and naproxen, work by inhibiting cyclooxygenase enzyme, which decreases assembly of peripheral prostaglandins and thromboxane. In a large Cochrane review, NSAIDs were associated with moderate or excellent pain relief for approximately 50% of patients with dysmenorrhea, and they have been shown to reduce menstrual flow due to decreased production of uterine prostaglandins.¹³ There is little evidence for use of NSAIDs in chronic pain conditions.

Acetaminophen’s mechanism of action is unclear, but the drug likely inhibits central prostaglandin synthesis, and it works synergistically with other analgesics.

Opioids act on μ and δ opioid receptors in the central and peripheral nervous systems as well as in the gastrointestinal system. No evidence supports opioid use in CPP or other chronic pain conditions. Long-term opioid use is associated with a multitude of adverse effects, risk for dependence, and the induction of opioid-induced hyperalgesia (in which patients develop greater sensitivity to pain stimuli).

Analgesics, specifically NSAIDs, can be considered for use in patients with dysmenorrhea, cyclic pain exacerbation, or a suspected inflammatory component of pain. Best practices include scheduling NSAID use before the onset of menses and continuing the drugs on a scheduled basis throughout. NSAIDs should be used for a brief period, and regular use on an empty stomach should be avoided.

Hormone suppression

Many types of hormone suppression therapy are available, including combined estrogen-progestin medications, progestin-only medications, and gonadotropin-releasing hormone (GnRH) agonists and antagonists.

Combined estrogen-progestin medications include oral contraceptive pills (OCPs), vaginal rings, and transdermal patches. Combined estrogen-progestin methods cause atrophy of eutopic and ectopic endometrium and suppress GnRH.

Progestin-only methods include oral formulations, the levonorgestrel intrauterine device, intramuscular and subcuticular injections, and subdermal implants. Progestin-only methods lead to atrophy of eutopic and ectopic endometrium.

A GnRH agonist, leuprolide depot works by downregulating luteinizing hormone and follicle stimulating hormone release from the pituitary, causing suppression of ovarian follicular development and ovulation, leading to a hypoestrogenic state.

Combined estrogen-progestin formulations and progestin-only options are often considered first-line therapy for dysmenorrhea and endometriosis.¹³ Continuous administration, with the goal of inducing amenorrhea, is effective in the treatment of dysmenorrhea. Several randomized controlled trials have shown that different types of hormone suppression agents are, essentially, equally effective.^13–15 Treatment recommendations therefore should focus on adverse effects, cost, and patient preference. GnRH agonists and norethindrone are not FDA approved for the treatment of endometriosis.

It may be appropriate to consider use of hormone suppression therapy in patients with menstrual exacerbation of pain symptoms, including those with a history of endometriosis. We generally advise patients that the goal is amenorrhea and that achieving it often involves a process of trying different formulations to find the best fit. Remember that GnRH agonists are dependent on a functional hypothalamic-pituitary-ovarian axis, and they are unlikely to be effective in women with suspected residual endometriosis who have had a bilateral oophorectomy.

Physical therapy

For CPP, PT typically targets musculoskeletal dysfunction in the pelvic floor, abdominal wall, hips, and back. Interventions include muscle control, mobilization, and biofeedback. Pelvic PT has been shown to improve pain and dyspareunia in patients with CPP, coccydynia, and vestibulodynia.^16–18 One large study found a significant, patient-directed decrease in pain medication use after pelvic floor PT.¹⁹ Pelvic PT for patients with interstitial cystitis and pelvic floor tenderness resulted in improved pain and bladder symptoms.²⁰

Pelvic PT can be considered for patients with pain reproducible with palpation of the pelvic floor, abdominal wall, paraspinal-lumbar muscles, or sacroiliac joints. Best practices include referral to a therapist who has specialized training in CPP, including pelvic floor therapy. It is important to clearly list the indication for referral, as many of these therapists also treat stress urinary incontinence. The wrong exercises can result in increased hypercontractility of pelvic floor muscles, which can worsen pelvic pain.

It is also critical to clarify expectations with your patient at the time of PT referral. Specifically, advise patients that when beginning therapy, it is common to experience a temporary increase in discomfort of the pelvic muscles. Inform patients also to expect that their therapist will perform internal manipulation of the pelvic floor muscles through the vagina, as this can be surprising for some patients. Finally, counsel patients that their adherence to daily home exercises improves their chance of a durable, long-term successful response.²¹

CASE 1 Treatment recommendations

For treatment of this patient’s CPP, consider scheduled naproxen therapy during menses, continuous OCPs, and referral for pelvic floor PT.

Read about treating a case of pain, sleep disturbance, and depression.

CASE 2 Patient with long-standing CPP, multiple diagnoses, and sleep problems

A 30-year-old woman (G2P2) reports having had CPP for 17 years. She is amenorrheic with continuous OCP treatment. She had experienced some improvement with pelvic PT. The patient reports that she has daily pain with intermittent pain flares and that she is exhausted and has poor sleep quality, which she attributes to pain. She has been diagnosed with interstitial cystitis, irritable bowel syndrome, and temporomandibular joint disorder. She has a history of depression, which she feels is well controlled with bupropion. Physical examination reveals that the patient has diffuse but mild pain in the pelvic floor and abdominal wall muscles.

What further pain management options can you offer for this patient?

Managing pain, sleep disturbance, and depression

This patient has been living with CPP for many years, and she has sleep difficulties that might be exacerbating pain or result from pain (or both). She is already on continuous OCPs and has had some relief with pelvic PT. Other options that may help with her multiple issues include antidepressants, cyclobenzaprine, and calcium channel blockers.

Antidepressants

Several classes of antidepressants have been used in the treatment of chronic pain conditions, specifically, tricyclic antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Commonly used TCAs include amitriptyline, nortriptyline, desipramine, and doxepin. Commonly used SNRIs are duloxetine and milnacipran. Both TCAs and SNRIs increase the availability of norepinephrine and serotonin, which are thought to act on the descending pain inhibitory systems to decrease pain sensitivity. Of note, most selective serotonin reuptake inhibitors (SSRIs) at typical doses do not exert a significant enough impact on norepinephrine to be useful for chronic pain.²²

Evidence is limited on the use of antidepressants for treating CPP. Amitriptyline is the most extensively studied antidepressant. Amitriptyline treatment resulted in modest pain improvement in patients with CPP and fibromyalgia.^23,24 Bothersome anticholinergic effects, including fatigue, dry mouth, and constipation, often are reported with TCAs. Adverse effects tend to be less with nortriptyline or desipramine compared with amitriptyline, but possibly at the expense of efficacy.

While SNRIs have not yet been studied in CPP, several investigations have shown that they improve pain and quality of life in fibromyalgia patients.^22,25

Antidepressant therapy may be appropriate for patients with suspected central pain amplification, widespread pain, and sleep disturbances. Best practices include patient education and careful discussion of this option with your patient. We suggest that clinicians explain that antidepressant medications alter the function of neurotransmitters, which modulate pain signals. While neurotransmitters also are involved in mood modulation, this is not the therapeutic goal in this circumstance. In addition, the doses used for the effective treatment of chronic pain are significantly lower than those needed to treat depression effectively.

Patients often need to hear that you believe that their pain is real and is not a manifestation of depression or another mood disorder. If you suspect that the patient also has untreated depression, address this as its own issue and use medications that have greater efficacy for mood symptoms.

Because many antidepressants can cause sedation, they are best taken before bedtime. Also, slow dose titration over several weeks will reduce the chance of bothersome adverse effects. Counsel patients that efficacy is not generally seen until at goal dose for several weeks. Be aware of interactions with other medications that can cause serotonin syndrome.

Cyclobenzaprine

Cyclobenzaprine is a muscle relaxant that also has activity in the central nervous system. The drug’s precise mechanism of action is not known, but it appears to potentiate norepinephrine and bind to serotonin receptors. Thus, it also likely has some TCA-like activity.

Cyclobenzaprine has not been studied in patients with CPP. In fibromyalgia patients, however, it produced significant improvements in pain, sleep, fatigue, and tenderness.^26,27 In our anecdotal experience with CPP patients, cyclobenzaprine has been one of the most impactful therapies. It hits the “chronic pain triad,” meaning that it helps with myofascial pain, neuropathic pain, and sleep disturbances.

Cyclobenzaprine treatment may be considered for patients with myofascial pain, sleep disturbances, and clinical symptoms of central pain amplification. Best practices include starting with low (5 mg) scheduled doses at bedtime and slowly titrating the dose. Drowsiness is a very common side effect, so we try to use that to the patient’s advantage to help with sleep quality.

Notably, sleep disturbances are highly prevalent in patients with chronic pain.²⁸ The relationship appears to be bidirectional, meaning that chronic pain negatively impacts sleep quality, and poor sleep quality causes amplified perception of pain.^28–30 Interventions that improve sleep quality have been associated with improvements in pain, coping, mood, and functional status.³¹ Helping a patient to improve her sleep generally requires a multifaceted approach. It always involves “sleep hygiene” or a behavioral component, and pharmacologic assistance may be considered when improved sleep hygiene does not provide adequately improved sleep quality.

Calcium channel blockers

Gabapentin and pregabalin are calcium channel blockers that inhibit the reuptake of glutamate, norepinephrine, and substance P, which helps to decrease pain sensitivity. They also act as membrane stabilizers, reducing hyperexcitability of peripheral and central nerves. Studies have shown that in patients with CPP, gabapentin resulted in improved pain and mood symptoms with few adverse effects.^23,32 Patients with fibromyalgia had improvements in pain, sleep, quality of life, fatigue, and anxiety with both gabapentin and pregabalin.³³

It is appropriate to consider use of gabapentin or pregabalin in patients with central pain amplification and sleep disturbances. Best practices include starting with a low dose at bedtime. Traditionally, gabapentin is given in 3 equal doses throughout the day. In our experience, patients report less daytime drowsiness and better sleep quality if two-thirds of the daily dose is given at night, with the remaining daily dose broken up into 2 smaller daytime doses. Slow titration over several weeks will reduce risk of bothersome adverse effects. Patients should be counseled that efficacy is not generally seen until treatment is at goal dose for several weeks.

CASE 2 Treatment recommendations

For this patient with daily pelvic pain, multiple diagnoses that have a pain component, and poor sleep quality, consider a treatment plan that includes scheduled cyclobenzaprine, improved sleep hygiene, and, if needed, gabapentin.

Read about treating a case of focal pain.

CASE 3 Cesarean delivery, hysterectomy, and continued pelvic pain

A 38-year-old woman (G2P2) has had CPP for the past 10 years. She developed persistent left lower-quadrant pain after cesarean delivery of her son. She had a hysterectomy 2 years ago for CPP, after which her pain worsened. She describes daily pain with intermittent flares. On examination, the patient has focal left lower-quadrant pain lateral to the left apex of her Pfannenstiel incision.

What treatment approach would be appropriate for this patient?

Focal pain requires a precisely targeted treatment

This patient with focal left lower-quadrant pain is a candidate for anesthetic trigger point injections in the affected area near her Pfannenstiel incision.

Anesthetic injections

Consider the presence of trigger points and peripheral neuropathy in patients with focal abdominal wall pain. Trigger points are focal, palpable nodules within muscles. They are markedly painful to palpation and are associated with referred pain, motor dysfunction, and occasionally autonomic symptoms. They frequently are seen in abdominal wall or pelvic floor muscles in patients with CPP and are caused by abnormal neuromuscular depolarization.

The ilioinguinal, iliohypogastric, and genitofemoral nerves are in close proximity to Pfannenstiel and laparoscopic port site incisions. These nerves may be injured directly during surgery, but they also may be compressed by postoperative scarring.

Anesthetics, such as lidocaine and bupivacaine, which act as sodium channel blockers, can be injected into this area, and improvement often substantially outlasts the anesthetic’s duration of action. While these drugs’ mechanism of action is not clear, theories include altered function of sodium channels on sensory nerves with repeated anesthetic exposure, dry needling that occurs during injection, hydrodissection of tight connective tissue bands surrounding neuromuscular bundles, or depletion of substance P and neuropeptides as a result of injection.^34,35

In several studies, patients with CPP reported decreased pain with lidocaine injections in pelvic floor or abdominal wall trigger points.^36–38 Patients with fibromyalgia reported improvement in pain and a decreased need for NSAIDs with bupivacaine trigger point injections.³⁹ While abdominal wall nerve blocks have not been extensively studied in patients with chronic neuropathic pain following gynecologic surgery, they have been shown to substantially improve chronic neuropathic pain following inguinal hernia repair.⁴⁰

Anesthetic injections appropriately may be considered in patients with focal pain in a muscle or in the distribution of abdominal wall nerves, palpation of which reproduces pain symptoms. Patients with diffuse pain are less likely to benefit from anesthetic injections. Best practices include careful examination with attention to areas of prior abdominal incisions.

Our practice is to inject each affected area with a mix of 9 mL of 1% lidocaine and 1 mL of sodium bicarbonate. If a patient reports at least 24 hours of improvement, we repeat the injection in 2 to 4 weeks. The goal is for the patient to experience a progressively longer duration of benefit with subsequent injections. We perform repeat injections shortly after pain begins to recur at that site. The patient should eventually graduate from receiving regular injections and may return for a remedial injection if pain recurs.

CASE 3 Treatment recommendations

For this patient with persistent focal left-lower quadrant pain and a defined trigger point near her Pfannenstiel incision, consider anesthetic injection in the left lower quadrant.

Work toward realistic symptom improvement

Remember that living with chronic pain is exhausting, and empathy with a patient-centered approach is the most important ingredient for patient improvement and satisfaction. Discuss realistic expectations with patients. Remind them that there is no magic bullet for the complex problem of CPP, and that chronic conditions generally do not improve overnight. Focus on improving the patient’s function and quality of life, and applaud symptom improvement rather than focusing on complete pain resolution.

As these visits often require a good deal of patient education, budget more appointment time if feasible. We find that scheduling frequent return visits (approximately every 3 to 4 months) allows timely treatment follow-up so that changes may be made if needed. If you have maximized your available treatment options, referring the patient to a specialist with additional training in CPP is a sensible next step.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Chronic pelvic pain (CPP) is defined as noncyclic pain in the pelvis, anterior abdominal wall, back, or buttocks that has been present for at least 6 months and is severe enough to cause functional disability or require medical care.¹ CPP is very common, with an estimated prevalence of 15% to 20%. It accounts for 20% of gynecology visits and 15% of hysterectomies in the United States, and it is believed to account for $2.8 billion in direct health care spending annually.^2–5

Caring for patients with CPP can be very challenging. They often arrive at your office frustrated, having seen multiple providers or having undergone multiple surgeries. They may come to you whether you are a general ObGyn or subspecialize in maternal-fetal medicine, oncology, reproductive endocrinology, urogynecology, or adolescent gynecology. From interactions with other providers or their own family members, these patients may have received the message—either subtly or overtly—that their pain is “all in their head.” As such, some patients may resist any implication that their pain does not have an anatomic source. It is therefore critical to have appropriate tools for evaluating and managing the complex problem of CPP.

Perform a thorough and thoughtful assessment

Chronic pelvic pain often presents as a constellation of symptoms with contributions from multiple sources, as opposed to a single disease entity. Occasionally there is a single cause of pain, such as a large endometrioma or degenerating fibroid, where surgery can be curative. But more commonly the pain arises from multiple organ systems. In such cases, surgery may be unnecessary and, often, can worsen pain.

Thoughtful evaluation is critical in the CPP population. Take a thorough patient history to determine the characteristics of pain (cyclic or constant, widespread or localized), exacerbating factors, sleep disturbances, fatigue, and current coping strategies. Focus a comprehensive physical examination on identifying the maneuvers that reproduce the patient’s pain, and include an examination of the pelvic floor muscles.⁶ In most cases, pelvic ultrasonography provides adequate evaluation for anatomic sources of pain.

Chronic pain does not behave like acute injury or postsurgical pain. Continuous peripheral pain signals for a prolonged period can lead to changes in how the brain processes pain; specifically, the brain can begin to amplify pain signals. This “central pain amplification” is characterized clinically by widespread pain, fatigue, sleep disturbances, memory difficulties, and somatic symptoms. Central pain amplification occurs in many chronic pain conditions, including fibromyalgia, interstitial cystitis, irritable bowel syndrome, low back pain, chronic headaches, and temporomandibular joint disorder.^7,8 Recent clinical and functional magnetic resonance imaging (MRI) studies demonstrate central pain amplification in many patients with CPP.^9–12 Notably, these findings are independent of the presence or severity of endometriosis.

In this article we discuss many therapies that have not been specifically studied in patients with CPP, and treatment efficacy is extrapolated from other conditions with chronic pain amplification, such as fibromyalgia or interstitial cystitis. Additionally, many treatments for conditions associated with central pain amplification are used off-label, that is, the US Food and Drug Administration (FDA) has not approved the medication for treatment of these specific conditions. This should be disclosed to patients during counseling.

Discuss treatment expectations with patients

Educating patients regarding the pathophysiology of chronic pain and setting reasonable expectations is the cornerstone of providing patient-centered care for this complex condition. We start most of our discussions about treatment options by telling patients that while we may not cure their pain, we will provide them with medical, surgical, and behavioral strategies that will reduce their pain, improve their function, and enhance their quality of life.

Surprisingly, most patients say that a cure is not their goal. They just want to feel better so they can return to work or activities, fully participate in family life, or not feel exhausted all the time. As such, a multimodal treatment plan is generally the best strategy for achieving a satisfactory improvement in symptoms.

Read about treating a case of continued pain after endometriosis treatment.

CASE 1 Patient’s pain continues after endometriosis excision

A 32-year-old woman (G1P1) reports having CPP for 8 years. She underwent excision of stage 1 endometriosis last year, which resulted in a modest improvement in pain for 6 months. Her pain is worse during menses, at the end of the day, and with vaginal intercourse (both during and lasting for 1 to 2 days after). On examination, you find diffuse pelvic floor tenderness but no adnexal masses or rectovaginal nodularity on palpation.

What treatment options would you consider for this patient?

Multimodal treatment often needed to manage CPP symptoms

The patient described in Case 1 may benefit from a combination of therapies that include analgesics, hormone suppression agents, and physical therapy (PT) (TABLE).

Analgesics

Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen and naproxen, work by inhibiting cyclooxygenase enzyme, which decreases assembly of peripheral prostaglandins and thromboxane. In a large Cochrane review, NSAIDs were associated with moderate or excellent pain relief for approximately 50% of patients with dysmenorrhea, and they have been shown to reduce menstrual flow due to decreased production of uterine prostaglandins.¹³ There is little evidence for use of NSAIDs in chronic pain conditions.

Acetaminophen’s mechanism of action is unclear, but the drug likely inhibits central prostaglandin synthesis, and it works synergistically with other analgesics.

Opioids act on μ and δ opioid receptors in the central and peripheral nervous systems as well as in the gastrointestinal system. No evidence supports opioid use in CPP or other chronic pain conditions. Long-term opioid use is associated with a multitude of adverse effects, risk for dependence, and the induction of opioid-induced hyperalgesia (in which patients develop greater sensitivity to pain stimuli).

Analgesics, specifically NSAIDs, can be considered for use in patients with dysmenorrhea, cyclic pain exacerbation, or a suspected inflammatory component of pain. Best practices include scheduling NSAID use before the onset of menses and continuing the drugs on a scheduled basis throughout. NSAIDs should be used for a brief period, and regular use on an empty stomach should be avoided.

Hormone suppression

Many types of hormone suppression therapy are available, including combined estrogen-progestin medications, progestin-only medications, and gonadotropin-releasing hormone (GnRH) agonists and antagonists.

Combined estrogen-progestin medications include oral contraceptive pills (OCPs), vaginal rings, and transdermal patches. Combined estrogen-progestin methods cause atrophy of eutopic and ectopic endometrium and suppress GnRH.

Progestin-only methods include oral formulations, the levonorgestrel intrauterine device, intramuscular and subcuticular injections, and subdermal implants. Progestin-only methods lead to atrophy of eutopic and ectopic endometrium.

A GnRH agonist, leuprolide depot works by downregulating luteinizing hormone and follicle stimulating hormone release from the pituitary, causing suppression of ovarian follicular development and ovulation, leading to a hypoestrogenic state.

Combined estrogen-progestin formulations and progestin-only options are often considered first-line therapy for dysmenorrhea and endometriosis.¹³ Continuous administration, with the goal of inducing amenorrhea, is effective in the treatment of dysmenorrhea. Several randomized controlled trials have shown that different types of hormone suppression agents are, essentially, equally effective.^13–15 Treatment recommendations therefore should focus on adverse effects, cost, and patient preference. GnRH agonists and norethindrone are not FDA approved for the treatment of endometriosis.

It may be appropriate to consider use of hormone suppression therapy in patients with menstrual exacerbation of pain symptoms, including those with a history of endometriosis. We generally advise patients that the goal is amenorrhea and that achieving it often involves a process of trying different formulations to find the best fit. Remember that GnRH agonists are dependent on a functional hypothalamic-pituitary-ovarian axis, and they are unlikely to be effective in women with suspected residual endometriosis who have had a bilateral oophorectomy.

Physical therapy

For CPP, PT typically targets musculoskeletal dysfunction in the pelvic floor, abdominal wall, hips, and back. Interventions include muscle control, mobilization, and biofeedback. Pelvic PT has been shown to improve pain and dyspareunia in patients with CPP, coccydynia, and vestibulodynia.^16–18 One large study found a significant, patient-directed decrease in pain medication use after pelvic floor PT.¹⁹ Pelvic PT for patients with interstitial cystitis and pelvic floor tenderness resulted in improved pain and bladder symptoms.²⁰

Pelvic PT can be considered for patients with pain reproducible with palpation of the pelvic floor, abdominal wall, paraspinal-lumbar muscles, or sacroiliac joints. Best practices include referral to a therapist who has specialized training in CPP, including pelvic floor therapy. It is important to clearly list the indication for referral, as many of these therapists also treat stress urinary incontinence. The wrong exercises can result in increased hypercontractility of pelvic floor muscles, which can worsen pelvic pain.

It is also critical to clarify expectations with your patient at the time of PT referral. Specifically, advise patients that when beginning therapy, it is common to experience a temporary increase in discomfort of the pelvic muscles. Inform patients also to expect that their therapist will perform internal manipulation of the pelvic floor muscles through the vagina, as this can be surprising for some patients. Finally, counsel patients that their adherence to daily home exercises improves their chance of a durable, long-term successful response.²¹

CASE 1 Treatment recommendations

For treatment of this patient’s CPP, consider scheduled naproxen therapy during menses, continuous OCPs, and referral for pelvic floor PT.

Read about treating a case of pain, sleep disturbance, and depression.

CASE 2 Patient with long-standing CPP, multiple diagnoses, and sleep problems

A 30-year-old woman (G2P2) reports having had CPP for 17 years. She is amenorrheic with continuous OCP treatment. She had experienced some improvement with pelvic PT. The patient reports that she has daily pain with intermittent pain flares and that she is exhausted and has poor sleep quality, which she attributes to pain. She has been diagnosed with interstitial cystitis, irritable bowel syndrome, and temporomandibular joint disorder. She has a history of depression, which she feels is well controlled with bupropion. Physical examination reveals that the patient has diffuse but mild pain in the pelvic floor and abdominal wall muscles.

What further pain management options can you offer for this patient?

Managing pain, sleep disturbance, and depression

This patient has been living with CPP for many years, and she has sleep difficulties that might be exacerbating pain or result from pain (or both). She is already on continuous OCPs and has had some relief with pelvic PT. Other options that may help with her multiple issues include antidepressants, cyclobenzaprine, and calcium channel blockers.

Antidepressants

Several classes of antidepressants have been used in the treatment of chronic pain conditions, specifically, tricyclic antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Commonly used TCAs include amitriptyline, nortriptyline, desipramine, and doxepin. Commonly used SNRIs are duloxetine and milnacipran. Both TCAs and SNRIs increase the availability of norepinephrine and serotonin, which are thought to act on the descending pain inhibitory systems to decrease pain sensitivity. Of note, most selective serotonin reuptake inhibitors (SSRIs) at typical doses do not exert a significant enough impact on norepinephrine to be useful for chronic pain.²²

Evidence is limited on the use of antidepressants for treating CPP. Amitriptyline is the most extensively studied antidepressant. Amitriptyline treatment resulted in modest pain improvement in patients with CPP and fibromyalgia.^23,24 Bothersome anticholinergic effects, including fatigue, dry mouth, and constipation, often are reported with TCAs. Adverse effects tend to be less with nortriptyline or desipramine compared with amitriptyline, but possibly at the expense of efficacy.

While SNRIs have not yet been studied in CPP, several investigations have shown that they improve pain and quality of life in fibromyalgia patients.^22,25

Antidepressant therapy may be appropriate for patients with suspected central pain amplification, widespread pain, and sleep disturbances. Best practices include patient education and careful discussion of this option with your patient. We suggest that clinicians explain that antidepressant medications alter the function of neurotransmitters, which modulate pain signals. While neurotransmitters also are involved in mood modulation, this is not the therapeutic goal in this circumstance. In addition, the doses used for the effective treatment of chronic pain are significantly lower than those needed to treat depression effectively.

Patients often need to hear that you believe that their pain is real and is not a manifestation of depression or another mood disorder. If you suspect that the patient also has untreated depression, address this as its own issue and use medications that have greater efficacy for mood symptoms.

Because many antidepressants can cause sedation, they are best taken before bedtime. Also, slow dose titration over several weeks will reduce the chance of bothersome adverse effects. Counsel patients that efficacy is not generally seen until at goal dose for several weeks. Be aware of interactions with other medications that can cause serotonin syndrome.

Cyclobenzaprine

Cyclobenzaprine is a muscle relaxant that also has activity in the central nervous system. The drug’s precise mechanism of action is not known, but it appears to potentiate norepinephrine and bind to serotonin receptors. Thus, it also likely has some TCA-like activity.

Cyclobenzaprine has not been studied in patients with CPP. In fibromyalgia patients, however, it produced significant improvements in pain, sleep, fatigue, and tenderness.^26,27 In our anecdotal experience with CPP patients, cyclobenzaprine has been one of the most impactful therapies. It hits the “chronic pain triad,” meaning that it helps with myofascial pain, neuropathic pain, and sleep disturbances.

Cyclobenzaprine treatment may be considered for patients with myofascial pain, sleep disturbances, and clinical symptoms of central pain amplification. Best practices include starting with low (5 mg) scheduled doses at bedtime and slowly titrating the dose. Drowsiness is a very common side effect, so we try to use that to the patient’s advantage to help with sleep quality.

Notably, sleep disturbances are highly prevalent in patients with chronic pain.²⁸ The relationship appears to be bidirectional, meaning that chronic pain negatively impacts sleep quality, and poor sleep quality causes amplified perception of pain.^28–30 Interventions that improve sleep quality have been associated with improvements in pain, coping, mood, and functional status.³¹ Helping a patient to improve her sleep generally requires a multifaceted approach. It always involves “sleep hygiene” or a behavioral component, and pharmacologic assistance may be considered when improved sleep hygiene does not provide adequately improved sleep quality.

Calcium channel blockers

Gabapentin and pregabalin are calcium channel blockers that inhibit the reuptake of glutamate, norepinephrine, and substance P, which helps to decrease pain sensitivity. They also act as membrane stabilizers, reducing hyperexcitability of peripheral and central nerves. Studies have shown that in patients with CPP, gabapentin resulted in improved pain and mood symptoms with few adverse effects.^23,32 Patients with fibromyalgia had improvements in pain, sleep, quality of life, fatigue, and anxiety with both gabapentin and pregabalin.³³

It is appropriate to consider use of gabapentin or pregabalin in patients with central pain amplification and sleep disturbances. Best practices include starting with a low dose at bedtime. Traditionally, gabapentin is given in 3 equal doses throughout the day. In our experience, patients report less daytime drowsiness and better sleep quality if two-thirds of the daily dose is given at night, with the remaining daily dose broken up into 2 smaller daytime doses. Slow titration over several weeks will reduce risk of bothersome adverse effects. Patients should be counseled that efficacy is not generally seen until treatment is at goal dose for several weeks.

CASE 2 Treatment recommendations

For this patient with daily pelvic pain, multiple diagnoses that have a pain component, and poor sleep quality, consider a treatment plan that includes scheduled cyclobenzaprine, improved sleep hygiene, and, if needed, gabapentin.

Read about treating a case of focal pain.

CASE 3 Cesarean delivery, hysterectomy, and continued pelvic pain

A 38-year-old woman (G2P2) has had CPP for the past 10 years. She developed persistent left lower-quadrant pain after cesarean delivery of her son. She had a hysterectomy 2 years ago for CPP, after which her pain worsened. She describes daily pain with intermittent flares. On examination, the patient has focal left lower-quadrant pain lateral to the left apex of her Pfannenstiel incision.

What treatment approach would be appropriate for this patient?

Focal pain requires a precisely targeted treatment

This patient with focal left lower-quadrant pain is a candidate for anesthetic trigger point injections in the affected area near her Pfannenstiel incision.

Anesthetic injections

Consider the presence of trigger points and peripheral neuropathy in patients with focal abdominal wall pain. Trigger points are focal, palpable nodules within muscles. They are markedly painful to palpation and are associated with referred pain, motor dysfunction, and occasionally autonomic symptoms. They frequently are seen in abdominal wall or pelvic floor muscles in patients with CPP and are caused by abnormal neuromuscular depolarization.

The ilioinguinal, iliohypogastric, and genitofemoral nerves are in close proximity to Pfannenstiel and laparoscopic port site incisions. These nerves may be injured directly during surgery, but they also may be compressed by postoperative scarring.

Anesthetics, such as lidocaine and bupivacaine, which act as sodium channel blockers, can be injected into this area, and improvement often substantially outlasts the anesthetic’s duration of action. While these drugs’ mechanism of action is not clear, theories include altered function of sodium channels on sensory nerves with repeated anesthetic exposure, dry needling that occurs during injection, hydrodissection of tight connective tissue bands surrounding neuromuscular bundles, or depletion of substance P and neuropeptides as a result of injection.^34,35

In several studies, patients with CPP reported decreased pain with lidocaine injections in pelvic floor or abdominal wall trigger points.^36–38 Patients with fibromyalgia reported improvement in pain and a decreased need for NSAIDs with bupivacaine trigger point injections.³⁹ While abdominal wall nerve blocks have not been extensively studied in patients with chronic neuropathic pain following gynecologic surgery, they have been shown to substantially improve chronic neuropathic pain following inguinal hernia repair.⁴⁰

Anesthetic injections appropriately may be considered in patients with focal pain in a muscle or in the distribution of abdominal wall nerves, palpation of which reproduces pain symptoms. Patients with diffuse pain are less likely to benefit from anesthetic injections. Best practices include careful examination with attention to areas of prior abdominal incisions.

Our practice is to inject each affected area with a mix of 9 mL of 1% lidocaine and 1 mL of sodium bicarbonate. If a patient reports at least 24 hours of improvement, we repeat the injection in 2 to 4 weeks. The goal is for the patient to experience a progressively longer duration of benefit with subsequent injections. We perform repeat injections shortly after pain begins to recur at that site. The patient should eventually graduate from receiving regular injections and may return for a remedial injection if pain recurs.

CASE 3 Treatment recommendations

For this patient with persistent focal left-lower quadrant pain and a defined trigger point near her Pfannenstiel incision, consider anesthetic injection in the left lower quadrant.

Work toward realistic symptom improvement

Remember that living with chronic pain is exhausting, and empathy with a patient-centered approach is the most important ingredient for patient improvement and satisfaction. Discuss realistic expectations with patients. Remind them that there is no magic bullet for the complex problem of CPP, and that chronic conditions generally do not improve overnight. Focus on improving the patient’s function and quality of life, and applaud symptom improvement rather than focusing on complete pain resolution.

As these visits often require a good deal of patient education, budget more appointment time if feasible. We find that scheduling frequent return visits (approximately every 3 to 4 months) allows timely treatment follow-up so that changes may be made if needed. If you have maximized your available treatment options, referring the patient to a specialist with additional training in CPP is a sensible next step.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Chronic pelvic pain (CPP) is defined as noncyclic pain in the pelvis, anterior abdominal wall, back, or buttocks that has been present for at least 6 months and is severe enough to cause functional disability or require medical care.¹ CPP is very common, with an estimated prevalence of 15% to 20%. It accounts for 20% of gynecology visits and 15% of hysterectomies in the United States, and it is believed to account for $2.8 billion in direct health care spending annually.^2–5

Caring for patients with CPP can be very challenging. They often arrive at your office frustrated, having seen multiple providers or having undergone multiple surgeries. They may come to you whether you are a general ObGyn or subspecialize in maternal-fetal medicine, oncology, reproductive endocrinology, urogynecology, or adolescent gynecology. From interactions with other providers or their own family members, these patients may have received the message—either subtly or overtly—that their pain is “all in their head.” As such, some patients may resist any implication that their pain does not have an anatomic source. It is therefore critical to have appropriate tools for evaluating and managing the complex problem of CPP.

Perform a thorough and thoughtful assessment

Chronic pelvic pain often presents as a constellation of symptoms with contributions from multiple sources, as opposed to a single disease entity. Occasionally there is a single cause of pain, such as a large endometrioma or degenerating fibroid, where surgery can be curative. But more commonly the pain arises from multiple organ systems. In such cases, surgery may be unnecessary and, often, can worsen pain.

Thoughtful evaluation is critical in the CPP population. Take a thorough patient history to determine the characteristics of pain (cyclic or constant, widespread or localized), exacerbating factors, sleep disturbances, fatigue, and current coping strategies. Focus a comprehensive physical examination on identifying the maneuvers that reproduce the patient’s pain, and include an examination of the pelvic floor muscles.⁶ In most cases, pelvic ultrasonography provides adequate evaluation for anatomic sources of pain.

Chronic pain does not behave like acute injury or postsurgical pain. Continuous peripheral pain signals for a prolonged period can lead to changes in how the brain processes pain; specifically, the brain can begin to amplify pain signals. This “central pain amplification” is characterized clinically by widespread pain, fatigue, sleep disturbances, memory difficulties, and somatic symptoms. Central pain amplification occurs in many chronic pain conditions, including fibromyalgia, interstitial cystitis, irritable bowel syndrome, low back pain, chronic headaches, and temporomandibular joint disorder.^7,8 Recent clinical and functional magnetic resonance imaging (MRI) studies demonstrate central pain amplification in many patients with CPP.^9–12 Notably, these findings are independent of the presence or severity of endometriosis.

In this article we discuss many therapies that have not been specifically studied in patients with CPP, and treatment efficacy is extrapolated from other conditions with chronic pain amplification, such as fibromyalgia or interstitial cystitis. Additionally, many treatments for conditions associated with central pain amplification are used off-label, that is, the US Food and Drug Administration (FDA) has not approved the medication for treatment of these specific conditions. This should be disclosed to patients during counseling.

Discuss treatment expectations with patients

Educating patients regarding the pathophysiology of chronic pain and setting reasonable expectations is the cornerstone of providing patient-centered care for this complex condition. We start most of our discussions about treatment options by telling patients that while we may not cure their pain, we will provide them with medical, surgical, and behavioral strategies that will reduce their pain, improve their function, and enhance their quality of life.

Surprisingly, most patients say that a cure is not their goal. They just want to feel better so they can return to work or activities, fully participate in family life, or not feel exhausted all the time. As such, a multimodal treatment plan is generally the best strategy for achieving a satisfactory improvement in symptoms.

Read about treating a case of continued pain after endometriosis treatment.

CASE 1 Patient’s pain continues after endometriosis excision

A 32-year-old woman (G1P1) reports having CPP for 8 years. She underwent excision of stage 1 endometriosis last year, which resulted in a modest improvement in pain for 6 months. Her pain is worse during menses, at the end of the day, and with vaginal intercourse (both during and lasting for 1 to 2 days after). On examination, you find diffuse pelvic floor tenderness but no adnexal masses or rectovaginal nodularity on palpation.

What treatment options would you consider for this patient?

Multimodal treatment often needed to manage CPP symptoms

The patient described in Case 1 may benefit from a combination of therapies that include analgesics, hormone suppression agents, and physical therapy (PT) (TABLE).

Analgesics

Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen and naproxen, work by inhibiting cyclooxygenase enzyme, which decreases assembly of peripheral prostaglandins and thromboxane. In a large Cochrane review, NSAIDs were associated with moderate or excellent pain relief for approximately 50% of patients with dysmenorrhea, and they have been shown to reduce menstrual flow due to decreased production of uterine prostaglandins.¹³ There is little evidence for use of NSAIDs in chronic pain conditions.

Acetaminophen’s mechanism of action is unclear, but the drug likely inhibits central prostaglandin synthesis, and it works synergistically with other analgesics.

Opioids act on μ and δ opioid receptors in the central and peripheral nervous systems as well as in the gastrointestinal system. No evidence supports opioid use in CPP or other chronic pain conditions. Long-term opioid use is associated with a multitude of adverse effects, risk for dependence, and the induction of opioid-induced hyperalgesia (in which patients develop greater sensitivity to pain stimuli).

Analgesics, specifically NSAIDs, can be considered for use in patients with dysmenorrhea, cyclic pain exacerbation, or a suspected inflammatory component of pain. Best practices include scheduling NSAID use before the onset of menses and continuing the drugs on a scheduled basis throughout. NSAIDs should be used for a brief period, and regular use on an empty stomach should be avoided.

Hormone suppression

Many types of hormone suppression therapy are available, including combined estrogen-progestin medications, progestin-only medications, and gonadotropin-releasing hormone (GnRH) agonists and antagonists.

Combined estrogen-progestin medications include oral contraceptive pills (OCPs), vaginal rings, and transdermal patches. Combined estrogen-progestin methods cause atrophy of eutopic and ectopic endometrium and suppress GnRH.

Progestin-only methods include oral formulations, the levonorgestrel intrauterine device, intramuscular and subcuticular injections, and subdermal implants. Progestin-only methods lead to atrophy of eutopic and ectopic endometrium.

A GnRH agonist, leuprolide depot works by downregulating luteinizing hormone and follicle stimulating hormone release from the pituitary, causing suppression of ovarian follicular development and ovulation, leading to a hypoestrogenic state.

Combined estrogen-progestin formulations and progestin-only options are often considered first-line therapy for dysmenorrhea and endometriosis.¹³ Continuous administration, with the goal of inducing amenorrhea, is effective in the treatment of dysmenorrhea. Several randomized controlled trials have shown that different types of hormone suppression agents are, essentially, equally effective.^13–15 Treatment recommendations therefore should focus on adverse effects, cost, and patient preference. GnRH agonists and norethindrone are not FDA approved for the treatment of endometriosis.

It may be appropriate to consider use of hormone suppression therapy in patients with menstrual exacerbation of pain symptoms, including those with a history of endometriosis. We generally advise patients that the goal is amenorrhea and that achieving it often involves a process of trying different formulations to find the best fit. Remember that GnRH agonists are dependent on a functional hypothalamic-pituitary-ovarian axis, and they are unlikely to be effective in women with suspected residual endometriosis who have had a bilateral oophorectomy.

Physical therapy

For CPP, PT typically targets musculoskeletal dysfunction in the pelvic floor, abdominal wall, hips, and back. Interventions include muscle control, mobilization, and biofeedback. Pelvic PT has been shown to improve pain and dyspareunia in patients with CPP, coccydynia, and vestibulodynia.^16–18 One large study found a significant, patient-directed decrease in pain medication use after pelvic floor PT.¹⁹ Pelvic PT for patients with interstitial cystitis and pelvic floor tenderness resulted in improved pain and bladder symptoms.²⁰

Pelvic PT can be considered for patients with pain reproducible with palpation of the pelvic floor, abdominal wall, paraspinal-lumbar muscles, or sacroiliac joints. Best practices include referral to a therapist who has specialized training in CPP, including pelvic floor therapy. It is important to clearly list the indication for referral, as many of these therapists also treat stress urinary incontinence. The wrong exercises can result in increased hypercontractility of pelvic floor muscles, which can worsen pelvic pain.

It is also critical to clarify expectations with your patient at the time of PT referral. Specifically, advise patients that when beginning therapy, it is common to experience a temporary increase in discomfort of the pelvic muscles. Inform patients also to expect that their therapist will perform internal manipulation of the pelvic floor muscles through the vagina, as this can be surprising for some patients. Finally, counsel patients that their adherence to daily home exercises improves their chance of a durable, long-term successful response.²¹

CASE 1 Treatment recommendations

For treatment of this patient’s CPP, consider scheduled naproxen therapy during menses, continuous OCPs, and referral for pelvic floor PT.

Read about treating a case of pain, sleep disturbance, and depression.

CASE 2 Patient with long-standing CPP, multiple diagnoses, and sleep problems

A 30-year-old woman (G2P2) reports having had CPP for 17 years. She is amenorrheic with continuous OCP treatment. She had experienced some improvement with pelvic PT. The patient reports that she has daily pain with intermittent pain flares and that she is exhausted and has poor sleep quality, which she attributes to pain. She has been diagnosed with interstitial cystitis, irritable bowel syndrome, and temporomandibular joint disorder. She has a history of depression, which she feels is well controlled with bupropion. Physical examination reveals that the patient has diffuse but mild pain in the pelvic floor and abdominal wall muscles.

What further pain management options can you offer for this patient?

Managing pain, sleep disturbance, and depression

This patient has been living with CPP for many years, and she has sleep difficulties that might be exacerbating pain or result from pain (or both). She is already on continuous OCPs and has had some relief with pelvic PT. Other options that may help with her multiple issues include antidepressants, cyclobenzaprine, and calcium channel blockers.

Antidepressants

Several classes of antidepressants have been used in the treatment of chronic pain conditions, specifically, tricyclic antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Commonly used TCAs include amitriptyline, nortriptyline, desipramine, and doxepin. Commonly used SNRIs are duloxetine and milnacipran. Both TCAs and SNRIs increase the availability of norepinephrine and serotonin, which are thought to act on the descending pain inhibitory systems to decrease pain sensitivity. Of note, most selective serotonin reuptake inhibitors (SSRIs) at typical doses do not exert a significant enough impact on norepinephrine to be useful for chronic pain.²²

Evidence is limited on the use of antidepressants for treating CPP. Amitriptyline is the most extensively studied antidepressant. Amitriptyline treatment resulted in modest pain improvement in patients with CPP and fibromyalgia.^23,24 Bothersome anticholinergic effects, including fatigue, dry mouth, and constipation, often are reported with TCAs. Adverse effects tend to be less with nortriptyline or desipramine compared with amitriptyline, but possibly at the expense of efficacy.

While SNRIs have not yet been studied in CPP, several investigations have shown that they improve pain and quality of life in fibromyalgia patients.^22,25

Antidepressant therapy may be appropriate for patients with suspected central pain amplification, widespread pain, and sleep disturbances. Best practices include patient education and careful discussion of this option with your patient. We suggest that clinicians explain that antidepressant medications alter the function of neurotransmitters, which modulate pain signals. While neurotransmitters also are involved in mood modulation, this is not the therapeutic goal in this circumstance. In addition, the doses used for the effective treatment of chronic pain are significantly lower than those needed to treat depression effectively.

Patients often need to hear that you believe that their pain is real and is not a manifestation of depression or another mood disorder. If you suspect that the patient also has untreated depression, address this as its own issue and use medications that have greater efficacy for mood symptoms.

Because many antidepressants can cause sedation, they are best taken before bedtime. Also, slow dose titration over several weeks will reduce the chance of bothersome adverse effects. Counsel patients that efficacy is not generally seen until at goal dose for several weeks. Be aware of interactions with other medications that can cause serotonin syndrome.

Cyclobenzaprine

Cyclobenzaprine is a muscle relaxant that also has activity in the central nervous system. The drug’s precise mechanism of action is not known, but it appears to potentiate norepinephrine and bind to serotonin receptors. Thus, it also likely has some TCA-like activity.

Cyclobenzaprine has not been studied in patients with CPP. In fibromyalgia patients, however, it produced significant improvements in pain, sleep, fatigue, and tenderness.^26,27 In our anecdotal experience with CPP patients, cyclobenzaprine has been one of the most impactful therapies. It hits the “chronic pain triad,” meaning that it helps with myofascial pain, neuropathic pain, and sleep disturbances.

Cyclobenzaprine treatment may be considered for patients with myofascial pain, sleep disturbances, and clinical symptoms of central pain amplification. Best practices include starting with low (5 mg) scheduled doses at bedtime and slowly titrating the dose. Drowsiness is a very common side effect, so we try to use that to the patient’s advantage to help with sleep quality.

Notably, sleep disturbances are highly prevalent in patients with chronic pain.²⁸ The relationship appears to be bidirectional, meaning that chronic pain negatively impacts sleep quality, and poor sleep quality causes amplified perception of pain.^28–30 Interventions that improve sleep quality have been associated with improvements in pain, coping, mood, and functional status.³¹ Helping a patient to improve her sleep generally requires a multifaceted approach. It always involves “sleep hygiene” or a behavioral component, and pharmacologic assistance may be considered when improved sleep hygiene does not provide adequately improved sleep quality.

Calcium channel blockers

Gabapentin and pregabalin are calcium channel blockers that inhibit the reuptake of glutamate, norepinephrine, and substance P, which helps to decrease pain sensitivity. They also act as membrane stabilizers, reducing hyperexcitability of peripheral and central nerves. Studies have shown that in patients with CPP, gabapentin resulted in improved pain and mood symptoms with few adverse effects.^23,32 Patients with fibromyalgia had improvements in pain, sleep, quality of life, fatigue, and anxiety with both gabapentin and pregabalin.³³

It is appropriate to consider use of gabapentin or pregabalin in patients with central pain amplification and sleep disturbances. Best practices include starting with a low dose at bedtime. Traditionally, gabapentin is given in 3 equal doses throughout the day. In our experience, patients report less daytime drowsiness and better sleep quality if two-thirds of the daily dose is given at night, with the remaining daily dose broken up into 2 smaller daytime doses. Slow titration over several weeks will reduce risk of bothersome adverse effects. Patients should be counseled that efficacy is not generally seen until treatment is at goal dose for several weeks.

CASE 2 Treatment recommendations

For this patient with daily pelvic pain, multiple diagnoses that have a pain component, and poor sleep quality, consider a treatment plan that includes scheduled cyclobenzaprine, improved sleep hygiene, and, if needed, gabapentin.

Read about treating a case of focal pain.

CASE 3 Cesarean delivery, hysterectomy, and continued pelvic pain

A 38-year-old woman (G2P2) has had CPP for the past 10 years. She developed persistent left lower-quadrant pain after cesarean delivery of her son. She had a hysterectomy 2 years ago for CPP, after which her pain worsened. She describes daily pain with intermittent flares. On examination, the patient has focal left lower-quadrant pain lateral to the left apex of her Pfannenstiel incision.

What treatment approach would be appropriate for this patient?

Focal pain requires a precisely targeted treatment

This patient with focal left lower-quadrant pain is a candidate for anesthetic trigger point injections in the affected area near her Pfannenstiel incision.

Anesthetic injections

Consider the presence of trigger points and peripheral neuropathy in patients with focal abdominal wall pain. Trigger points are focal, palpable nodules within muscles. They are markedly painful to palpation and are associated with referred pain, motor dysfunction, and occasionally autonomic symptoms. They frequently are seen in abdominal wall or pelvic floor muscles in patients with CPP and are caused by abnormal neuromuscular depolarization.

The ilioinguinal, iliohypogastric, and genitofemoral nerves are in close proximity to Pfannenstiel and laparoscopic port site incisions. These nerves may be injured directly during surgery, but they also may be compressed by postoperative scarring.

Anesthetics, such as lidocaine and bupivacaine, which act as sodium channel blockers, can be injected into this area, and improvement often substantially outlasts the anesthetic’s duration of action. While these drugs’ mechanism of action is not clear, theories include altered function of sodium channels on sensory nerves with repeated anesthetic exposure, dry needling that occurs during injection, hydrodissection of tight connective tissue bands surrounding neuromuscular bundles, or depletion of substance P and neuropeptides as a result of injection.^34,35

In several studies, patients with CPP reported decreased pain with lidocaine injections in pelvic floor or abdominal wall trigger points.^36–38 Patients with fibromyalgia reported improvement in pain and a decreased need for NSAIDs with bupivacaine trigger point injections.³⁹ While abdominal wall nerve blocks have not been extensively studied in patients with chronic neuropathic pain following gynecologic surgery, they have been shown to substantially improve chronic neuropathic pain following inguinal hernia repair.⁴⁰

Anesthetic injections appropriately may be considered in patients with focal pain in a muscle or in the distribution of abdominal wall nerves, palpation of which reproduces pain symptoms. Patients with diffuse pain are less likely to benefit from anesthetic injections. Best practices include careful examination with attention to areas of prior abdominal incisions.

Our practice is to inject each affected area with a mix of 9 mL of 1% lidocaine and 1 mL of sodium bicarbonate. If a patient reports at least 24 hours of improvement, we repeat the injection in 2 to 4 weeks. The goal is for the patient to experience a progressively longer duration of benefit with subsequent injections. We perform repeat injections shortly after pain begins to recur at that site. The patient should eventually graduate from receiving regular injections and may return for a remedial injection if pain recurs.

CASE 3 Treatment recommendations

For this patient with persistent focal left-lower quadrant pain and a defined trigger point near her Pfannenstiel incision, consider anesthetic injection in the left lower quadrant.

Work toward realistic symptom improvement

Remember that living with chronic pain is exhausting, and empathy with a patient-centered approach is the most important ingredient for patient improvement and satisfaction. Discuss realistic expectations with patients. Remind them that there is no magic bullet for the complex problem of CPP, and that chronic conditions generally do not improve overnight. Focus on improving the patient’s function and quality of life, and applaud symptom improvement rather than focusing on complete pain resolution.

As these visits often require a good deal of patient education, budget more appointment time if feasible. We find that scheduling frequent return visits (approximately every 3 to 4 months) allows timely treatment follow-up so that changes may be made if needed. If you have maximized your available treatment options, referring the patient to a specialist with additional training in CPP is a sensible next step.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Realistic prospective performance data are needed to quantify the additional benefit of the cytology component of cotesting on top of what is already known to be highly sensitive molecular HPV testing. While the addition of cytology to HPV testing can add performance, it also can add further costs and the potential for unnecessary colposcopies for what are merely cytomorphologic manifestations of an active HPV infection. Frequent invasive procedures such as colposcopy, which can be costly and lead to anxiety and distress in generally young women and the potential for overtreatment of likely regressive lesions, has been defined as a harm of screening by the US Preventive Services Task Force (USPSTF).

Details of the study

In a cohort from Kaiser Permanente Northern California, 1,208,710 women aged 30 years or older were screened with cotesting from 2003 to 2015. Those who cotested HPV negative and cytology negative were offered triennial screening. Positive cotest results were managed according to Kaiser protocol. Women with cytologic abnormalities were referred for colposcopy. Those with HPV positive/cytology negative results or HPV negative/cytology equivocal results underwent accelerated testing at 1 year. A total of 623 cervical cancers were identified and included in the analyses.

Using multiple analyses, Schiffman and colleagues demonstrated the sensitivity advantage of HPV testing. They clearly showed that the cytology component to cotesting performance over many years is very limited for detecting precancers and early curable cancers. For example, prediagnostic HPV testing (76.7%) was more likely to be positive than cytology (59.1%; P<.001 for paired comparison); 82.6% of all prediagnostic cotests were positive by HPV and/or cytology; and only 5.9% of the cotests were positive by cytology alone (HPV negative.)

Primary HPV testing is recommended as a potential screening strategy by an interim guidance group led by the Society of Gynecologic Oncology and the American Society for Colposcopy and Cervical Pathology, and it is the primary cervical cancer screening recommendation of USPSTF draft guidelines.¹ There have been reports that reliance on primary HPV testing would encourage cervical cancer mortality; Schiffman and colleagues point out, however, that according to their study data, such reports are overstated.

Despite these data, practically speaking, shifting away from standard cotesting poses numerous challenges for clinicians and laboratories alike; however, these data clearly show the limited value of cytology and, due to the overtreatment of likely regressive cervical intraepithelial neoplasia grade 2, the possible increased risk of preterm birth and its subsequent harm as well.

Study strengths and weaknesses

The authors examined the long-term relative history of HPV testing and cytology prior to cancer diagnosis in a large, prospectively followed US cohort where hundreds of women in this cohort developed cancer. There will not be a validation study of this size and scale in the near future. Further, the authors showed that the relative value of cytology to cotesting is minimal. Multiple subsequent rounds of cotesting after negative results also can be questioned. 

One weakness of the study is that the data were collected from only one health care system and therefore may not be representative of all populations. Additionally, cotesting was performed on 2 separately collected specimens, which may have reduced HPV testing performance.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Realistic prospective performance data are needed to quantify the additional benefit of the cytology component of cotesting on top of what is already known to be highly sensitive molecular HPV testing. While the addition of cytology to HPV testing can add performance, it also can add further costs and the potential for unnecessary colposcopies for what are merely cytomorphologic manifestations of an active HPV infection. Frequent invasive procedures such as colposcopy, which can be costly and lead to anxiety and distress in generally young women and the potential for overtreatment of likely regressive lesions, has been defined as a harm of screening by the US Preventive Services Task Force (USPSTF).

Details of the study

In a cohort from Kaiser Permanente Northern California, 1,208,710 women aged 30 years or older were screened with cotesting from 2003 to 2015. Those who cotested HPV negative and cytology negative were offered triennial screening. Positive cotest results were managed according to Kaiser protocol. Women with cytologic abnormalities were referred for colposcopy. Those with HPV positive/cytology negative results or HPV negative/cytology equivocal results underwent accelerated testing at 1 year. A total of 623 cervical cancers were identified and included in the analyses.

Using multiple analyses, Schiffman and colleagues demonstrated the sensitivity advantage of HPV testing. They clearly showed that the cytology component to cotesting performance over many years is very limited for detecting precancers and early curable cancers. For example, prediagnostic HPV testing (76.7%) was more likely to be positive than cytology (59.1%; P<.001 for paired comparison); 82.6% of all prediagnostic cotests were positive by HPV and/or cytology; and only 5.9% of the cotests were positive by cytology alone (HPV negative.)

Primary HPV testing is recommended as a potential screening strategy by an interim guidance group led by the Society of Gynecologic Oncology and the American Society for Colposcopy and Cervical Pathology, and it is the primary cervical cancer screening recommendation of USPSTF draft guidelines.¹ There have been reports that reliance on primary HPV testing would encourage cervical cancer mortality; Schiffman and colleagues point out, however, that according to their study data, such reports are overstated.

Despite these data, practically speaking, shifting away from standard cotesting poses numerous challenges for clinicians and laboratories alike; however, these data clearly show the limited value of cytology and, due to the overtreatment of likely regressive cervical intraepithelial neoplasia grade 2, the possible increased risk of preterm birth and its subsequent harm as well.

Study strengths and weaknesses

The authors examined the long-term relative history of HPV testing and cytology prior to cancer diagnosis in a large, prospectively followed US cohort where hundreds of women in this cohort developed cancer. There will not be a validation study of this size and scale in the near future. Further, the authors showed that the relative value of cytology to cotesting is minimal. Multiple subsequent rounds of cotesting after negative results also can be questioned. 

One weakness of the study is that the data were collected from only one health care system and therefore may not be representative of all populations. Additionally, cotesting was performed on 2 separately collected specimens, which may have reduced HPV testing performance.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Realistic prospective performance data are needed to quantify the additional benefit of the cytology component of cotesting on top of what is already known to be highly sensitive molecular HPV testing. While the addition of cytology to HPV testing can add performance, it also can add further costs and the potential for unnecessary colposcopies for what are merely cytomorphologic manifestations of an active HPV infection. Frequent invasive procedures such as colposcopy, which can be costly and lead to anxiety and distress in generally young women and the potential for overtreatment of likely regressive lesions, has been defined as a harm of screening by the US Preventive Services Task Force (USPSTF).

Details of the study

In a cohort from Kaiser Permanente Northern California, 1,208,710 women aged 30 years or older were screened with cotesting from 2003 to 2015. Those who cotested HPV negative and cytology negative were offered triennial screening. Positive cotest results were managed according to Kaiser protocol. Women with cytologic abnormalities were referred for colposcopy. Those with HPV positive/cytology negative results or HPV negative/cytology equivocal results underwent accelerated testing at 1 year. A total of 623 cervical cancers were identified and included in the analyses.

Using multiple analyses, Schiffman and colleagues demonstrated the sensitivity advantage of HPV testing. They clearly showed that the cytology component to cotesting performance over many years is very limited for detecting precancers and early curable cancers. For example, prediagnostic HPV testing (76.7%) was more likely to be positive than cytology (59.1%; P<.001 for paired comparison); 82.6% of all prediagnostic cotests were positive by HPV and/or cytology; and only 5.9% of the cotests were positive by cytology alone (HPV negative.)

Primary HPV testing is recommended as a potential screening strategy by an interim guidance group led by the Society of Gynecologic Oncology and the American Society for Colposcopy and Cervical Pathology, and it is the primary cervical cancer screening recommendation of USPSTF draft guidelines.¹ There have been reports that reliance on primary HPV testing would encourage cervical cancer mortality; Schiffman and colleagues point out, however, that according to their study data, such reports are overstated.

Despite these data, practically speaking, shifting away from standard cotesting poses numerous challenges for clinicians and laboratories alike; however, these data clearly show the limited value of cytology and, due to the overtreatment of likely regressive cervical intraepithelial neoplasia grade 2, the possible increased risk of preterm birth and its subsequent harm as well.

Study strengths and weaknesses

The authors examined the long-term relative history of HPV testing and cytology prior to cancer diagnosis in a large, prospectively followed US cohort where hundreds of women in this cohort developed cancer. There will not be a validation study of this size and scale in the near future. Further, the authors showed that the relative value of cytology to cotesting is minimal. Multiple subsequent rounds of cotesting after negative results also can be questioned. 

One weakness of the study is that the data were collected from only one health care system and therefore may not be representative of all populations. Additionally, cotesting was performed on 2 separately collected specimens, which may have reduced HPV testing performance.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

For many years, the approach to the diagnosis of hypertension was straight-forward—multiple blood pressure (BP) measurements ≥140/90 mm Hg established the diagnosis of hypertension, a disease associated with an increased risk of adverse cardiovascular events, including myocardial infarction and stroke. For more than a decade, hypertension experts have argued that a BP ≥130/80 mm Hg should establish the diagnosis of hypertension. Many clinicians resisted the change because it would markedly increase the number of asymptomatic adults with the diagnosis, increasing the number needing treatment. However, the findings of the Systolic Blood Pressure Intervention Trial (SPRINT) and other observational studies have catalyzed the American College of Cardiology (ACC) and the American Heart Association (AHA) to redefine normal BP as <120/80 mm Hg.¹ This change will expand the diagnosis of hypertension to include up to 50% of American adults.¹ In addition, the new definition of normal BP will result in the greater use of lifestyle interventions and antihypertensive medications to achieve the new normal, a BP of <120/80 mm Hg.

The new definition of hypertension

The new definition of hypertension is of particular importance for people at risk for developing cardiovascular disease (CVD) ^1,2 and is summarized here.

• Normal BP: systolic BP (SBP) <120 mm Hg and diastolic BP (DBP) <80 mm Hg
• Elevated BP: SBP 120–129 mm Hg and DBP <80 mm Hg
• Stage 1 hypertension: SBP 130–139 mm Hg or DBP 80–89 mm Hg.
• Stage 2 hypertension: SBP ≥140 mm Hg or DBP ≥90 mm Hg.

The new definition of hypertension will markedly increase the number of mid-life adults eligible to be treated for hypertension. I summarize the approach to treating hypertension in this article.

For mid-life adults, a SBP of <120 mm Hg is better for the heart
The heart is a pump, and not surprisingly, if a pump can achieve its job at a lower rather than a higher pressure, it is likely to last longer. The SPRINT study clearly demonstrated that in elderly hypertensive adults, an SBP target of <120 mm Hg is associated with fewer deaths than a SBP in the range of 130 to 140 mm Hg.³

In the SPRINT trial, 9,361 people with a mean age, body mass index, and BP of 68 years, 30 kg/m² and 140/78 mm Hg, respectively, were randomly assigned to intensive treatment of SBP to a goal of <120 mm Hg or to a target of <140 mm Hg. After 1 year of treatment, the intensive treatment group had a mean SBP of 121 mm Hg and the standard treatment group had a mean SBP of 136 mm Hg. To achieve a SBP <120 mm Hg, most patients required 3 antihypertensive medications, in contrast to the 2 antihypertensive medications typically needed to achieve a SBP in the range of 130 to 140 mm Hg.

After a median of 3.3 years of follow-up, significantly fewer deaths occurred in the intensive treatment group than in the standard treatment group, including deaths from all causes (3.3% vs 4.5%, P = .003) and deaths from CVD (0.8% vs 1.4%; P = .005). In addition, the risk of developing heart failure was lower in the intensive treatment than in the standard treatment group (1.3% vs 2.1%, P = .002). There was no difference between the 2 groups in the risk of stroke (1.3% vs 1.5%, P = .50) or myocardial infarction (2.1% vs 2.5%, P = .19). The rate of syncope was higher in the intensive treatment group (2.3% vs 1.7% in the standard treatment group, P = .05).³ Self-reported mental and physical health and satisfaction with treatment was similar in both groups.⁴

The investigators concluded that among people at risk for CVD, targeting a SBP of <120 mm Hg as compared to <140 mm Hg resulted in lower rates of heart failure and death, two clinically meaningful endpoints.

Read about nonpharmacologic interventions and antihypertensive medications to treat hypertension.

Diet and exercise

Nonpharmacologic interventions, including diet and exercise, are recommended for all people with a BP >120/80 mm Hg. In most situations, antihypertensive medications are not necessary if the patient has elevated BP (SBP 120–129 mm Hg and DBP <80 mm Hg) or Stage 1 hypertension (SBP 130–139 mm Hg or DBP 80–89 mm Hg) and a 10-year CVD risk of less than 10% using the ACC/AHA cardiovascular risk calculator⁵ (see http://www.cvriskcalcula tor.com/). For people at low risk for CVD, nonpharmacologic interventions, including diet and exercise, are often sufficient treatment.

The Dietary Approaches to Stop Hypertension (DASH) diet emphasizes increasing consumption of fruits, vegetables, low-fat dairy, whole-grains, fish, poultry, and nuts and decreasing the consumption of red meats, sugary drinks, sweets, sodium, and saturated and trans-fats. In randomized trials, the DASH diet is associated with a reduction in BP of approximately 5 mm Hg systolic and 3 mm Hg diastolic.⁶ The DASH trial monitored weight changes and adjusted calorie intake to ensure a stabilized weight throughout the study. Hence, the positive effect of the DASH diet was observed in the absence of any weight loss. Weight loss also can decrease BP with every 1- to 2-lb weight loss, reducing SBP by approximately 1 mm Hg.⁷ Combining the DASH diet with a low-sodium diet is especially important in people with high sodium intake, and is reported to reduce SBP by 5 to 20 mm Hg.⁸ Reducing the consumption of alcohol can result in a reduction of SBP and DBP in the range of 3 and 2 mm Hg, respectively.⁹

Exercising for 40 minutes, 3 to 4 times per week is associated with a reduction of SBP and DBP of approximately 5 and 3 mm Hg, respectively.¹⁰ Although the studies are of low quality, meditation is reported to decrease SBP and DBP by 4 and 2 mm Hg, respectively.¹¹

Antihypertensive medications

For all mid-life adults with Stage 2hypertension (SBP ≥140 mm Hg or DBP ≥90 mm Hg) or with both clinical CVD and Stage 1 hypertension, antihypertensive medications are recommended.¹ For people with Stage 1 hypertension and a 10-year CVD risk of ≥10%, antihypertensive medications are recommended. The target BP is <130/80 mm Hg for most people.

The recommended antihypertensive medications include thiazide diuretics, calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs). Many patients with Stage 2 hypertension will need treatment with 2 agents of different classes to achieve a BP <130/80 mm Hg. Some experts believe that an optimal 2-agent regimen includes an ACE or ARB plus a CCB based on the results of the ACCOMPLISH trial.¹² In this trial, 11,506 adults with hypertension and at very high risk for CVD, were randomly assigned to treatment with an ACE inhibitor plus CCB or with an ACE inhibitor plus hydrochlorothiazide. The BP achieved in both groups was approximately 132/73 mm Hg. The study was stopped after 3 years because participants in the ACE/thiazide group had a higher rate of adverse cardiovascular events (myocardial infarction, stroke, or death) than those in the ACE/CCB group (11.8% vs 9.6%; hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.72–0.90; P<.001). Compared to the ACE/thiazide group, the ACE/CCB group had a significantly lower rate of fatal and nonfatal myocardial infarction (2.2% vs 2.8%; HR, 0.78; 95% CI, 0.62–0.99; P = .04) and a lower rate of death from cardiovascular causes (1.9% vs 2.3%; HR, 0.80; 95% CI, 0.62–1.03, P = .08).

Worldwide, approximately 1 billion adults have a SBP ≥140 mm Hg.¹³ In the United States, 32% of adult women have Stage 2 hypertension or are taking an antihypertensive medication (TABLE).¹ There is a generally linear relationship between increasing SBP and DBP and an increased risk of a cardiovascular event, including heart failure, myocardial infarction, and stroke. An increase of SBP of 20 mm Hg or DBP of 10 mm Hg above a baseline BP of 115/75 mm Hg doubles the risk of death from CVD.¹⁴ For adults at risk for CVD, intensive treatment of hypertension clearly reduces the risk of a life-changing cardiovascular event.

It will probably take many years for the new SBP target of <120 mm Hg to be fully accepted by clinicians and patients because, although achieving a SBP of <120 mm Hg will decrease cardiovascular events, it is a very difficult target to achieve, requiring treatment with 3 antihypertensive medications for most patients. The early diagnosis and intensive treatment of hypertension is challenging because it requires clinicians to initiate a multi-decade course of treatment of asymptomatic people with the goal of preventing a life-altering cardiovascular event, including stroke and myocardial infarction.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

For many years, the approach to the diagnosis of hypertension was straight-forward—multiple blood pressure (BP) measurements ≥140/90 mm Hg established the diagnosis of hypertension, a disease associated with an increased risk of adverse cardiovascular events, including myocardial infarction and stroke. For more than a decade, hypertension experts have argued that a BP ≥130/80 mm Hg should establish the diagnosis of hypertension. Many clinicians resisted the change because it would markedly increase the number of asymptomatic adults with the diagnosis, increasing the number needing treatment. However, the findings of the Systolic Blood Pressure Intervention Trial (SPRINT) and other observational studies have catalyzed the American College of Cardiology (ACC) and the American Heart Association (AHA) to redefine normal BP as <120/80 mm Hg.¹ This change will expand the diagnosis of hypertension to include up to 50% of American adults.¹ In addition, the new definition of normal BP will result in the greater use of lifestyle interventions and antihypertensive medications to achieve the new normal, a BP of <120/80 mm Hg.

The new definition of hypertension

The new definition of hypertension is of particular importance for people at risk for developing cardiovascular disease (CVD) ^1,2 and is summarized here.

• Normal BP: systolic BP (SBP) <120 mm Hg and diastolic BP (DBP) <80 mm Hg
• Elevated BP: SBP 120–129 mm Hg and DBP <80 mm Hg
• Stage 1 hypertension: SBP 130–139 mm Hg or DBP 80–89 mm Hg.
• Stage 2 hypertension: SBP ≥140 mm Hg or DBP ≥90 mm Hg.

The new definition of hypertension will markedly increase the number of mid-life adults eligible to be treated for hypertension. I summarize the approach to treating hypertension in this article.

For mid-life adults, a SBP of <120 mm Hg is better for the heart
The heart is a pump, and not surprisingly, if a pump can achieve its job at a lower rather than a higher pressure, it is likely to last longer. The SPRINT study clearly demonstrated that in elderly hypertensive adults, an SBP target of <120 mm Hg is associated with fewer deaths than a SBP in the range of 130 to 140 mm Hg.³

In the SPRINT trial, 9,361 people with a mean age, body mass index, and BP of 68 years, 30 kg/m² and 140/78 mm Hg, respectively, were randomly assigned to intensive treatment of SBP to a goal of <120 mm Hg or to a target of <140 mm Hg. After 1 year of treatment, the intensive treatment group had a mean SBP of 121 mm Hg and the standard treatment group had a mean SBP of 136 mm Hg. To achieve a SBP <120 mm Hg, most patients required 3 antihypertensive medications, in contrast to the 2 antihypertensive medications typically needed to achieve a SBP in the range of 130 to 140 mm Hg.

After a median of 3.3 years of follow-up, significantly fewer deaths occurred in the intensive treatment group than in the standard treatment group, including deaths from all causes (3.3% vs 4.5%, P = .003) and deaths from CVD (0.8% vs 1.4%; P = .005). In addition, the risk of developing heart failure was lower in the intensive treatment than in the standard treatment group (1.3% vs 2.1%, P = .002). There was no difference between the 2 groups in the risk of stroke (1.3% vs 1.5%, P = .50) or myocardial infarction (2.1% vs 2.5%, P = .19). The rate of syncope was higher in the intensive treatment group (2.3% vs 1.7% in the standard treatment group, P = .05).³ Self-reported mental and physical health and satisfaction with treatment was similar in both groups.⁴

The investigators concluded that among people at risk for CVD, targeting a SBP of <120 mm Hg as compared to <140 mm Hg resulted in lower rates of heart failure and death, two clinically meaningful endpoints.

Read about nonpharmacologic interventions and antihypertensive medications to treat hypertension.

Diet and exercise

Nonpharmacologic interventions, including diet and exercise, are recommended for all people with a BP >120/80 mm Hg. In most situations, antihypertensive medications are not necessary if the patient has elevated BP (SBP 120–129 mm Hg and DBP <80 mm Hg) or Stage 1 hypertension (SBP 130–139 mm Hg or DBP 80–89 mm Hg) and a 10-year CVD risk of less than 10% using the ACC/AHA cardiovascular risk calculator⁵ (see http://www.cvriskcalcula tor.com/). For people at low risk for CVD, nonpharmacologic interventions, including diet and exercise, are often sufficient treatment.

The Dietary Approaches to Stop Hypertension (DASH) diet emphasizes increasing consumption of fruits, vegetables, low-fat dairy, whole-grains, fish, poultry, and nuts and decreasing the consumption of red meats, sugary drinks, sweets, sodium, and saturated and trans-fats. In randomized trials, the DASH diet is associated with a reduction in BP of approximately 5 mm Hg systolic and 3 mm Hg diastolic.⁶ The DASH trial monitored weight changes and adjusted calorie intake to ensure a stabilized weight throughout the study. Hence, the positive effect of the DASH diet was observed in the absence of any weight loss. Weight loss also can decrease BP with every 1- to 2-lb weight loss, reducing SBP by approximately 1 mm Hg.⁷ Combining the DASH diet with a low-sodium diet is especially important in people with high sodium intake, and is reported to reduce SBP by 5 to 20 mm Hg.⁸ Reducing the consumption of alcohol can result in a reduction of SBP and DBP in the range of 3 and 2 mm Hg, respectively.⁹

Exercising for 40 minutes, 3 to 4 times per week is associated with a reduction of SBP and DBP of approximately 5 and 3 mm Hg, respectively.¹⁰ Although the studies are of low quality, meditation is reported to decrease SBP and DBP by 4 and 2 mm Hg, respectively.¹¹

Antihypertensive medications

For all mid-life adults with Stage 2hypertension (SBP ≥140 mm Hg or DBP ≥90 mm Hg) or with both clinical CVD and Stage 1 hypertension, antihypertensive medications are recommended.¹ For people with Stage 1 hypertension and a 10-year CVD risk of ≥10%, antihypertensive medications are recommended. The target BP is <130/80 mm Hg for most people.

The recommended antihypertensive medications include thiazide diuretics, calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs). Many patients with Stage 2 hypertension will need treatment with 2 agents of different classes to achieve a BP <130/80 mm Hg. Some experts believe that an optimal 2-agent regimen includes an ACE or ARB plus a CCB based on the results of the ACCOMPLISH trial.¹² In this trial, 11,506 adults with hypertension and at very high risk for CVD, were randomly assigned to treatment with an ACE inhibitor plus CCB or with an ACE inhibitor plus hydrochlorothiazide. The BP achieved in both groups was approximately 132/73 mm Hg. The study was stopped after 3 years because participants in the ACE/thiazide group had a higher rate of adverse cardiovascular events (myocardial infarction, stroke, or death) than those in the ACE/CCB group (11.8% vs 9.6%; hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.72–0.90; P<.001). Compared to the ACE/thiazide group, the ACE/CCB group had a significantly lower rate of fatal and nonfatal myocardial infarction (2.2% vs 2.8%; HR, 0.78; 95% CI, 0.62–0.99; P = .04) and a lower rate of death from cardiovascular causes (1.9% vs 2.3%; HR, 0.80; 95% CI, 0.62–1.03, P = .08).

Worldwide, approximately 1 billion adults have a SBP ≥140 mm Hg.¹³ In the United States, 32% of adult women have Stage 2 hypertension or are taking an antihypertensive medication (TABLE).¹ There is a generally linear relationship between increasing SBP and DBP and an increased risk of a cardiovascular event, including heart failure, myocardial infarction, and stroke. An increase of SBP of 20 mm Hg or DBP of 10 mm Hg above a baseline BP of 115/75 mm Hg doubles the risk of death from CVD.¹⁴ For adults at risk for CVD, intensive treatment of hypertension clearly reduces the risk of a life-changing cardiovascular event.

It will probably take many years for the new SBP target of <120 mm Hg to be fully accepted by clinicians and patients because, although achieving a SBP of <120 mm Hg will decrease cardiovascular events, it is a very difficult target to achieve, requiring treatment with 3 antihypertensive medications for most patients. The early diagnosis and intensive treatment of hypertension is challenging because it requires clinicians to initiate a multi-decade course of treatment of asymptomatic people with the goal of preventing a life-altering cardiovascular event, including stroke and myocardial infarction.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

For many years, the approach to the diagnosis of hypertension was straight-forward—multiple blood pressure (BP) measurements ≥140/90 mm Hg established the diagnosis of hypertension, a disease associated with an increased risk of adverse cardiovascular events, including myocardial infarction and stroke. For more than a decade, hypertension experts have argued that a BP ≥130/80 mm Hg should establish the diagnosis of hypertension. Many clinicians resisted the change because it would markedly increase the number of asymptomatic adults with the diagnosis, increasing the number needing treatment. However, the findings of the Systolic Blood Pressure Intervention Trial (SPRINT) and other observational studies have catalyzed the American College of Cardiology (ACC) and the American Heart Association (AHA) to redefine normal BP as <120/80 mm Hg.¹ This change will expand the diagnosis of hypertension to include up to 50% of American adults.¹ In addition, the new definition of normal BP will result in the greater use of lifestyle interventions and antihypertensive medications to achieve the new normal, a BP of <120/80 mm Hg.

The new definition of hypertension

The new definition of hypertension is of particular importance for people at risk for developing cardiovascular disease (CVD) ^1,2 and is summarized here.

• Normal BP: systolic BP (SBP) <120 mm Hg and diastolic BP (DBP) <80 mm Hg
• Elevated BP: SBP 120–129 mm Hg and DBP <80 mm Hg
• Stage 1 hypertension: SBP 130–139 mm Hg or DBP 80–89 mm Hg.
• Stage 2 hypertension: SBP ≥140 mm Hg or DBP ≥90 mm Hg.

The new definition of hypertension will markedly increase the number of mid-life adults eligible to be treated for hypertension. I summarize the approach to treating hypertension in this article.

For mid-life adults, a SBP of <120 mm Hg is better for the heart
The heart is a pump, and not surprisingly, if a pump can achieve its job at a lower rather than a higher pressure, it is likely to last longer. The SPRINT study clearly demonstrated that in elderly hypertensive adults, an SBP target of <120 mm Hg is associated with fewer deaths than a SBP in the range of 130 to 140 mm Hg.³

In the SPRINT trial, 9,361 people with a mean age, body mass index, and BP of 68 years, 30 kg/m² and 140/78 mm Hg, respectively, were randomly assigned to intensive treatment of SBP to a goal of <120 mm Hg or to a target of <140 mm Hg. After 1 year of treatment, the intensive treatment group had a mean SBP of 121 mm Hg and the standard treatment group had a mean SBP of 136 mm Hg. To achieve a SBP <120 mm Hg, most patients required 3 antihypertensive medications, in contrast to the 2 antihypertensive medications typically needed to achieve a SBP in the range of 130 to 140 mm Hg.

After a median of 3.3 years of follow-up, significantly fewer deaths occurred in the intensive treatment group than in the standard treatment group, including deaths from all causes (3.3% vs 4.5%, P = .003) and deaths from CVD (0.8% vs 1.4%; P = .005). In addition, the risk of developing heart failure was lower in the intensive treatment than in the standard treatment group (1.3% vs 2.1%, P = .002). There was no difference between the 2 groups in the risk of stroke (1.3% vs 1.5%, P = .50) or myocardial infarction (2.1% vs 2.5%, P = .19). The rate of syncope was higher in the intensive treatment group (2.3% vs 1.7% in the standard treatment group, P = .05).³ Self-reported mental and physical health and satisfaction with treatment was similar in both groups.⁴

The investigators concluded that among people at risk for CVD, targeting a SBP of <120 mm Hg as compared to <140 mm Hg resulted in lower rates of heart failure and death, two clinically meaningful endpoints.

Read about nonpharmacologic interventions and antihypertensive medications to treat hypertension.

Diet and exercise

Nonpharmacologic interventions, including diet and exercise, are recommended for all people with a BP >120/80 mm Hg. In most situations, antihypertensive medications are not necessary if the patient has elevated BP (SBP 120–129 mm Hg and DBP <80 mm Hg) or Stage 1 hypertension (SBP 130–139 mm Hg or DBP 80–89 mm Hg) and a 10-year CVD risk of less than 10% using the ACC/AHA cardiovascular risk calculator⁵ (see http://www.cvriskcalcula tor.com/). For people at low risk for CVD, nonpharmacologic interventions, including diet and exercise, are often sufficient treatment.

The Dietary Approaches to Stop Hypertension (DASH) diet emphasizes increasing consumption of fruits, vegetables, low-fat dairy, whole-grains, fish, poultry, and nuts and decreasing the consumption of red meats, sugary drinks, sweets, sodium, and saturated and trans-fats. In randomized trials, the DASH diet is associated with a reduction in BP of approximately 5 mm Hg systolic and 3 mm Hg diastolic.⁶ The DASH trial monitored weight changes and adjusted calorie intake to ensure a stabilized weight throughout the study. Hence, the positive effect of the DASH diet was observed in the absence of any weight loss. Weight loss also can decrease BP with every 1- to 2-lb weight loss, reducing SBP by approximately 1 mm Hg.⁷ Combining the DASH diet with a low-sodium diet is especially important in people with high sodium intake, and is reported to reduce SBP by 5 to 20 mm Hg.⁸ Reducing the consumption of alcohol can result in a reduction of SBP and DBP in the range of 3 and 2 mm Hg, respectively.⁹

Exercising for 40 minutes, 3 to 4 times per week is associated with a reduction of SBP and DBP of approximately 5 and 3 mm Hg, respectively.¹⁰ Although the studies are of low quality, meditation is reported to decrease SBP and DBP by 4 and 2 mm Hg, respectively.¹¹

Antihypertensive medications

For all mid-life adults with Stage 2hypertension (SBP ≥140 mm Hg or DBP ≥90 mm Hg) or with both clinical CVD and Stage 1 hypertension, antihypertensive medications are recommended.¹ For people with Stage 1 hypertension and a 10-year CVD risk of ≥10%, antihypertensive medications are recommended. The target BP is <130/80 mm Hg for most people.

The recommended antihypertensive medications include thiazide diuretics, calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs). Many patients with Stage 2 hypertension will need treatment with 2 agents of different classes to achieve a BP <130/80 mm Hg. Some experts believe that an optimal 2-agent regimen includes an ACE or ARB plus a CCB based on the results of the ACCOMPLISH trial.¹² In this trial, 11,506 adults with hypertension and at very high risk for CVD, were randomly assigned to treatment with an ACE inhibitor plus CCB or with an ACE inhibitor plus hydrochlorothiazide. The BP achieved in both groups was approximately 132/73 mm Hg. The study was stopped after 3 years because participants in the ACE/thiazide group had a higher rate of adverse cardiovascular events (myocardial infarction, stroke, or death) than those in the ACE/CCB group (11.8% vs 9.6%; hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.72–0.90; P<.001). Compared to the ACE/thiazide group, the ACE/CCB group had a significantly lower rate of fatal and nonfatal myocardial infarction (2.2% vs 2.8%; HR, 0.78; 95% CI, 0.62–0.99; P = .04) and a lower rate of death from cardiovascular causes (1.9% vs 2.3%; HR, 0.80; 95% CI, 0.62–1.03, P = .08).

Worldwide, approximately 1 billion adults have a SBP ≥140 mm Hg.¹³ In the United States, 32% of adult women have Stage 2 hypertension or are taking an antihypertensive medication (TABLE).¹ There is a generally linear relationship between increasing SBP and DBP and an increased risk of a cardiovascular event, including heart failure, myocardial infarction, and stroke. An increase of SBP of 20 mm Hg or DBP of 10 mm Hg above a baseline BP of 115/75 mm Hg doubles the risk of death from CVD.¹⁴ For adults at risk for CVD, intensive treatment of hypertension clearly reduces the risk of a life-changing cardiovascular event.

It will probably take many years for the new SBP target of <120 mm Hg to be fully accepted by clinicians and patients because, although achieving a SBP of <120 mm Hg will decrease cardiovascular events, it is a very difficult target to achieve, requiring treatment with 3 antihypertensive medications for most patients. The early diagnosis and intensive treatment of hypertension is challenging because it requires clinicians to initiate a multi-decade course of treatment of asymptomatic people with the goal of preventing a life-altering cardiovascular event, including stroke and myocardial infarction.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Hormonal contraception (HC) has long been utilized safely in this country for a variety of indications, including pregnancy prevention, timing pregnancy appropriately, management of symptoms (dysmenorrhea, irregular menstrual cycles, heavy menstrual bleeding), and to prevent serious diseases (such as ovarian cancer, uterine cancer, osteoporosis in women with premature menopause). Like most prescription medications, there are potential adverse effects. With HC, side effects such as venous thromboembolism, a slight increase in liver cancer, and a possible increase in breast cancer risk have long been recognized.

Danish study compared HC use with breast cancer risk
In the December 7, 2017, issue of New England Journal of Medicine,¹ investigators in Denmark published a study of women using HC (oral, transdermal, intravaginal routes, and levonorgestrel intrauterine device [LNG-IUD]) and breast cancer risk compared with women who did not use HC. This retrospective observational country-wide study was very large (1.8 million women followed over an average of 10.9 years), which allowed for the detection of even small changes in breast cancer risk.

Putting results in perspective
It is important to point out that this is an observational study, and small effect sizes (1 in 7,600) should be interpreted with caution. Observational studies can introduce many different types of bias (prescribing bias, confounding bias, etc). Of note, while the LNG-IUD was associated with a small increased risk of breast cancer (relative risk [RR], 1.21; 95% confidence interval [CI], 1.11-1.33]), the higher dose continuous progestin administration (medroxyprogesterone) was not (RR, 0.95; 95% CI, 0.40-2.29).¹

Nonetheless, providing patients with a balanced summary of this new study along with other published and reliable information about HC that conveys both benefits and risks is important to assure that each woman makes a decision regarding HC that achieves her health and life goals. See "Counseling talking points" below.

Bottom line

This recent study demonstrated that in Denmark, a woman's risk of developing breast cancer is very slightly elevated on HC¹:

• 1 in 7,690 users overall
• 1 in 50,000 women older than age 35 years.

By comparison, the risk of maternal mortality in the United States is 1 in 3,788.² A substantial reduction in HC use would likely increase unintended and mistimed pregnancies with a potential substantial negative impact on quality of life and personal/societal cost.

The best available data indicate that a woman's risk of developing any cancer is slightly less on HC than not on HC, even with this incremental breast cancer increase.^3,4

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Hormonal contraception (HC) has long been utilized safely in this country for a variety of indications, including pregnancy prevention, timing pregnancy appropriately, management of symptoms (dysmenorrhea, irregular menstrual cycles, heavy menstrual bleeding), and to prevent serious diseases (such as ovarian cancer, uterine cancer, osteoporosis in women with premature menopause). Like most prescription medications, there are potential adverse effects. With HC, side effects such as venous thromboembolism, a slight increase in liver cancer, and a possible increase in breast cancer risk have long been recognized.

Danish study compared HC use with breast cancer risk
In the December 7, 2017, issue of New England Journal of Medicine,¹ investigators in Denmark published a study of women using HC (oral, transdermal, intravaginal routes, and levonorgestrel intrauterine device [LNG-IUD]) and breast cancer risk compared with women who did not use HC. This retrospective observational country-wide study was very large (1.8 million women followed over an average of 10.9 years), which allowed for the detection of even small changes in breast cancer risk.

Putting results in perspective
It is important to point out that this is an observational study, and small effect sizes (1 in 7,600) should be interpreted with caution. Observational studies can introduce many different types of bias (prescribing bias, confounding bias, etc). Of note, while the LNG-IUD was associated with a small increased risk of breast cancer (relative risk [RR], 1.21; 95% confidence interval [CI], 1.11-1.33]), the higher dose continuous progestin administration (medroxyprogesterone) was not (RR, 0.95; 95% CI, 0.40-2.29).¹

Nonetheless, providing patients with a balanced summary of this new study along with other published and reliable information about HC that conveys both benefits and risks is important to assure that each woman makes a decision regarding HC that achieves her health and life goals. See "Counseling talking points" below.

Bottom line

This recent study demonstrated that in Denmark, a woman's risk of developing breast cancer is very slightly elevated on HC¹:

• 1 in 7,690 users overall
• 1 in 50,000 women older than age 35 years.

By comparison, the risk of maternal mortality in the United States is 1 in 3,788.² A substantial reduction in HC use would likely increase unintended and mistimed pregnancies with a potential substantial negative impact on quality of life and personal/societal cost.

The best available data indicate that a woman's risk of developing any cancer is slightly less on HC than not on HC, even with this incremental breast cancer increase.^3,4

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Hormonal contraception (HC) has long been utilized safely in this country for a variety of indications, including pregnancy prevention, timing pregnancy appropriately, management of symptoms (dysmenorrhea, irregular menstrual cycles, heavy menstrual bleeding), and to prevent serious diseases (such as ovarian cancer, uterine cancer, osteoporosis in women with premature menopause). Like most prescription medications, there are potential adverse effects. With HC, side effects such as venous thromboembolism, a slight increase in liver cancer, and a possible increase in breast cancer risk have long been recognized.

Danish study compared HC use with breast cancer risk
In the December 7, 2017, issue of New England Journal of Medicine,¹ investigators in Denmark published a study of women using HC (oral, transdermal, intravaginal routes, and levonorgestrel intrauterine device [LNG-IUD]) and breast cancer risk compared with women who did not use HC. This retrospective observational country-wide study was very large (1.8 million women followed over an average of 10.9 years), which allowed for the detection of even small changes in breast cancer risk.

Putting results in perspective
It is important to point out that this is an observational study, and small effect sizes (1 in 7,600) should be interpreted with caution. Observational studies can introduce many different types of bias (prescribing bias, confounding bias, etc). Of note, while the LNG-IUD was associated with a small increased risk of breast cancer (relative risk [RR], 1.21; 95% confidence interval [CI], 1.11-1.33]), the higher dose continuous progestin administration (medroxyprogesterone) was not (RR, 0.95; 95% CI, 0.40-2.29).¹

Nonetheless, providing patients with a balanced summary of this new study along with other published and reliable information about HC that conveys both benefits and risks is important to assure that each woman makes a decision regarding HC that achieves her health and life goals. See "Counseling talking points" below.

Bottom line

This recent study demonstrated that in Denmark, a woman's risk of developing breast cancer is very slightly elevated on HC¹:

• 1 in 7,690 users overall
• 1 in 50,000 women older than age 35 years.

By comparison, the risk of maternal mortality in the United States is 1 in 3,788.² A substantial reduction in HC use would likely increase unintended and mistimed pregnancies with a potential substantial negative impact on quality of life and personal/societal cost.

The best available data indicate that a woman's risk of developing any cancer is slightly less on HC than not on HC, even with this incremental breast cancer increase.^3,4

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Access ACOG/SMFM algorithm for treatment of pregnant women with flu-like illness

Access ACOG/SMFM algorithm for treatment of pregnant women with flu-like illness

Access ACOG/SMFM algorithm for treatment of pregnant women with flu-like illness

A US Food & Drug Administration (FDA) Drug Safety Communication concerning a New Class Warning for all gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI) has been released. Gadolinium has been found to remain in patients’ bodies, including the brain, for months to years.¹

The FDA concluded that the benefit of all approved GBCAs outweighs any potential risks because gadolinium retention has not been directly linked to adverse health effects in patients with normal kidney function. To date, the only known adverse health effect related to gadolinium retention is a rare condition called nephrogenic systemic fibrosis that occurs in a small subgroup of patients with preexisting kidney failure. However, the FDA has recently received reports of adverse events involving multiple organ systems in patients with normal kidney function.¹

After a review by the Medical Imaging Drugs Advisory Committee, the FDA is requiring several actions¹:

• the development of a new Patient Medication Guide for GBCAs
• a requirement that every patient must read educational information before receiving a GBCA
• manufacturers of GBCAs must conduct human and animal studies to further assess the safety of these contrast agents.

FDA recommendations for your practice

The FDA advises that health care professionals should consider the retention characteristics of each agent when choosing a GBCA for patients who might be of higher risk for gadolinium retention.^1,2 These patients include¹:

• those requiring multiple lifetime doses
• pregnant women
• children
• patients with inflammatory conditions.

There are 2 types of GBCAs based on chemical structure: linear and macrocyclic. Linear GBCAs result in more retention and retention for a longer time than macrocyclic GBCAs.² A list of FDA-approved GBCAs with their chemical structures is found here: https://www.fda.gov/Drugs/DrugSafety/ucm589213.htm.²

Recommendations also state that repeated GBCA imaging studies be minimized when possible, particularly closely spaced MRI studies. However, necessary GBCA MRI scans should not be avoided or deferred.¹

Report adverse effects

Health care professionals and patients are encouraged to report adverse effects or side effects related to the use of GBCAs to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program found here: https://www.accessdata.fda.gov/scripts/medwatch/index.cfm?action=reporting.home.

A US Food & Drug Administration (FDA) Drug Safety Communication concerning a New Class Warning for all gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI) has been released. Gadolinium has been found to remain in patients’ bodies, including the brain, for months to years.¹

The FDA concluded that the benefit of all approved GBCAs outweighs any potential risks because gadolinium retention has not been directly linked to adverse health effects in patients with normal kidney function. To date, the only known adverse health effect related to gadolinium retention is a rare condition called nephrogenic systemic fibrosis that occurs in a small subgroup of patients with preexisting kidney failure. However, the FDA has recently received reports of adverse events involving multiple organ systems in patients with normal kidney function.¹

After a review by the Medical Imaging Drugs Advisory Committee, the FDA is requiring several actions¹:

• the development of a new Patient Medication Guide for GBCAs
• a requirement that every patient must read educational information before receiving a GBCA
• manufacturers of GBCAs must conduct human and animal studies to further assess the safety of these contrast agents.

FDA recommendations for your practice

The FDA advises that health care professionals should consider the retention characteristics of each agent when choosing a GBCA for patients who might be of higher risk for gadolinium retention.^1,2 These patients include¹:

• those requiring multiple lifetime doses
• pregnant women
• children
• patients with inflammatory conditions.

There are 2 types of GBCAs based on chemical structure: linear and macrocyclic. Linear GBCAs result in more retention and retention for a longer time than macrocyclic GBCAs.² A list of FDA-approved GBCAs with their chemical structures is found here: https://www.fda.gov/Drugs/DrugSafety/ucm589213.htm.²

Recommendations also state that repeated GBCA imaging studies be minimized when possible, particularly closely spaced MRI studies. However, necessary GBCA MRI scans should not be avoided or deferred.¹

Report adverse effects

Health care professionals and patients are encouraged to report adverse effects or side effects related to the use of GBCAs to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program found here: https://www.accessdata.fda.gov/scripts/medwatch/index.cfm?action=reporting.home.

A US Food & Drug Administration (FDA) Drug Safety Communication concerning a New Class Warning for all gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI) has been released. Gadolinium has been found to remain in patients’ bodies, including the brain, for months to years.¹

The FDA concluded that the benefit of all approved GBCAs outweighs any potential risks because gadolinium retention has not been directly linked to adverse health effects in patients with normal kidney function. To date, the only known adverse health effect related to gadolinium retention is a rare condition called nephrogenic systemic fibrosis that occurs in a small subgroup of patients with preexisting kidney failure. However, the FDA has recently received reports of adverse events involving multiple organ systems in patients with normal kidney function.¹

After a review by the Medical Imaging Drugs Advisory Committee, the FDA is requiring several actions¹:

• the development of a new Patient Medication Guide for GBCAs
• a requirement that every patient must read educational information before receiving a GBCA
• manufacturers of GBCAs must conduct human and animal studies to further assess the safety of these contrast agents.

FDA recommendations for your practice

The FDA advises that health care professionals should consider the retention characteristics of each agent when choosing a GBCA for patients who might be of higher risk for gadolinium retention.^1,2 These patients include¹:

• those requiring multiple lifetime doses
• pregnant women
• children
• patients with inflammatory conditions.

There are 2 types of GBCAs based on chemical structure: linear and macrocyclic. Linear GBCAs result in more retention and retention for a longer time than macrocyclic GBCAs.² A list of FDA-approved GBCAs with their chemical structures is found here: https://www.fda.gov/Drugs/DrugSafety/ucm589213.htm.²

Recommendations also state that repeated GBCA imaging studies be minimized when possible, particularly closely spaced MRI studies. However, necessary GBCA MRI scans should not be avoided or deferred.¹

Report adverse effects

Health care professionals and patients are encouraged to report adverse effects or side effects related to the use of GBCAs to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program found here: https://www.accessdata.fda.gov/scripts/medwatch/index.cfm?action=reporting.home.

Citation: Heazell HE, et al. Association between maternal sleep practices and late stillbirth – findings from a stillbirth case-control study. Published online November 20, 2017. DOI: 10.1111/1471-0528.14967.

Citation: Heazell HE, et al. Association between maternal sleep practices and late stillbirth – findings from a stillbirth case-control study. Published online November 20, 2017. DOI: 10.1111/1471-0528.14967.

Citation: Heazell HE, et al. Association between maternal sleep practices and late stillbirth – findings from a stillbirth case-control study. Published online November 20, 2017. DOI: 10.1111/1471-0528.14967.