US Pharm. 2023;48(9):26-32.

ABSTRACT: Women of childbearing age and those in the perimenopausal, menopausal, and postmenopausal stages of life may experience a number of health problems that can greatly impact their reproductive health and overall quality of life. An individualized treatment plan, including nonhormonal pharmacologic and nonpharmacologic interventions, may be recommended to treat common conditions such as dysmenorrhea and vaginal candidiasis in women of childbearing age and vasomotor symptoms and osteoporosis in women moving through the stages of menopause. As medication experts, pharmacists in the community setting can utilize their specialized knowledge and skills to increase their patients’ access to healthcare, especially regarding women’s health issues.

Women of childbearing age and those in the perimenopausal, menopausal, and postmenopausal stages of life may face a number of health issues that can greatly impact their reproductive health and overall quality of life. For example, some problems that women of childbearing age may experience include dysmenorrhea, yeast infection, and lack of prenatal care. The reported prevalence of dysmenorrhea varies; a literature review of 15 studies revealed estimates ranging from 67% to 90% in young women aged 17 to 24 years and 15% to 75% in older adult women.1 The CDC notes that vaginal candidiasis is the second most common type of vaginal infection in the United States, with an estimated 1.4 million outpatient clinic visits related to this condition taking place each year.2 In the U.S., the lack of prenatal care is another significant health issue for women. March of Dimes reported that one in 16 U.S. infants (equating to 6.3% of live births) was born to a woman who received late or no prenatal care.3

Owing to declining estrogen levels over time, women in the perimenopausal, menopausal, and postmenopausal stages of life are at increased risk for developing hormone-associated disorders (e.g., vasomotor and genitourinary problems, osteoporosis, dyslipidemia, cardiovascular events) that can impact overall health. Nearly 80% of U.S. women experience vasomotor symptoms during the menopausal stage.4 Moreover, 25% of women have reported having these bothersome symptoms daily, with an estimated average of four to five episodes of hot flashes each day.4

Postmenopausal osteoporosis is another significant health problem for U.S. women. The Endocrine Society reports that osteoporosis affects about 10% of postmenopausal women aged >60 years worldwide.5 A variety of pharmacotherapies (e.g., prescription medications, herbal supplements) and nonpharmacologic interventions can effectively treat women’s health disorders across the life span. For example, nonsteroidal anti-inflammatory drugs (e.g., naproxen, ibuprofen) are used to treat dysmenorrhea in women of childbearing age, and selective serotonin reuptake inhibitors ([SSRIs]; e.g., paroxetine, sertraline) and gabapentin are prescribed for vasomotor symptoms (e.g., hot flashes, night sweats) associated with menopause.

Pharmacists are trained to serve as the medication expert on the healthcare team; therefore, they are ideally suited to provide patient education as well as pharmacologic and nonpharmacologic therapy recommendations for women’s health issues. As the U.S. healthcare landscape continues to shift toward a more value-based model, pharmacists can collaborate with other healthcare providers (e.g., physicians, nurse practitioners) to increase access to healthcare services, particularly those related to women’s health, by using their specialized knowledge and skills.6

Childbearing Age

Dysmenorrhea: Dysmenorrhea, a condition characterized by painful menstrual cramps, affects 50% to 90% of women of reproductive age, with about 10% to 15% of them experiencing severe and sometimes disabling pain.7 Dysmenorrhea-related pain typically occurs in the lower abdomen and ranges from mild to severe. There are two types of dysmenorrhea. Primary dysmenorrhea, the more prevalent type, is not caused by an underlying medical condition; in contrast, secondary dysmenorrhea is due to an underlying condition, typically endometriosis or uterine fibroids.1 One nonpharmacologic intervention, heat therapy (e.g., applying a hot water bottle, taking a warm bath), alleviates cramps by increasing blood flow and relaxing the pelvic muscles.8 Dietary modifications that reduce caffeine and salt intake minimize water retention and inflammation, potentially lessening cramp severity.9 The anti-inflammatory and analgesic properties of herbal remedies such as ginger and cinnamon can also relieve menstrual pain.10

Yeast Infection: This fungal infection, which is prevalent in women of childbearing age, develops when there is an overgrowth of the fungus normally present in the vaginal area. Multiple factors disrupt the normal balance of the vaginal microbiota. The hormonal changes that occur during the menstrual cycle and pregnancy increase a woman’s susceptibility to developing yeast infections.11 Antibiotic use, a weakened immune system, uncontrolled diabetes mellitus, sexual activity, and the use of certain hygiene products are additional risk factors.12 Nonpharmacologic interventions are highly effective in preventing and managing yeast infections. Practicing good personal hygiene (e.g., keeping the genital area clean and dry) helps maintain a healthy balance of vaginal flora and reduces infection risk.13 Wearing breathable underwear and avoiding tight-fitting clothing also prevent yeast overgrowth by enhancing air circulation and reducing moisture.2 Douches, scented products, and other potential irritants that disrupt the vaginal ecosystem should be avoided.12 Probiotics containing Lactobacillus strains combat yeast infections by promoting the growth of beneficial vaginal bacteria and inhibiting harmful Candida growth.14 Incorporating probiotics and yogurt with live and active cultures into the diet also supports optimal vaginal health.

Prenatal Health and Pregnancy: Preparing the body for pregnancy is a crucial component of ensuring a healthy, viable pregnancy. Eating a balanced diet, maintaining an ideal body weight, exercising regularly, and avoiding harmful substances all foster optimal preconception health. A healthy diet includes nutrient-rich foods such as fruits, vegetables, whole grains, lean proteins, and dairy products, all of which provide essential vitamins and minerals important for fertility and early fetal development.15 Avoiding tobacco, alcohol, and illicit drugs significantly reduces the risk of infertility, miscarriage, and fetal-development problems.16 Folic acid and folate reduce the risk of neural-tube defects.15 Iron facilitates oxygen transport, which is especially important during pregnancy, when the maternal blood volume increases.17 Omega-3 fatty acids support healthy fetal brain and eye development, and calcium and vitamin D support fetal bone, neuromuscular, cardiovascular, and hematologic health.15 Nutritional supplements—which are intended to complement rather than replace a balanced diet—bridge dietary gaps and help meet the pregnant woman’s increased nutrient requirements, thereby promoting a healthy pregnancy.

Perimenopause

Perimenopause, the transitional period when a woman experiences irregularities in her menstrual cycle, lasts for an average of 4 years. This transition usually begins between ages 45 and 55 years, with the average age at menopause being 51 years.18 Perimenopause ends when a woman has been period-free for 12 months, at which point she is considered menopausal.19 During perimenopause, ovarian function declines, resulting in a progressive reduction in estrogen levels.20 This and other hormonal changes contribute to numerous genitourinary (e.g., vaginal dryness, irritation, burning, and itching), vasomotor (i.e., hot flashes, night sweats), and psychological (e.g., anxiety, anger, irritability) symptoms. A hot flash is a sudden, recurrent feeling of heat that may be accompanied by flushing and sweating. As the sweating cools the body, chilling may occur. Hot flashes, which are experienced by 75% of women, may vary in intensity and frequency; most episodes last between 30 seconds and 10 minutes.18,21 Hot flashes that occur at night are called night sweats. Hormonal changes increase the risk of adverse dyslipidemia, cardiovascular events, and osteoporosis.22

Mild perimenopausal symptoms may not require treatment. Both hormonal and nonhormonal therapeutic strategies are used to manage bothersome perimenopausal symptoms.19 The majority of the OTC products marketed as treatments for perimenopause are herbal supplements, many of which are available online as well as in stores. These complementary and alternative medicine (CAM) products contain various ingredients, including black cohosh, ashwagandha, and soy isoflavones. Cissus quadrangularis (CQR-300), magnolia bark, milk thistle, ginkgo biloba, calcium, and various root extracts and vitamins may also be included in supplement formulations. Other frequently used agents include dong quai, evening primrose oil, and St. John’s wort.

Black Cohosh: This herb native to North America is found in numerous perimenopausal and menopausal OTC products. The mechanism of action of black cohosh is unclear. It was initially thought to activate estrogen receptors, but some research has suggested little or negligible estrogenic effect.23 More studies need to be conducted; however, black cohosh is considered generally safe and effective for alleviating hot flashes.24 Some studies have suggested that black cohosh may be beneficial for managing the anxiety, insomnia, and sweating that can accompany perimenopause.25 The most commonly used dosage of one commercially available black cohosh product (Remifemin) is 20 mg twice daily, although 40 mg twice daily has also been used.26 Patients taking black cohosh may experience gastrointestinal (GI) side effects (e.g., vomiting, diarrhea, nausea) and, less commonly, liver toxicity.27

Ashwagandha: The extract from this evergreen shrub found in Asia and Africa is widely considered a safe and effective option for managing perimenopausal symptoms.28 Marketed as an herbal supplement, ashwagandha is touted for its ability to manage anxiety, stress, depression, insomnia, sexual function, and fatigue; improve mental alertness; aid in weight loss; and combat inflammation and pain.29 A recent prospective, randomized, double-blind, placebo-controlled study reported that ashwagandha was effective in managing stress, anxiety, and sleep over an 8-week period.28 Ashwagandha’s mechanism of action is thought to involve agonism at gamma-aminobutyric acid receptors as well as potential anti-inflammatory and antioxidant effects.30 Reported dosages range from 250 mg to 600 mg daily.31 Patients taking ashwagandha may develop mild GI side effects (e.g., vomiting, diarrhea, nausea).32 Concerningly, use of this herb has been linked to alterations in hepatic enzymes and to hepatic toxicity.32 To date, many of the studies conducted to empirically investigate the claims for ashwagandha’s beneficial effects have had small sample sizes.32 More rigorous studies of herb-drug interactions also must be conducted. Potential drug interactions between ashwagandha and medications used to treat thyroid imbalances, hyperglycemia, and hypertension might be predicted since the herb is implicated in raising thyroid-hormone levels, lowering cortisol and blood glucose levels, and lowering blood pressure.33-35

Soy Isoflavones: Soy contains a high concentration of isoflavones, which are plant phytoestrogens that function similarly to human estrogen.36,37 Specifically, isoflavones mimic estrogen in the body (albeit with much weaker effects) by binding to estrogen receptors.37 In this regard, soy isoflavones elicit either weak estrogenic or antiestrogenic activity and potentially alleviate hot flashes.37 Although some studies have reported positive outcomes in alleviating other perimenopausal issues, including urogenital (e.g., frequent urinary tract infections), psychological (e.g., anxiety, depression), and somatic (e.g., hot flashes, sleeping problems) symptoms, there is no consensus in the literature regarding soy isoflavones’ overall utility.37,38 One study found that 900 mg daily was a safe and effective dosage.36 Patients should be warned about the possibility of headaches and GI side effects (e.g., constipation, diarrhea), and the use of soy isoflavones in patients with estrogen-dependent cancer may be inappropriate.38,39

Efficacy of CAM Therapies: Although some women using CAM therapies report relief from hot flashes and other postmenopausal symptoms, studies are inconsistent, as the benefit may be similar to that seen with placebo. Dong quai has been used for female hormonal balancing in traditional Chinese medicine; however, it does not appear effective for hot flashes and may cause photosensitivity, anticoagulation, and certain cancers. Evening primrose oil is commonly used to treat inflammatory and autoimmune disorders; it is also used for hot flashes but does not seem to be effective in this regard.40 St. John’s wort improves mood and anxiety disorders in premenopausal and postmenopausal women, but it should not be combined with SSRIs or serotonin-norepinephrine reuptake inhibitors.41

Postmenopause

Menopause marks the end of a woman’s reproductive years.41 The hormonal changes that occur before and after menopause have both physical and psychological effects. Many of the symptoms commonly experienced postmenopausally are the same as those occurring during perimenopause, including vasomotor dysfunction (i.e., hot flashes), insomnia, depression and anxiety, and increased bone loss, and they may persist for several years into the postmenopausal period. The treatment approaches for perimenopausal and postmenopausal symptoms are therefore similar. Postmenopausal hormone therapy is the most effective treatment for moderate-to-severe vasomotor symptoms; it is also beneficial for depression, insomnia, and preventing bone loss.41 Depression may worsen during the menopausal transition and postmenopausally, and women with a history of depression are more likely to experience a recurrence.41

Symptom Management: Mild postmenopausal symptoms may not require treatment. If the symptoms are not bothersome, exercise, a healthy diet, and nonpharmacologic measures may be sufficient for symptom control and prevention of bone loss. Treatment of vasomotor symptoms, mood disorders, and/or insomnia should be considered if the symptoms are unbearable, disrupt sleep, or adversely affect quality of life.41 All postmenopausal women should adopt dietary and nonpharmacologic measures to prevent bone loss.

Nonpharmacologic Measures: Hot flashes, night sweats, depression, and life-related stressors may contribute to insomnia. Mild insomnia may be effectively managed with good sleep hygiene and—if needed—occasional short-term use of an OTC agent such as melatonin or diphenhydramine.42 To help manage hot flashes and night sweats, patients should layer clothing and bedding; keep the room temperature cooler; and use a small portable fan.43 Patients should also avoid alcohol, spicy foods, and caffeine; adhere to a healthy diet; exercise regularly; and maintain a healthy weight.43 Mindfulness meditation and relaxation techniques such as hypnotherapy, meditation, acupuncture, and yoga seem to be effective, and cognitive-behavioral therapy may be beneficial.44 Collectively, these measures may help reduce menopause-related insomnia, mood disorders, and stress.

Calcium and Vitamin D for Preventing Bone Loss: All postmenopausal women should be encouraged to maintain adequate calcium and vitamin D intake, exercise regularly, stop smoking, and limit alcohol intake. In 2011, the Institute of Medicine (IOM; now known as the National Academy of Medicine) set recommended daily allowances for calcium and vitamin D and recommended daily intake for magnesium, all of which are important for maintaining bone health. The IOM’s recommendations are: calcium, 1,000 mg/day for women aged ≤50 years and 1,200 mg/day for those aged >50 years; vitamin D, 600 IU for women aged ≤70 years and 800 IU for those aged >70 years; and magnesium, 320 mg/day for women of all ages.41

The Pharmacist’s Role

The Pharmacists as Front-Line Responders for COVID-19 Patient Care: Executive Summary states that pharmacists are the most accessible healthcare providers, as nearly 90% of people in the U.S. live within 5 miles of a community pharmacy.45 Patients visit a community pharmacy an average of 35 times per year, compared with only four visits per year to their primary care provider.6 Pharmacists are well situated to utilize their specialized knowledge and skills to improve patients’ access to and quality of healthcare, especially regarding commonly experienced women’s health issues. As medication experts, pharmacists must be prepared to make OTC self-care therapy recommendations when appropriate. They should counsel patients about nonpharmacologic interventions that may be effective while also providing information on FDA-approved prescription medications used to treat common women’s health issues. Pharmacists should also make sure to discuss data on the safety and efficacy of herbal supplements, which are not regulated by the FDA for quality, safety, and efficacy.

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