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Menopause

By

JoAnn V. Pinkerton

, MD, University of Virginia Health System

Reviewed/Revised Jul 2023
View PATIENT EDUCATION
Topic Resources

Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary syndrome of menopause (symptoms and signs due to estrogen deficiency, such as vulvovaginal atrophy). Diagnosis is clinical, based retroactively on the absence of menses for 12 months. Manifestations may be treated (eg, with lifestyle modification, complementary and alternative medicine, nonhormonal therapy, and/or hormone therapy).

In the United States, the average age of physiologic menopause is 51 years old. Factors such as smoking, living at high altitude, and undernutrition may cause menopause to occur at a younger age.

The aging of the female reproductive system before and after menopause is described in stages (see table ).

  • Reproductive stage: Includes the time from menarche through the menopausal transition

  • Perimenopause: Refers to several years (duration varies greatly) before and the 1 year after the last menses; typically the most symptomatic phase because hormone levels are fluctuating

  • Menopausal transition: Occurs during the perimenopause stage; includes the typically 4 to 8 years that lead up to the final menstrual period; characterized by changes in the menstrual pattern; divided into early and late stages

  • Postmenopause: Refers to the time after the final menstrual period; divided into early and late stages

Premature ovarian failure Primary Ovarian Insufficiency In primary ovarian insufficiency, ovaries do not regularly release eggs and do not produce enough sex hormones despite high levels of circulating gonadotropins (especially follicle-stimulating... read more (primary ovarian insufficiency) is cessation of menses due to noniatrogenic ovarian failure before age 40. Contributory factors are thought to be primarily genetic or autoimmune.

Table

General references

  • 1. Paramsothy P, Harlow SD, Nan B, et al: Duration of the menopausal transition is longer in women with young age at onset: The multi-ethnic Study of Women's Health Across the Nation. Menopause 24 (2):142–149, 2017. doi: 10.1097/GME.0000000000000736

  • 2. El Khoudary SR, Greendale G, Crawford SL, et al: The menopause transition and women's health at midlife: a progress report from the Study of Women's Health Across the Nation (SWAN). Menopause 26(10):1213-1227, 2019. doi: 10.1097/GME.0000000000001424

Physiology of Menopause

As ovaries age, their response to the pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) decreases, initially causing the following:

  • A shorter follicular phase (with shorter and less regular menstrual cycles)

  • Fewer ovulations

  • Decreased progesterone production (see figure )

During the menopausal transition and postmenopause, estrogen levels fluctuate and eventually decrease significantly, but the changes in other hormones vary.

Estradiol levels can rise above normal if double ovulation and luteal out-of-phase (LOOP) events (ie, premature formation of a follicle due to the major surge in FSH during the luteal phase) occur. In general, the number of viable follicles decreases; eventually, the remaining follicles do not respond, and the ovaries produce very little estradiol. Estrogens continue to be produced by peripheral tissues (eg, fat, skin) from androgens (eg, androstenedione, testosterone). However, the total estrogen level gradually decreases during the 5 years after menopause, and estrone replaces estradiol as the most common estrogen.

Decreased levels of ovarian inhibin and estrogen, which inhibit pituitary release of LH and FSH, result in a substantial increase in circulating LH and FSH levels.

Changes in androgens around the time of menopause include a decrease in androstenedione levels by half. The decrease in testosterone, which begins in young adulthood, does not accelerate during menopause because the stroma of the postmenopausal ovary and adrenal gland continue to secrete substantial amounts.

Superficial cells in the vagina are lost, leading to a more alkaline pH. As a result, the number of lactobacilli decreases and pathogenic bacteria overgrow, increasing the risk of vaginal infections and inflammation.

Symptoms and Signs of Menopause

Changes in the menstrual cycle usually begin during a woman’s 40s, with variation in cycle length. A persistent difference in consecutive menstrual cycle length of ≥ 7 days defines early menopausal transition. Skipping ≥ 2 cycles defines late menopausal transition.

The marked fluctuations in estrogen levels may contribute to other perimenopausal symptoms and signs such as

  • Breast tenderness

  • Changes in menstrual flow

  • Moodiness

  • Exacerbation of menstrual migraines

Symptoms can last from 6 months to > 10 years and range from nonexistent to severe.

Vasomotor

Hot flushes (hot flashes) and/or night sweats due to vasomotor instability affect 75 to 85% of women and usually begin before menses stop. Vasomotor symptoms last an average of 7.4 years and can persist for > 10 years in some groups of women (1 Symptoms and signs references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ).

Women feel warm or hot and may perspire, sometimes profusely; core temperature increases. The skin, especially of the face, head, and neck, may become red and warm. The episodic flush, which may last from 30 seconds to 5 minutes, may be followed by chills. Flushes may manifest during the night as night sweats.

Other etiologies of hot flushes or night sweats should also be considered (eg, lymphoma Overview of Lymphoma , tuberculosis Tuberculosis (TB) Tuberculosis (TB) , mycobacteria avium Nontuberculous Mycobacterial Infections ), particularly if these symptoms do not occur around the time of menopause or do not respond to hormone therapy.

The mechanism of hot flushes is unknown, but they are thought to result from changes in the thermoregulatory center located in the hypothalamus. The range of core body temperatures that is comfortable to the woman decreases; as a result, a very small increase in core body temperature can trigger heat release as a hot flush.

In a survey study from 1996 to 2017 in the United States, women who self-identified as Black had the highest prevalence and longest duration of hot flashes and were most bothered by them, while the prevalence in those who identified as Japanese or Chinese was the lowest and prevalence in self-identified Hispanic and White women was in-between the range (2 Symptoms and signs references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ). Lower socioeconomic status was associated with an increased incidence of hot flashes, independent of race/ethnicity.

Vaginal

Vaginal symptoms include dryness, dyspareunia, and occasionally irritation and itching. As estrogen production decreases, vulvar and vaginal mucosae become thinner, drier, more friable, and less elastic, and vaginal rugae are lost.

Genitourinary syndrome of menopause includes symptoms and signs due to estrogen and androgen deficiency such as

  • Vulvovaginal atrophy

  • Urinary urgency

  • Dysuria

  • Frequent urinary tract infections and/or vaginitis

Neuropsychiatric

Neuropsychiatric changes (eg, poor concentration, memory loss, depressive symptoms, anxiety) may transiently accompany menopause. Many women experience these symptoms during perimenopause and assume that menopause is the cause. However, evidence supporting a connection between menopause and these symptoms is mixed (3 Symptoms and signs references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ). Also, these symptoms are not directly related to the decreases in estrogen levels that occur with menopause.

Recurrent night sweats can contribute to insomnia, fatigue, irritability, and poor concentration by disrupting sleep. However, during menopause, sleep disturbances are common even among women who do not have hot flushes.

Cardiovascular

After menopause, levels of low-density lipoprotein (LDL) cholesterol increase in women. Levels of high-density lipoprotein (HDL) cholesterol remain about the same as before menopause. The change in LDL levels may partly explain why atherosclerosis and thus coronary artery disease become more common among women after menopause. However, whether these changes result from aging or from the decrease in estrogen levels after menopause is unclear. Until menopause, the high estrogen levels may protect against coronary artery disease.

Musculoskeletal

Up to 20% of bone density loss occurs during the first 5 years after menopause. After this period of rapid bone loss, the age-related rate of bone loss in women is similar to that in men.

Other symptoms

Menopause is a normal, healthy phase in a woman's life, but each woman has a unique experience.

Quality of life may decrease if symptoms are severe or if less common symptoms of menopause, such as joint aches and pains, develop. For some women (eg, those with a history of endometriosis, dysmenorrhea, menorrhagia, premenstrual syndrome, or menstrual migraine), quality of life improves after menopause.

Some postmenopausal women experience burning mouth syndrome Burning Mouth Syndrome .

Symptoms and signs references

  • 1. Avis NE, Crawford SL, Greendale G, et al: Duration of menopausal vasomotor symptoms over the menopause transition (Study of Women's Health Across the Nation). JAMA Intern Med 175 (4):531–539, 2015. doi: 10.1001/jamainternmed.2014.8063

  • 2. El Khoudary SR, Greendale G, Crawford SL, et al: The menopause transition and women's health at midlife: a progress report from the Study of Women's Health Across the Nation (SWAN). Menopause 26(10):1213-1227, 2019. doi:10.1097/GME.0000000000001424

  • 3. Gold EB, Sternfeld B, Kelsey JL, et al: Relation of demographic and lifestyle factors to symptoms in a multi-racial/ethnic population of women 40-55 years of age. Am J Epidemiol 152(5):463-473, 2000. doi:10.1093/aje/152.5.463

Diagnosis of Menopause

  • Menstrual history

  • Rarely follicle-stimulating hormone (FSH) levels

Timing of cessation of ovarian function is categorized based on age, as follows:

  • Premature menopause: < 40 years old

  • Early menopause: 40 to 45 years old

  • Menopause (typical age range): > 45 years old

Diagnosis of menopause is clinical; it is confirmed retroactively when a woman has had no menses for 12 months and there is no other suspected cause.

Vulvovaginal atrophy on pelvic examination supports the diagnosis.

FSH levels may be measured, but this test is rarely necessary except perhaps in women who have had a hysterectomy and in women who are younger than the usual age of menopause. A single measurement may not be informative, because levels fluctuate during the menopausal transition. Consistently elevated levels confirm menopause.

Treatment of Menopause

  • Nonpharmacologic measures (eg, cognitive-behavioral therapy, clinical hypnosis)

  • Hormone therapy (estrogens, progestogens, and selective estrogen receptor modulators)

  • Nonhormonal medications (eg, selective serotonin reuptake inhibitors, neurokinin receptor antagonists)

Treatment of menopause is symptomatic (eg, to relieve hot flushes and symptoms due to vulvovaginal atrophy).

Patient education about the physiologic causes of menopause and possible symptoms and signs helps patients manage the changes that occur.

Nonpharmacologic measures

Stellate ganglion blockade is also effective for vasomotor symptoms of menopause (8 Treatment references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ). This procedure is also to treat migraine and complex regional pain syndrome and involves injection of an anesthetic at the lower cervical or upper thoracic region of the anterior cervical spine.

Many different types of nonpharmacologic interventions have been suggested to manage menopausal symptoms. The following measures are not recommended by the North American Menopause Society because there are insufficient or negative data about their efficacy in reducing vasomotor symptoms (1 Treatment references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ):

  • Cooling techniques (eg, lowering the thermostat, using fans, layered or light clothing, cooling sheets or other bedding)

  • Avoiding triggers (eg, spicy food, alcohol, caffeine)

  • Dietary modifications

  • Exercise

  • Yoga

  • Relaxation

  • Paced respiration (taking several slow, deep breaths with inhaling through the nose and exhaling through the mouth)

  • Mindfulness-based interventions

  • Chiropractic interventions

  • Acupuncture

  • Calibration of neural oscillations

Many of these interventions have other health benefits and a low potential for harm. For example, a healthy diet is important for health promotion and chronic disease prevention, and exercise, yoga, and relaxation techniques may improve sleep and reduce stress. Individual women may find some of these measures helpful for vasomotor symptoms. However, clinicians should counsel women against using unproven methods that are invasive or have other potential for harm (eg, extreme diets). In addition, the benefits of unproven treatments do not outweigh the burden on patients if measures are expensive, time-consuming, or physically demanding.

Over-the-counter vaginal lubricants and moisturizers help relieve vaginal dryness. Sexual intercourse or other vaginal stimulation helps preserve vaginal elasticity in menopausal patients.

Hormone therapy

Hormone therapy Menopausal Hormone Therapy Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more with estrogen, a progestogen, or both is the most effective treatment for menopausal symptoms. To prevent endometrial neoplasia in women with a uterus (ie, have not had a hysterectomy), estrogen must be given in combination with a progestogen (to oppose the effect of estrogen on the endometrium); the exception to this is very low dose vaginal estrogen therapy (used for genitourinary syndrome of menopause), which can be given without a progestogen. Another option for women with a uterus is the combination of conjugated estrogens with bazedoxifene.

Selective estrogen receptor modulators (SERMs)

Ospemifene, a SERM, can be used to treat dyspareunia due to vaginal atrophy if women are not able to self-administer vaginal estrogen therapy or vaginal dehydroepiandrosterone (eg, if they have severe arthritis). Ospemifene may increase the risk of venous thrombosis.

Bazedoxifene Choice of systemic hormone therapy is given with conjugated estrogens and does not require concurrent use of a progestogen; it can relieve hot flushes, improve sleep, prevent bone loss, and lessen symptoms of vaginal atrophy.

In women at high risk of breast cancer and in need of prevention of bone loss or fracture, raloxifene may be used with risks of slight increase in hot flashes, leg cramps, or venous thrombosis. No increased risk of stroke was seen but, in women at high risk of cardiac disease, a small increase in fatal stroke was seen (9 Treatment references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ).

The SERMs tamoxifen and raloxifene have been used primarily for their antiestrogenic properties and not to relieve menopausal symptoms.

Nonhormonal medications

In well-designed, randomized controlled trials, nonhormonal medications that have proven efficacy for management of vasomotor symptoms are as follows (however, all of these medications are less effective than hormone therapy) (1 Treatment references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ):

  • Neurokinin receptor antagonists

  • Selective serotonin reuptake inhibitors (SSRIs)

  • Serotonin-norepinephrine reuptake inhibitors (SNRIs)

  • Gabapentin

  • Oxybutynin

For fezolinetant, potential side effects include abdominal pain, diarrhea, difficulty sleeping, back pain, hot flushes, and rare reports of liver injury. Liver function tests are needed before starting fezolinetant and every 3 months for first 9 months of treatment. Fezolinetant is contraindicated in patients using CYP1A2 inhibitors (eg, ciprofloxacin, cimetidine, and other medications).

Oxybutynin, an anticholinergic that is used to treat overactive bladder, also effectively treats vasomotor symptoms (doses in studies have included 2.5 or 5 mg twice daily; or up to 15 mg extended-release once daily) (13 Treatment references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ). Gabapentin (300 mg up to 3 times daily) has been shown to be effective and well-tolerated (14 Treatment references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ). However, pregabalin is not recommended due to limited efficacy data and risk of adverse effects, including potential substance misuse. Other nonhormonal medications that are not recommended are suvorexant (a dual orexin-receptor antagonist), due to limited efficacy data, and clonidine, because it is less effective than other nonhormonal treatment options (1 Treatment references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ).

Herbal or dietary supplements

A wide variety of dietary supplements have been suggested to manage menopausal symptoms. There are no supplements with proven efficacy for vasomotor symptoms, and their use is not recommended by the North American Menopause Society (1 Treatment references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ).

Supplements that have limited or inconsistent evidence of benefit include soy food and soy extracts, soy metabolite equol, pollen extract, ammonium succinate, lactobacillus acidophilus, and rhubarb. Supplements with no demonstrated evidence of benefit include black cohosh, evening primrose oil, wild yam, omega-3 fatty acid, and cannabinoids.

Some herbal preparations or other supplements interact with other medications. Because not all complementary and alternative medicine therapies are efficacious and safe, clinicians should discuss the risks and benefits of these therapies to make sure that women are well-informed (15 Treatment references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ).

Treatment references

  • 1. The 2023 nonhormone therapy position statement of The North American Menopause Society. Menopause 30(6):573-590, 2023. doi:10.1097/GME.0000000000002200

  • 2. Mann E, Smith MJ, Hellier J, et al: Cognitive behavioural treatment for women who have menopausal symptoms after breast cancer treatment (MENOS 1): a randomised controlled trial. Lancet Oncol 13(3):309-318, 2012. doi:10.1016/S1470-2045(11)70364-3

  • 3. Ayers B, Smith M, Hellier J, Mann E, Hunter MS: Effectiveness of group and self-help cognitive behavior therapy in reducing problematic menopausal hot flushes and night sweats (MENOS 2): a randomized controlled trial. Menopause 19(7):749-759, 2012. doi:10.1097/gme.0b013e31823fe835

  • 4. Elkins G, Marcus J, Stearns V, et al: Randomized trial of a hypnosis intervention for treatment of hot flashes among breast cancer survivors. J Clin Oncol 26(31):5022-5026, 2008. doi:10.1200/JCO.2008.16.6389

  • 5. Elkins GR, Fisher WI, Johnson AK, et al: Clinical hypnosis in the treatment of postmenopausal hot flashes: a randomized controlled trial. Menopause 20(3):291-298, 2013. doi:10.1097/gme.0b013e31826ce3ed

  • 6. Thurston RC, Ewing LJ, Low CA, et al: Behavioral weight loss for the management of menopausal hot flashes: A pilot study. Menopause 22 (1):59–65, 2015. doi: 10.1097/GME.0000000000000274

  • 7. Huang AJ, Subak LL, Wing R, et al: An intensive behavioral weight loss intervention and hot flushes in women [published correction appears in Arch Intern Med 170(17):1601, 2010]. Arch Intern Med 170(13):1161-1167, 2010. doi:10.1001/archinternmed.2010.162

  • 8. Walega DR, Rubin LH, Banuvar S, et al: Effects of stellate ganglion block on vasomotor symptoms: findings from a randomized controlled clinical trial in postmenopausal women. Menopause 21(8):807-814, 2014. doi:10.1097/GME.0000000000000194

  • 9. Liu JH: Selective estrogen receptor modulators (SERMS): keys to understanding their function. Menopause 27(10):1171-1176, 2020. doi:10.1097/GME.0000000000001585

  • 10. Johnson KA, Martin N, Nappi RE, et al: Efficacy and safety of fezolinetant in moderate-to-severe vasomotor symptoms associated with menopause: a phase 3 RCT [published online ahead of print, 2023 Feb 3]. J Clin Endocrinol Metab dgad058, 2023. doi:10.1210/clinem/dgad058

  • 11. Lederman S, Ottery FD, Cano A, et al: Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet 401(10382):1091-1102, 2023. doi:10.1016/S0140-6736(23)00085-5

  • 12. Pinkerton JV, Redick DL, Homewood LN, Kaunitz AM: Neurokinin receptor antagonist, fezolinetant, for treatment of menopausal vasomotor symptoms [published online ahead of print, 2023 Apr 25]. J Clin Endocrinol Metab dgad209, 2023. doi:10.1210/clinem/dgad209

  • 13. Simon JA, Gaines T, LaGuardia KD; Extended-Release Oxybutynin Therapy for VMS Study Group: Extended-release oxybutynin therapy for vasomotor symptoms in women: a randomized clinical trial. Menopause 23(11):1214-1221, 2016. doi:10.1097/GME.0000000000000773

  • 14. Loprinzi CL, Diekmann B, Novotny PJ, et al: Newer antidepressants and gabapentin for hot flashes: a discussion of trial duration. Menopause 16(5):883-887, 2009. doi:10.1097/gme.0b013e31819c46c7

  • 15. Johnson A, Roberts L, Elkins G: Complementary and alternative medicine for menopause. J Evid Based Integr Med 24:2515690X19829380, 2019. doi: 10.1177/2515690X19829380

Menopausal Hormone Therapy

Hormone therapy (estrogen, a progestogen, or both) is the most effective treatment for menopausal symptoms (1 Hormone therapy references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ). It is used to relieve vasomotor and other systemic menopausal symptoms, treat symptoms due to vulvovaginal atrophy, and, for some patients, prevent or treat osteoporosis.

Menopausal hormone therapy improves quality of life for many women by relieving their symptoms but does not improve quality of life for and should not be routinely given to asymptomatic postmenopausal women.

If hormone therapy is needed to control menopausal symptoms, clinicians should determine the most appropriate type, dose, route of administration, and duration, based on goals of treatment and individual health risks. Potential benefits and harms due to hormone therapy should be periodically reevaluated.

For healthy women with bothersome menopausal symptoms who are < 60 years old or < 10 years past menopause onset, potential benefits of hormone therapy are most likely to exceed potential harms. For women at risk of bone loss or fracture, hormone therapy reduces bone loss and incidence of fractures and can be used in women who are not candidates for first-line medications for osteoporosis.

Starting hormone therapy in women who are > 60 years old or > 10 to 20 years past menopause onset is not generally recommended (1 Hormone therapy references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ). In these women, potential harms of hormone therapy (eg, coronary artery disease, stroke, venous thromboembolism, dementia) are likely to exceed potential benefits.

Unless the clinical recommendation is clear, shared decision-making is recommended because of the following:

  • Potential benefits and harms of hormone therapy can be complicated.

  • The net benefit and harm can be marginal.

  • Health risks may change with age.

Choice of systemic hormone therapy

Women who have a uterus (ie, have not had a hysterectomy) are usually given estrogen, and this must be given in combination with a progestogen (progesterone or synthetic progestin), because unopposed estrogen increases risk of endometrial hyperplasia and cancer.

For systemic estrogen therapy, oral, transdermal (patch, lotion, spray, or gel), or vaginal forms may be used. Treatment should start with the lowest dose; the dose is increased every 2 to 4 weeks as needed. Doses vary by preparation. Examples of preparations and low doses for systemic therapy include

  • 0.3 mg conjugated estrogen orally once daily

  • 0.5 mg estradiol orally once daily

  • 0.014 to 0.375 mg a day estradiol as a patch applied to the skin once or twice weekly

  • 0.05mg a day estradiol vaginal ring inserted every 3 months

There are also daily estradiol skin gels and sprays available in varying doses.

The progestogen is taken continuously (ie, daily) or sequentially (cyclically; 12 to 14 consecutive days of every 4 week). Examples of preparations and doses are

Bleeding due to progestogen withdrawal is less likely with continuous therapy, although irregular bleeding can occur during the first 6 to 9 months of therapy.

Combination products of estrogen and a progestogen are available as pills and transdermal patches.

  • Pills (eg, 0.3 mg conjugated estrogens plus medroxyprogesterone acetate 1.5 mg once daily; norethindrone acetate 0.1 mg plus estradiol 0.5 mg once daily)

  • Patches (eg, estradiol 0.045 mg plus levonorgestrel 0.015 mg a day released by a patch applied to the skin once weekly)

For women who have had a hysterectomy, systemic estrogen therapy is used alone.

An alternative to systemic estrogen therapy is combination conjugated estrogen/bazedoxifene (a selective estrogen receptor modulator [ SERM Genitourinary syndrome of menopause treatment Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ]). This is a good option for women with a history of breast tenderness or bleeding on estrogen therapy and those with a family history of breast cancer. Bazedoxifene acts as an estrogen receptor antagonist in the endometrium and protects against endometrial cancer; thus, a progestogen is not needed. Conjugated estrogen/bazedoxifene relieves hot flushes, improve sleep, prevent bone loss, and lessen symptoms of vaginal atrophy. Benefits of conjugated estrogen/bazedoxifene include a lower incidence of breast tenderness and abnormal uterine bleeding than with other forms of menopausal hormone therapy; incidence is similar to that with placebo. Breast density and incidence of breast cancer did not increase in women who were followed for 2 years (2 Hormone therapy references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ). Risk of venous thromboembolism is similar to that with estrogen, but conjugated estrogen/bazedoxifene appears to protect the endometrium and potentially the breast. Bazedoxifene as a single medication is not available in the United States.

Progestogens are sometimes used alone (eg, medroxyprogesterone acetate 10 mg orally once a day or depot 150 mg IM once a month, megestrol acetate 10 to 20 mg orally once a day, micronized progesterone 300 mg nightly) when estrogen is contraindicated, but they are not as effective as estrogen for hot flushes and do not relieve vaginal dryness. Micronized progesterone in peanut oil is contraindicated in women who are allergic to peanuts. Newer combination products do not contain peanut oil. The effect on bone density of progestogen-alone menopausal hormone therapy is uncertain. Bone density is decreased with use of certain progestogen contraceptives (depot medroxyprogesterone acetate Progestin Contraceptive Injections Various contraceptive progestin injections are available worldwide. Depot medroxyprogesterone acetate (DMPA) is a long-acting injectable formulation of medroxyprogesterone acetate in a crystalline... read more ), and there is no effect with others (levonorgestrel intrauterine devices Intrauterine Device (IUDs; IUD) In the United States, 12% of women who use contraception use intrauterine devices (IUDs). IUDs are popular because of their advantages as a contraceptive method, including being highly effective... read more ).

Genitourinary syndrome of menopause treatment

When the only symptoms are urogenital, vaginal hormone therapy is preferred. Topical forms (eg, creams; vaginal tablets, suppositories, or rings) may be more effective for urogenital symptoms than oral forms and are sometimes used in addition to systemic therapy if these symptoms are not adequately treated.

Vaginal estradiol tablets, suppositories, rings, or creams in low doses (eg, 4 or 10 mcg for tablets, 7.5 mcg rings, 0.5 mg estradiol cream) deliver less estrogen to the systemic circulation. When vaginal estrogen is used at the lowest recommended doses, a progestogen is not needed. However, higher doses of vaginal estrogen can deliver as much estrogen as oral or transdermal therapy and, if given to women who still have a uterus, require the addition of a progestogen. Any vaginal bleeding in women taking hormone therapy, whether systemic or vaginal, should be immediately evaluated to rule out endometrial cancer.

When low-dose vaginal estrogen or DHEA or ospemifene is used, a progestogen is not needed; however, there are no long-term endometrial safety data for these medications (1 Hormone therapy references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ).

Ospemifene, a SERM, can be used to treat dyspareunia due to vaginal atrophy if women are not able to self-administer vaginal estrogen therapy or dehydroepiandrosterone (eg, if they have severe arthritis) or if they prefer to use an oral medication other than estrogen (4 Hormone therapy references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ). In women who have recently been taking hormone therapy, hot flushes may temporarily increase, but in most women, hot flushes resolve after about 6 weeks. Ospemifene may increase the risk of venous thrombosis.

For moderate to severe genitourinary symptoms, treatments include

  • Intravaginal estrogen

  • Intravaginal DHEA

  • Systemic hormone therapy

  • Ospemifene

Osteoporosis management

Estrogen therapy has beneficial effects on bone density and reduces the incidence of fractures in postmenopausal women (not particularly those with osteoporosis). In one large study, hormone therapy reduced the incidence of fractures by 24% (6 Hormone therapy references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ). Nonetheless, estrogen therapy (with or without a progestogen) is usually not recommended as first-line treatment or as prophylaxis for osteoporosis. When osteoporosis or prevention of osteoporosis is the only concern, clinicians should consider starting hormone therapy if the following apply:

Risks and adverse effects

Risks with systemic estrogen therapy or combined estrogen/progestogen therapy include

Estrogen therapy may be contraindicated in women who have had or are at high risk of breast cancer, stroke, coronary artery disease, or thrombosis.

The risk of endometrial cancer is higher in women who have a uterus and are given unopposed estrogen therapy. Nevertheless, any vaginal bleeding in a woman on any type of hormone therapy should immediately be evaluated to rule out endometrial cancer.

The risk of breast cancer begins to increase after 3 to 5 years of combination therapy when the standard dose (eg, conjugated estrogen 0.625 mg and medroxyprogesterone acetate at 2.5 mg once/day) is used (7 Hormone therapy references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ). In the Women's Health Initiative randomized trial that compared oral conjugated estrogens with or without medroxyprogesterone acetate, when estrogen was used alone, risk of breast cancer was slightly lower at 7 years, but this benefit appeared to disappear after 10 to 15 years of use (8 Hormone therapy references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ).

The risk of venous thromboembolism and stroke may be lower with low-dose transdermal estrogen rather than oral estrogen. Older postmenopausal women (> 10 years past menopause or > 60 years old when they start hormone therapy) are at higher risk of coronary artery disease when they are given oral standard dose combination therapy (9 Hormone therapy references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more , 10 Hormone therapy references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ).

Data on dementia are mixed. Among participants ≥ 65 years old in the Women's Health Initiative trial, menopausal hormone therapy increased dementia risk, with results for combination conjugated estrogens and medroxyprogesterone acetate more adverse than for estrogens alone (9 Hormone therapy references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ). But for those aged 50 to 55 years at randomization, neutral results were seen at an average of 7.2 years post-intervention.

Incidence of gallbladder disease and urinary incontinence may be increased with systemic combination therapy or estrogen alone. However, low-dose vaginal estrogen therapy decreases incidence of recurrent urinary tract infections and improves stress and urgency incontinence (11 Hormone therapy references Menopause is the permanent cessation of menses (amenorrhea) due to loss of ovarian follicular function. Clinical manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ). Risk of all these disorders is very low in healthy women who take hormone therapy for a short time after menopause.

Progestogens may have adverse effects (eg, abdominal bloating, breast tenderness, increased breast density, headache, increased LDL); micronized progesterone appears to have fewer adverse effects, but may cause drowsiness (which can be minimized by taking at bedtime). Progestogens may increase the risk of thrombosis. There are no long-term safety data for progestogens.

Before prescribing hormone therapy and periodically as therapy continues, clinicians should discuss its risks and benefits with women.

Hormone therapy references

  • 1. The 2022 Hormone Therapy Position Statement of The North American Menopause Society Advisory Panel: The 2022 hormone therapy position statement of The North American Menopause Society. Menopause 9(7):767-794, 2022. doi:10.1097/GME.0000000000002028

  • 2. Pinkerton JV, Pickar JH, Racketa J, et al: Bazedoxifene/conjugated estrogens for menopausal symptom treatment and osteoporosis prevention. Climacteric 15 (5):411–418, 2012. doi: 10.3109/13697137.2012.696289

  • 3. Labrie F, Archer DF, Koltun W, et al: Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause 23 (3):243–256, 2016. doi: 10.1097/GME.0000000000000571

  • 4. Constantine G, Graham S, Portman DJ, et al: Female sexual function improved with ospemifene in postmenopausal women with vulvar and vaginal atrophy: Results of a randomized, placebo-controlled trial. Climacteric 18 (2): 226–232, 2015. doi:10.3109/13697137.2014.954996

  • 5. Faubion SS, Larkin LC, Stuenkel CA, et al: Management of genitourinary syndrome of menopause in women with or at high risk for breast cancer: consensus recommendations from The North American Menopause Society and The International Society for the Study of Women's Sexual Health. Menopause 2 5(6):596–608, 2018. doi: 10.1097/GME.0000000000001121

  • 6. Rossouw JE, Anderson GL, Prentice RL, et al: Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial. JAMA 288 (3):321–333, 2002. doi:10.1001/jama.288.3.321

  • 7. Chlebowski RT, Hendrix SL, Langer RD, et al: Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial. JAMA 289(24):3243-3253, 2003. doi:10.1001/jama.289.24.3243

  • 8. Chlebowski RT, Rohan TE, Manson JE, et al: Breast cancer after use of estrogen plus progestin and estrogen alone: analyses of data from 2 Women's Health Initiative randomized clinical trials. JAMA Oncol 1(3):296-305, 2015. doi:10.1001/jamaoncol.2015.0494

  • 9. Manson JE, Chlebowski RT, Stefanick ML, et al: Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA 310(13):1353-1368, 2013. doi:10.1001/jama.2013.278040

  • 10. Cho L, Kaunitz AM, Faubion SS, et al: Rethinking Menopausal Hormone Therapy: For Whom, What, When, and How Long?. Circulation 147(7):597-610, 2023. doi:10.1161/CIRCULATIONAHA.122.061559

  • 11. Christmas MM, Iyer S, Daisy C, et al: Menopause hormone therapy and urinary symptoms: a systematic review [published online ahead of print, 2023 May 16]. Menopause 10.1097/GME.0000000000002187, 2023. doi:10.1097/GME.0000000000002187

Key Points

  • In the United States, menopause occurs at an average age of 51.

  • Symptoms of menopause tend to be maximal during the few years before and the year after menopause (during perimenopause), except for symptomatic vulvovaginal atrophy, which may worsen over time.

  • Up to 20% of bone density loss occurs during the first 5 years after menopause, followed by age-related rate of bone loss similar to that in men.

  • Consider menopause confirmed if a woman who is an appropriate age and who is not pregnant has not had menses for 12 months.

  • For vaginal dryness or dyspareunia due to menopause, recommend vaginal stimulation and over-the-counter vaginal lubricants and moisturizers, and if they are ineffective, consider low-dose vaginal estrogen creams, tablets, suppositories, or rings; other options include oral ospemifene or intravaginal DHEA suppositories.

  • Before prescribing hormone therapy and periodically as therapy continues, talk to women about the potential benefits and harms (eg, deep venous thrombosis, pulmonary embolism, stroke, breast cancer; low risk of gallbladder disease, stress urinary incontinence); potential harms are greater for women who start hormone therapy after age 60 or who are > 10 to 20 years past menopause onset.

  • If women choose hormone therapy to relieve hot flushes, prescribe estrogen plus, for women with a uterus, a progestogen or prescribe conjugated estrogen/bazedoxifene.

  • Individualize treatment with hormone therapy to maximize benefits and minimize harms, and periodically reevaluate benefits and harms; low-dose transdermal hormone therapy may have less risk of deep venous thrombosis and stroke.

  • Consider SSRIs (eg, paroxetine salt), SNRIs (eg, venlafaxine), neurokinin receptor antagonists (eg, fezolinetant), and gabapentin as alternatives to hormone therapy for relieving hot flushes.

  • Effective nonpharmacologic options include cognitive-behavioral therapy, hypnosis, and possibly weight loss.

Additional Information

The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

  • Pinkerton JV: Hormone Therapy for Postmenopausal Women. N Engl J Med 382(5):446-455, 2020. doi:10.1056/NEJMcp1714787

Drugs Mentioned In This Article

Drug Name Select Trade
Alora, Climara, Delestrogen, Depgynogen, Depo-Estradiol, Depogen, Divigel, DOTTI, Elestrin, Esclim, Estrace, Estraderm, Estrasorb, Estring, EstroGel, Evamist, FemPatch, Femring, Femtrace, Gynodiol , Gynogen LA, Imvexxy, LYLLANA, Menostar, Minivelle, Vagifem, Valergen, Vivelle, Vivelle-Dot, Yuvafem
Crinone, Endometrin , First - Progesterone MC 10, First - Progesterone MC 5, Prochieve, PROMETRIUM
Cenestin, Enjuvia, Premarin
Osphena
Evista
Nolvadex, Soltamox
Active-PAC with Gabapentin, Gabarone , Gralise, Horizant, Neurontin
Ditropan, Ditropan XL, Gelnique , Oxytrol, Oxytrol for Women
Brisdelle, Paxil, Paxil CR, Pexeva
VEOZAH
Cetraxal , Ciloxan, Cipro, Cipro XR, OTIPRIO, Proquin XR
Acid Reducer, Major Acid Reducer, Tagamet, Tagamet HB
Lyrica, Lyrica CR
Belsomra
Catapres, Catapres-TTS, Duraclon, Kapvay, NEXICLON XR
Acidophilus, Acidophilus Gold Extra Strength, BioGaia, Culturelle, Culturelle Health & Wellness, Culturelle Health & Wellness Vegetarian, Culturelle Kids, Culturelle Kids Probiotic, Culturelle Kids Pro-well Probiotics, Culturelle Kids Purely Probiotic, Culturelle Kids Regularity, Culturelle Probiotics, Culturelle Probiotics Health & Wellness, Culturelle Probiotics Total Balance, Florajen, Floranex Granules, Lacto Freedom , Mega Probiotic, NewFlora, PROBACAP, Probiotic, Probiotic Acidophilus, REJUVAFLOR, RENEWAFLOR, UpSpring DUAL
No brand name available
Amen, Depo-Provera, Depo-subQ Provera 104, Provera
AfterPill, EContra EZ, EContra One-Step, Fallback Solo, Kyleena , LILETTA, Mirena, My Choice, My Way, Next Choice, Next Choice One Dose, Norplant, Opcicon One-Step, Plan B, Plan B One-Step , Preventeza, React, Skyla, Take Action
Aygestin, Camila, Deblitane 28-Day, Errin , Heather, Jencycla, Jolivette , Lyza, Nora-BE, Norlyroc, Nor-QD, Ortho Micronor, Sharobel 28-Day
Megace, Megace ES
Effexor, Effexor XR, Venlafaxine
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