Update on the Management of Menopause and Perimenopausal Symptoms

Educational Objectives

The goal of this program is to improve patient care for menopausal symptoms. After hearing and assimilating this program, the clinician will be better able to:

1. Recognize menopausal and perimenopausal symptoms.
2. Cite diagnostic and screening recommendations for various menopausal symptoms.
3. Choose hormonal and nonhormonal therapy for managing menopausal symptoms.

Summary

Terms: menopause — 12 mo without a menstrual period after the final menstrual period (FMP); menopausal transition — variability in menstrual cycles before FMP; perimenopause — the onset of symptoms through 1 yr after the FMP

Natural history of menopause: the average age of menopause in the United States is 51.4 yr; predictors of age at menopause include genetics, family history, ethnicity (eg, Hispanic women have earlier menopause), smokers, and reproductive history (eg, women who have never had children or have shorter cycle length have earlier menopause)

Prevalence of menopausal symptoms: ≈80% of women experience hot flashes, ≈50% have night sweats, and 40% to 60% have sleep disturbances; vaginal dryness and changes in sexual function are other symptoms; it is unclear whether depression and mood changes, cognition changes, urinary complaints, and joint pain are related to menopause or age; menopausal symptoms are transitory; Politi et al (2008) — in a meta-analysis assessing the progression of symptoms, the percentage of women with symptoms increased in the 2 yr preceding the FMP, tended to peak 1 yr later, and did not return to premenopausal levels until ≈8 yr after FMP; 50% of women had symptoms 4 yr post-FMP, and 10% women had symptoms ≤12 yr; bothersome symptoms tend to peak at ≈2 yr post-FMP; ≈8% of women continue to have symptoms after 10 yr; Avis et al (2015) — in an observational study, >50% of women had frequent vasomotor symptoms that last 7.4 yr; the earlier symptoms started, the longer they were likely to last

Hormone therapy (HT): Manson et al (Women's Health Initiative; 2013) — studied the role of HT in chronic diseases prevention; women with an intact uterus received estrogen-progestin therapy (EPT) vs placebo, and women who had hysterectomy received estrogen therapy (ET) vs placebo; older women had increased risk for coronary heart disease; risk-benefit ratio of HT is most favorable when initiated in younger women; there was no difference in all-cause mortality between groups during or after intervention phase at 18 yr follow-up; ET was associated with less breast cancer (BC) risk, and EPT increased risk but evidence of BC mortality was not conclusive; Chlebowski et al (2020) — long-term follow-up study included women with no BC and a normal baseline mammogram; similar intervention groups; ET was associated with less BC risk and lower BC mortality; EPT increased BC risk but had no significant impact on BC mortality; age is the biggest risk factor for heart disease, BC, and other diseases except cervical cancer

American College of Obstetricians and Gynecologists: recommends systemic HT as the most effective treatment for menopausal symptoms; lower-dose therapy has a better adverse effect profile but may be less effective and take longer to work; risks include BC and thromboembolic disease (TED); recommend discussing the risks and benefits with women considering HT

Transdermal estrogen (TE): no hepatic first pass metabolism; data suggest lower risk for TED and stroke than oral estrogen; for menopausal women with systemic estrogen indications, TE might be a better option; for women with oral estrogen indications, estradiol might be better than conjugated equine estrogens (eg, Cenestin, Enjuvia, Premarin); women with uteruses must take progestin along with TE to lower risk for endometrial cancer; 1 mg micronized 17β-estradiol, 50 μg transdermal β-estradiol, 0.625 mg conjugated equine estrogen, and 1.25 mg piperazine estrone sulfate stop hot flashes in ≈80% of women

Low-dose estrogen: symptoms improve in 63% of women on low-dose estrogen compared with 83% on standard-dose estrogen; can start with a higher dose and taper down in women with severe symptoms; low-dose estrogen is associated with less bleeding and breast tenderness and may require less progestin

Progestins: micronized progesterone is considered more natural; can be taken as 200 mg daily for 12 days or 100 mg daily continuously; data on safety are limited; usually, cyclic therapy is considered before menopause to regulate periods, and continuous therapy after menopause; quarterly progestin is not recommended because of concern for increased endometrial proliferation; levonorgestrel-containing intrauterine device is often used off-label

Selective estrogen receptor modulators: tissue-selective estrogen complexes; conjugated equine estrogens (0.45 mg) and bazedoxifene (20 mg) combination (Duavee) is approved for the treatment of menopausal symptoms and osteoporosis prevention; has some agonist effect on bone and antagonist effect on uterine tissue; may relieve menopausal symptoms without increasing endometrial cancer or BC risk; reduces daily hot flashes vs placebo; similar incidence of TED; may be beneficial for women who cannot tolerate progesterone

Tapering: 25% of women who stop therapy have return of symptoms; there is conflicting evidence about benefits of tapering vs discontinuation; tapering can be done by daily dose, number of days per week, or strength of the TE; taper until mild symptoms appear and continue that dose until symptoms improve, then taper again

Medical management: paroxetine — a study showed significant reduction in hot flash score (62% in 12.5-mg group, 65% in 25-mg group, and 38% in placebo group); may interfere with cytochrome P450 system and decrease active metabolite in women taking tamoxifen; paroxetine salt (eg, Brisdelle, Paxil, Pexeva) is the first low-dose nonhormonal treatment approved by the US Food and Drug Administration (FDA) for menopausal symptoms; escitalopram — a selective serotonin reuptake inhibitor; reduces hot flash frequency by 55% vs 36% with placebo; venlafaxine — 61% vs 27% reduction compared with placebo; 150 mg is more effective than 75 mg; can start with 37.5 mg and gradually increase as needed; takes a few weeks to have an effect; desvenlafaxine (DVS) — a metabolite of venlafaxine; 64% vs 51% reduction in hot flashes at 12 wk; less severe hot flashes occurred with DVS; a study showed 100 and 150 mg of DVS were better than placebo at 12 wk, while the higher dose was better at 26 wk; off-label use; gabapentin — 45% reduction in hot flashes compared with placebo; 900 mg/day is more effective than placebo; may increase ability to sleep when taken at bedtime; clonidine — 0.1 mg transdermal patch is associated with 40% reduction in hot flashes; side effects can be limiting; oxybutynin — more effective than placebo; 5- to 10-mg dose is recommended; limited by side effects

The North American Menopause Society (NAMS) guidelines: recommend cognitive behavioral therapy and hypnosis; paroxetine is the only nonhormonal treatment approved by the US FDA; weight loss, mindfulness-based stress reduction, some soy dietary changes, and stellate ganglion block are recommended with caution; cooling techniques, avoidance of triggers, exercise, yoga, paced respiration, relaxation, over-the-counter supplements, and calibration of neural oscillations are not recommended; HT can prevent bone loss, but NAMS do not recommend prescribing it for women with osteoporosis; risk varies with age; younger women have lower risks; individualize treatment; monitor and reassess risks and benefits periodically; women <60 yr of age approaching menopause may benefit more; women >60 yr of age who start therapy 10 or 20 yr after menopause may be at higher risk

Vaginal atrophy: estrogen cream is effective and safer than pills; vaginal moisturizers help with moisturizing but do not build vaginal mucosa; there is no evidence to suggest vaginal rings are safer

Genitourinary syndrome: vaginal changes associated with dyspareunia; may have physical discomfort; high incidence; treatment — vaginal moisturizers are used several times a week; vaginal lubricants are used for sexual intercourse; local estrogen is most effective, can reduce the incidence of urinary tract infections and overactive bladder, and is used daily for a few weeks, then twice weekly; it is available as cream, tablets, and rings; use full applicator once weekly for 7 to 14 days, then half an applicator several times a week; ospemifene treats postmenopausal atrophy-related dyspareunia (hot flashes are the most common adverse effect); intravaginal dehydroepiandrosterone (prasterone) is a daily vaginal suppository (associated with an increase in circulating testosterone); laser or energy-based devices are not approved by US FDA; warnings include vaginal burns and dyspareunia; complementary therapies include oral vitamin D, vaginal vitamin E, and oral and vaginal probiotics; recommendation — education followed by lubricants and vaginal moisturizers; consider other treatment options; consult an oncologist for treating women with breast and endometrial cancer

Readings

Avis NE, Crawford SL, Greendale G, et al. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med. 2015;175(4):531-539. doi:10.1001/jamainternmed.2014.8063. View Article; Chlebowski RT, Anderson GL, Aragaki AK, et al. Association of menopausal hormone therapy with breast cancer incidence and mortality during long-term follow-up of the Women's Health Initiative randomized clinical trials. JAMA. 2020;324(4):369-380. doi:10.1001/jama.2020.9482. View Article; Liu JH. Selective estrogen receptor modulators (SERMS): keys to understanding their function. Menopause. 2020 October;27(10):1171–1176. DOI: 10.1097/GME.0000000000001585. View Article; Liu JH. The role of progestogens in menopausal hormone therapy. Clinical Obstetrics & Gynecology. 2021 December;64(4):772–783. DOI: 10.1097/GRF.0000000000000657. View Article; 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. The Journal of the American Medical Association. 2013 October 2;310(13):1353–1368. DOI: 10.1001/JAMA.2013.278040. View Article; NAMS position statement. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022 July;29(7):767–794. DOI: 10.1097/GME.0000000000002028. View Article; Politi MC, Schleinitz MD, Col NF. Revisiting the duration of vasomotor symptoms of menopause: a meta-analysis. J Gen Intern Med. 2008;23(9):1507-1513. doi:10.1007/s11606-008-0655-4. View Article; Pinkerton JV, Joffe H, Kazempour K, et al. Low-dose paroxetine (7.5 mg) improves sleep in women with vasomotor symptoms associated with menopause. Menopause. 2015 January;22(1):50–58. DOI: 10.1097/GME.0000000000000311. View Article; Voedisch AJ, Dunsmoor-Su R, Kasirsky J. Menopause: A global perspective and clinical guide for practice. Clinical Obstetrics & Gynecology. 2021 September;64(3):528–554. DOI: 10.1097/GRF.0000000000000639. View Article.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose. Dr. Walsh's lecture includes information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Walsh was recorded at CME Primary Care Medicine: Principles and Practice 2022, held in San Francisco, CA, on October 19, 2022, and presented by the University of California, San Francisco, School of Medicine. For information on future CME activities from this presenter, please visit meded.ucsf.edu/continuing-education. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.25 CE contact hours.

Lecture ID:

FP710801

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.