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Medical Management of Menopausal Symptoms

Author: Kathryn I. Marko, MD, NCMP, FACOG

Mentor: Nancy D. Gaba, MD, FACOG
Editor: Peter F. Schnatz, DO

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Menopausal symptoms vary for each woman. Symptoms can arise in the perimenopausal period and last throughout the rest of a woman’s lifetime.

Vasomotor symptoms occur in 75 to 80% of women undergoing menopause. The most effective treatment is systemic hormone therapy (HT) which includes Estrogen and Progestogen Therapy (EPT) or Estrogen alone Therapy (ET). Estrogen can be given orally, transvaginally or transdermally. If a woman has a uterus, a progestin or bazedoxifene (a selective estrogen receptor modulator) must be added for endometrial protection. There are benefits to HT beyond symptom reduction, including reduced risk of fractures, colon cancer, and type 2 diabetes mellitus. Women who initiate HT between the ages of 50 and 59 years and who are less than 10 years from menopause onset may have a reduced risk of cardiovascular disease. In this population of women, conjugated equine estrogen (CEE) alone decreases the risk of breast cancer. However, HT is not FDA approved for primary prevention.HT increases the risk of venous thromboembolism and EPT used for greater than 5 years may increase the risk of breast cancer. Venous thromboembolism risk (18 additional cases per 10,000 women-years) can be reduced by administering transdermal estrogen. Breast cancer risk (1 additional case per 1,000 women) is increased with EPT but not with ET. In most symptomatic women aged 50 to 59 years, the overall benefits of HT outweigh the risks.

HT should be individualized. Women should receive the appropriate dosage, via the appropriate route, for the appropriate duration of time to achieve their treatment goals. HT should not be automatically stopped at age 65 years. The decision of whether to discontinue HT should consider the benefits and risks as women age. HT can be stopped without tapering. If symptoms resume, HT can be restarted or a taper can be attempted. Custom compounded bioidentical HT should be avoided without a good indication, such as an allergy or digestive disorder, as  dosing and purity are uncertain and risk profiles appear to be elevated. Furthermore, due to safety concerns, pellet therapy should not be used for standard menopausal symptoms.  

Nonhormonal medical therapies for vasomotor symptoms include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), gabapentin, clonidine, and the newer pharmacotechnology aimed at the hypothalamic KNDy neurons. The neurokinin B antagonist, fezolinetant, is currently the only such medication available. Hence, Paroxetine and Fezolinetant are the only FDA-approved nonhormonal therapies. Paroxetine may affect the metabolism of tamoxifen and should not be used in women taking this medication. Lifestyle modifications, phytoestrogens, and herbal remedies lack proven efficacy.  

Genitourinary syndrome of menopause (GSM) occurs in 10-40% of women and includes vaginal dryness and dyspareunia. All systemic HT options are effective in treating GSM. However, local therapy is first line if there are no systemic symptoms. Low-dose local/topical ET, in cream, tablet, or ring preparations, has minimal systemic absorption and a progestin is not required for endometrial protection. Prasterone, synthetic dehydroepiandrosterone, is a daily vaginal suppository to treat dyspareunia and it elevates serum estrone levels. Ospemifene, an oral selective estrogen receptor modulator, improves vaginal symptoms with no endometrial activity. Nonhormonal therapies for GSM include moisturizers and lubricants. Vaginal laser therapies have safety concerns, do not have long-term safety or efficacy data, and lack FDA approval for this indication. Hence, laser therapy should not be recommended for the treatment of GSM.

Further Reading:

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 Jul 28;324(4):369-380. doi: 10.1001/jama.2020.9482. PMID: 32721007; PMCID: PMC7388026.

“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. 2022 Jul 1;29(7):767-794. doi: 10.1097/GME.0000000000002028. PMID: 35797481.

“The 2023 Nonhormone Therapy Position Statement of The North American Menopause Society” Advisory Panel. The 2023 nonhormone therapy position statement of The North American Menopause Society. Menopause. 2023 Jun 1;30(6):573-590. doi: 10.1097/GME.0000000000002200. PMID: 37252752.

Jiang X, Bossert A, Parthasarathy KN, et al. Safety assessment of compounded non-FDA-approved hormonal therapy versus FDA-approved hormonal therapy in treating postmenopausal women. Menopause. 2021 May 10;28(8):867-874. doi: 10.1097/GME.0000000000001782. PMID: 33973545.

Initial Publication: November 2020, Revised May 2022, Revised March 2024.


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