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Hormone Therapy in Postmenopausal Persons: Primary Prevention of Chronic Conditions

Author/s: 
US Preventative Services task Force, Mangione, C. M., Barry, M. J., Nicholson, W. K., Cabana, M., Caughey, A. B., Chelmow, D., Coker, T. R., Davis, E. M., Donahue, K. E., Jaén, C. R., Kubik, M., Li, L., Ogedegbe, G., Pbert, L., Ruiz, J. M., Stevermer, J., Wong, J. B.

Importance: Menopause is defined as the cessation of a person's menstrual cycle. It is defined retrospectively, 12 months after the final menstrual period. Perimenopause, or the menopausal transition, is the few-year time period preceding a person's final menstrual period and is characterized by increasing menstrual cycle length variability and periods of amenorrhea, and often symptoms such as vasomotor dysfunction. The prevalence and incidence of most chronic diseases (eg, cardiovascular disease, cancer, osteoporosis, and fracture) increase with age, and US persons who reach menopause are expected on average to live more than another 30 years.

Objective: To update its 2017 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of systemic (ie, oral or transdermal) hormone therapy for the prevention of chronic conditions in postmenopausal persons and whether outcomes vary by age or by timing of intervention after menopause.

Population: Asymptomatic postmenopausal persons who are considering hormone therapy for the primary prevention of chronic medical conditions.

Evidence assessment: The USPSTF concludes with moderate certainty that the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons with an intact uterus has no net benefit. The USPSTF concludes with moderate certainty that the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy has no net benefit.

Recommendation: The USPSTF recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons. (D recommendation) The USPSTF recommends against the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy. (D recommendation).

Keywords 
Retrospective Studies postmenopause Chronic Disease hormone therapy Recommendation Statement

Compounded Bioidentical Hormone Therapy The National Academies Weigh In

Author/s: 
Stuenkel, Cynthia A., Manson, JoAnn E.

After 21 months of data collection and analysis, the NASEM committee’s overarching conclusion was, “Given the paucity of data on the safety and effectiveness of cBHT…there is insufficient evidence to support the overall clinical utility of cBHT as treatment for menopause.”1(p9) Specific concerns included inadequate labeling requirements of cBHT preparations, paucity of reliable pharmacokinetic and bioavailability data, technical challenges with difficult-to-compound steroid hormones (particularly pellet therapies), and insufficient high-quality evidence to establish whether cBHT preparations are safe and effective. The committee further concluded that most marketing claims about safety and effectiveness are not supported by evidence from welldesigned, properly controlled studies. Incomplete adverse event reporting contributes to safety concerns. The committee acknowledged that in the absence of safety and effectiveness data for cBHT, patient preference should not be the sole driver for use.

Keywords 
menopause hormone therapy Menopausal women

Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence

Author/s: 
Collaborative Group on Hormonal Factors in Breast Cancer

Summary

Background

Published findings on breast cancer risk associated with different types of menopausal hormone therapy (MHT) are inconsistent, with limited information on long-term effects. We bring together the epidemiological evidence, published and unpublished, on these associations, and review the relevant randomised evidence.

Methods

Principal analyses used individual participant data from all eligible prospective studies that had sought information on the type and timing of MHT use; the main analyses are of individuals with complete information on this. Studies were identified by searching many formal and informal sources regularly from Jan 1, 1992, to Jan 1, 2018. Current users were included up to 5 years (mean 1·4 years) after last-reported MHT use. Logistic regression yielded adjusted risk ratios (RRs) comparing particular groups of MHT users versus never users.

Findings

During prospective follow-up, 108 647 postmenopausal women developed breast cancer at mean age 65 years (SD 7); 55 575 (51%) had used MHT. Among women with complete information, mean MHT duration was 10 years (SD 6) in current users and 7 years (SD 6) in past users, and mean age was 50 years (SD 5) at menopause and 50 years (SD 6) at starting MHT. Every MHT type, except vaginal oestrogens, was associated with excess breast cancer risks, which increased steadily with duration of use and were greater for oestrogen-progestagen than oestrogen-only preparations. Among current users, these excess risks were definite even during years 1–4 (oestrogen-progestagen RR 1·60, 95% CI 1·52–1·69; oestrogen-only RR 1·17, 1·10–1·26), and were twice as great during years 5–14 (oestrogen-progestagen RR 2·08, 2·02–2·15; oestrogen-only RR 1·33, 1·28–1·37). The oestrogen-progestagen risks during years 5–14 were greater with daily than with less frequent progestagen use (RR 2·30, 2·21–2·40 vs 1·93, 1·84–2·01; heterogeneity p<0·0001). For a given preparation, the RRs during years 5–14 of current use were much greater for oestrogen-receptor-positive tumours than for oestrogen-receptor-negative tumours, were similar for women starting MHT at ages 40–44, 45–49, 50–54, and 55–59 years, and were attenuated by starting after age 60 years or by adiposity (with little risk from oestrogen-only MHT in women who were obese). After ceasing MHT, some excess risk persisted for more than 10 years; its magnitude depended on the duration of previous use, with little excess following less than 1 year of MHT use.

Interpretation

If these associations are largely causal, then for women of average weight in developed countries, 5 years of MHT, starting at age 50 years, would increase breast cancer incidence at ages 50–69 years by about one in every 50 users of oestrogen plus daily progestagen preparations; one in every 70 users of oestrogen plus intermittent progestagen preparations; and one in every 200 users of oestrogen-only preparations. The corresponding excesses from 10 years of MHT would be about twice as great.

Funding

Cancer Research UK and the Medical Research Council.

Keywords 
breast cancer postmenopause menopause estrogen hormone therapy

Menopausal Hormone Therapy

Author/s: 
Shifren, Jan L., Crandall, Carolyn J., Manson, JoAnn E.

Hormone therapy is the most effective treatment for managing menopausal vasomotor symptoms. Hot flashes and night sweats affect approximately 70% of midlife women and may persist for a decade or longer.1 Bothersome vasomotor symptoms have a significant adverse effect on sleep, daily functioning, and quality of life. Cognitive and mood symptoms often accompany disruptive hot flashes. Although lifestyle changes and nonhormonal options are available, women with frequent, severe vasomotor symptoms may greatly benefit from hormone therapy.2

Keywords 
hormone therapy menopause
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