Postmenopausal Hormone Therapy—Local and Systemic: A Pharmacologic Perspective

Posted on December 14, 2020

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Source: The Journal of Clinical Pharmacology
Taryn Smith MD, NCMP Sabrina Sahni MD, NCMP Holly L. Thacker MD, FACP, CCD, NCMP
Abstract
Every woman, if she lives long enough, will transition into menopause, and as the US population ages, women will be spending more time in a postmenopausal state than before. For postmenopausal women, the decision to initiate menopausal hormone therapy should be individualized. A thorough evaluation of the patient's cardiovascular, venous thromboembolic, cancer, and fracture risk should be considered along with the woman's quality of life. Hormone therapy exerts its therapeutic effects on vasomotor symptoms, the skeleton, and the genitourinary system independent of age since menopause and these benefits are lost once hormone therapy is stopped. Here we review the pharmacologic properties dose, formulation, mode of administration, timing of initiation, and duration of hormonal therapies in regard to optimizing benefit and minimizing risk to the patient. This discussion will focus on the effects of common hormonal therapies including estrogen (local and systemic), progesterone, estrogen receptor agonist/antagonist, and local dehydroepiandrosterone and include a brief review of compounded bioidentical hormone therapy.

Every woman, if she lives long enough, will transition into menopause. According to the North American Menopause Society (NAMS), roughly 6000 US women transition to menopause each day. It has been estimated that >50 million women will be postmenopausal in 2020,1 and as the US population ages, women will be spending more time in a postmenopausal state than before. In addition to bothersome vasomotor symptoms, postmenopausal women are at greater risk for genitourinary and sexual dysfunction, cognitive decline, cardiovascular disease, and significant bone loss.2 Hormone therapy has repeatedly been shown to be the most effective treatment for problematic vasomotor symptoms of menopause while significantly decreasing the risk of postmenopausal bone loss.3 However, following the Women's Health Initiative (WHI) trials, many questions regarding the safety of hormone therapy have arisen. The WHI trials were conducted to evaluate the risks and benefits of hormone therapy taken for primary prevention of chronic diseases among postmenopausal woman, whose average age was 63 years.4 Women were stratified to either combined conjugated equine estrogen 0.625 mg plus medroxyprogesterone acetate (MPA) 2.5 mg if they had a uterus and conjugated equine estrogen alone if they had had a hysterectomy. The conjugated equine estrogen plus MPA arm was terminated after 5.6 years because of increased risk of breast cancer, whereas the conjugated equine estrogen‐only arm was terminated after 7.2 years because of increased stroke risk.4

The results of the WHI trials cannot be applied to other hormone regimens, as each arm of the trials evaluated a single dose and formulation of orally administered hormone therapy. Since the publication of the WHI trials, experts have investigated how hormone therapy formulation, timing of administration, mode of hormone therapy delivery, and combination of hormones used impacts a woman's risk. New data have improved expert understanding, allowing for individualized hormone therapy regimens that optimally balance risk and benefit. This article reviews the available data regarding conventional and newer options for systemic and local hormone therapies.

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