Hormone therapy in the postmenopausal years: considering benefits and risks in clinical practice

Abstract

BACKGROUND Menopausal symptoms can be very distressing and considerably affect a woman’s personal and social life. It is becoming more and more evident that leaving bothersome symptoms untreated in midlife may lead to altered quality of life, reduced work productivity and, possibly, overall impaired health. Hormone therapy (HT) for the relief of menopausal symptoms has been the object of much controversy over the past two decades. At the beginning of the century, a shadow was cast on the use of HT owing to the concern for cardiovascular and cerebrovascular risks, and breast cancer, arising following publication of a large randomized placebo-controlled trial. Findings of a subanalysis of the trial data and extended follow-up studies, along with other more modern clinical trials and observational studies, have provided new evidence on the effects of HT. OBJECTIVE AND RATIONALE The goal of the following paper is to appraise the most significant clinical literature on the effects of hormones in postmenopausal women, and to report the benefits and risks of HT for the relief of menopausal symptoms. SEARCH METHODS A Pubmed search of clinical trials was performed using the following terms: estrogens, progestogens, bazedoxifene, tibolone, selective estrogen receptor modulators, tissue-selective estrogen complex, androgens, and menopause. OUTCOMES HT is an effective treatment for bothersome menopausal vasomotor symptoms, genitourinary syndrome, and prevention of osteoporotic fractures. Women should be made aware that there is a small increased risk of stroke that tends to persist over the years as well as breast cancer risk with long-term estrogen–progestin use. However, healthy women who begin HT soon after menopause will probably earn more benefit than harm from the treatment. HT can improve bothersome symptoms, all the while conferring offset benefits such as cardiovascular risk reduction, an increase in bone mineral density and a reduction in bone fracture risk. Moreover, a decrease in colorectal cancer risk is obtainable in women treated with estrogen–progestin therapy, and an overall but nonsignificant reduction in mortality has been observed in women treated with conjugated equine estrogens alone or combined with estrogen–progestin therapy. Where possible, transdermal routes of HT administration should be preferred as they have the least impact on coagulation. With combined treatment, natural progesterone should be favored as it is devoid of the antiapoptotic properties of other progestogens on breast cells. When beginning HT, low doses should be used and increased gradually until effective control of symptoms is achieved. Unless contraindications develop, patients may choose to continue HT as long as the benefits outweigh the risks. Regular reassessment of the woman’s health status is mandatory. Women with premature menopause who begin HT before 50 years of age seem to have the most significant advantage in terms of longevity. WIDER IMPLICATIONS In women with bothersome menopausal symptoms, HT should be considered one of the mainstays of treatment. Clinical practitioners should tailor HT based on patient history, physical characteristics, and current health status so that benefits outweigh the risks.

Genetic, Molecular, and Cellular Determinants of Sex-Specific Cardiovascular Traits

“…76,77 Recent data suggest that the hormone therapy slightly increases a risk of stroke and a risk tends to persist over the years. 78 The role of testosterone in stroke is controversial. Several studies have suggested that androgens predispose young males to stroke.…”

Neuroendocrine Changes during Menopausal Transition

“…Women should be made aware that there is a small increased risk of stroke and breast cancer with long-term estrogen-progestin use. However, early treatment initiators will probably gain more profit than harm by improving bothersome symptoms, while obtaining offset benefits like cardiovascular risk reduction, increase in bone mineral density and reduction in bone fracture risk, decrease in colorectal cancer risk and in overall mortality [62].…”

Hormonal Approach for Postmenopausal Vulvovaginal Atrophy

“…Low-dose vaginal ET is the most used pharmacological treatment for VVA, being also the most effective and safer option. During the low-dose vaginal ET use, systemic estrogen absorption is minimal, and serum estradiol remains within postmenopausal levels (7)(8)(9)(10)(11)(12)(13)(14).…”

“…The use of a progestogen is not required for endometrial protection in women receiving low-dose vaginal ET. Nonetheless, periodic endometrial surveillance or progestogen use can be considered for women at high-risk endometrial neoplasia (7)(8)(9)(10)(11)(12)(13)(14).…”

“…Another complication that usually not requires treatment is the development of mild transient candidiasis (19). Vaginal ET does not seem to increase the risk of venous thromboembolism, but data on high-risk patients are lacking (7)(8)(9)(10)(11)(12)(13)(14). Essentially, non-hormonal treatments are preferred initial strategies for the survivors of hormone-dependent cancers (breast and endometrial cancers).…”