Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause.[1][2] Effects of menopause can include symptoms such as hot flashes, accelerated skin aging, vaginal dryness, decreased muscle mass, and complications such as osteoporosis (bone loss), sexual dysfunction, and vaginal atrophy. They are mostly caused by low levels of female sex hormones (e.g. estrogens) that occur during menopause.[1][2]
Estrogens and progestogens are the main hormone drugs used in HRT. Progesterone is the main female sex hormone that occurs naturally and is also manufactured into a drug that is used in menopausal hormone therapy.[1] Although both classes of hormones can have symptomatic benefit, progestogen is specifically added to estrogen regimens, unless the uterus has been removed, to avoid the increased risk of endometrial cancer. Unopposed estrogen therapy promotes endometrial hyperplasia and increases the risk of cancer, while progestogen reduces this risk.[3][4] Androgens like testosterone are sometimes used as well.[5] HRT is available through a variety of different routes.[1][2]
The long-term effects of HRT on most organ systems vary by age and time since the last physiological exposure to hormones, and there can be large differences in individual regimens, factors which have made analyzing effects difficult.[6] The Women’s Health Initiative (WHI) is an ongoing study of over 27,000 women that began in 1991, with the most recent analyses suggesting that, when initiated within 10 years of menopause, HRT reduces all-cause mortality and risks of coronary disease, osteoporosis, and dementia; after 10 years the beneficial effects on mortality and coronary heart disease are no longer apparent, though there are decreased risks of hip and vertebral fractures and an increased risk of venous thromboembolism when taken orally.[7][8]
“Bioidentical” hormone replacement is a development in the 21st century and uses manufactured compounds with “exactly the same chemical and molecular structure as hormones that are produced in the human body.”[9] These are mainly manufactured from plant steroids[10] and can be a component of either registered pharmaceutical or custom-made compounded preparations, with the latter generally not recommended by regulatory bodies due to their lack of standardization and formal oversight.[11] Bioidentical hormone replacement has inadequate clinical research to determine its safety and efficacy as of 2017.[12]
The current indications for use from the United States Food and Drug Administration (FDA) include short-term treatment of menopausal symptoms, such as vasomotor hot flashes or vaginal atrophy, and prevention of osteoporosis.[13]
Medical uses
Approved uses of HRT in the United States include short-term treatment of menopausal symptoms such as hot flashes and vaginal atrophy, and prevention of osteoporosis.[13] The American College of Obstetrics and Gynecology (ACOG) approves of HRT for symptomatic relief of menopausal symptoms,[14] and advocates its use beyond the age of 65 in appropriate scenarios.[15] The 2016 annual meeting of The Menopause Society (formerly the North American Menopause Society) mentioned that HRT may have more benefits than risks in women before the age of 60.[16]
A consensus expert opinion published by The Endocrine Society stated that when taken during perimenopause or the initial years of menopause, HRT carries fewer risks than previously published, and reduces all cause mortality in most scenarios.[2] The American Association of Clinical Endocrinologists (AACE) has also released position statements approving of HRT when appropriate.[12]
Women receiving this treatment are usually post-, peri-, or surgically induced menopausal. Menopause is the permanent cessation of menstruation resulting from loss of ovarian follicular activity, defined as beginning twelve months after the final natural menstrual cycle. This twelve month time point divides menopause into early and late transition periods known as ‘perimenopause’ and ‘postmenopause’.[4] Premature menopause can occur if the ovaries are surgically removed, as can be done to treat ovarian or uterine cancer.
Demographically, the vast majority of data available is in postmenopausal American women with concurrent pre-existing conditions and an average age of over 60 years.[17]
Menopausal symptoms
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HRT is often given as a short-term relief from menopausal symptoms during perimenopause.[18] Potential menopausal symptoms include:[1][2]
- Hot flashes – vasomotor symptoms
- Vulvovaginal atrophy – atrophic vaginitis and dryness
- Dyspareunia – painful sexual intercourse due to vaginal atrophy and lack of lubrication
- Bone loss – decreased bone mineral density, which can eventually lead to osteopenia, osteoporosis, and associated fractures
- Decreased sexual desire
- Defeminization – diminished feminine fat distribution and accelerated skin aging[19][20]
- Sleep disturbances and joint pain
The most common of these are loss of sexual drive and vaginal dryness.[4][21]
The use of hormone therapy for heart health among menopausal women has declined significantly over the past few decades.[22] In 1999, nearly 27% of menopausal women in the U.S. used estrogen, but by 2020, that figure had dropped to less than 5%.[23][24] Recent evidence in 2024 suggests evidence supporting the cardiovascular benefits of hormone therapy, including improvements in insulin resistance and other heart-related markers.[25] This adds to a growing body of research highlighting hormone therapy’s effectiveness, not only for heart health but also for managing menopausal symptoms like hot flashes, disrupted sleep, vaginal dryness, and painful intercourse.[26] Despite its proven benefits, many menopausal women avoid hormone therapy, often due to lingering misconceptions about its risks and societal discomfort with openly discussing menopause.[22]
Sexual function
HRT can help with the lack of sexual desire and sexual dysfunction that can occur with menopause. Epidemiological surveys of women between 40 and 69 years suggest that 75% of women remain sexually active after menopause.[4] With increasing life spans, women today are living one third or more of their lives in a postmenopausal state, a period during which healthy sexuality can be integral to their quality of life.[27]
Decreased libido and sexual dysfunction are common issues in postmenopausal women, an entity referred to hypoactive sexual desire disorder (HSDD); its signs and symptoms can both be improved by HRT.[5][28] Several hormonal changes take place during this period, including a decrease in estrogen and an increase in follicle-stimulating hormone. For most women, the majority of change occurs during the late perimenopausal and postmenopausal stages.[4] Decreases in sex hormone-binding globulin (SHBG) and inhibin (A and B) also occur. Testosterone is present in women at a lower level than men, peaking at age 30 and declining gradually with age; there is less variation during the menopausal transition relative to estrogen and progesterone.[4]
A global consensus position statement has advised that postmenopausal testosterone replacement to premenopausal levels can be effective for HSDD. Safety information for testosterone treatment is not available beyond two years of continuous therapy however and dosing above physiologic levels is not advised.[29] Testosterone patches have been found to restore sexual desire in post menopausal women.[30] There is insufficient data to evaluate the impact of testosterone replacement on heart disease, breast cancer, with most trials having included women taking concomitant estrogen and progesterone and with testosterone therapy itself being relatively short in duration. In the setting of this limited data, testosterone therapy has not been associated with adverse events.[29]
Not all women are responsive, especially those with preexisting sexual difficulties.[21] Estrogen replacement can restore vaginal cells, pH levels, and blood flow to the vagina, all of which tend to deteriorate at the onset of menopause. Pain or discomfort with sex appears to be the most responsive component to estrogen.[21] It also has been shown to have positive effects on the urinary tract.[21] Estrogen can also reduce vaginal atrophy and increase sexual arousal, frequency and orgasm.[21]
The effectiveness of hormone replacement can decline in some women after long-term use.[21] A number of studies have also found that the combined effects of estrogen/androgen replacement therapy can increase libido and arousal over estrogen alone.[21] Tibolone, a synthetic steroid with estrogenic, androgenic, and progestogenic properties that is available in Europe, has the ability to improve mood, libido, and physical symptomatology. In various placebo-controlled studies, improvements in vasomotor symptoms, emotional response, sleep disturbances, physical symptoms, and sexual desire have been seen, though it also carries a similar risk profile to conventional HRT.[5]
Muscle and bone
There is a significant decrease in hip fracture risk during treatment that to a lesser degree persists after HRT is stopped.[31][32] It also helps collagen formation, which in turn improves intervertebral disc and bone strength.[33]
Hormone replacement therapy in the form of estrogen and androgen can be effective at reversing the effects of aging on muscle.[34] Lower testosterone is associated with lower bone density and higher free testosterone is associated with lower hip fracture rates in older women.[35] Testosterone therapy, which can be used for decreased sexual function, can also increase bone mineral density and muscle mass.[29]