Menopause and Hormone Therapy: The Science Explained

By Brian Opiyo, KRCHN, BScN | Institute of Human Physiology

Menopause is a normal biological transition, not a disease, yet it is poorly understood and often discussed through myths. In the UK, women can now expect to spend up to a third of their lives peri- or postmenopausal [1]. In November 2025, the U.S. Food and Drug Administration changed how hormone therapy for menopause is labelled, reopening a debate that has run for more than two decades. 

This article explains what happens in the body during menopause, what the evidence on hormone therapy shows, and where experts still disagree.

What menopause is

Menopause is better understood as a process than as a single event. Researchers describe it in stages, from the reproductive years, through the menopausal transition, to postmenopause, with the final menstrual period as the reference point [2]. The transition can last more than a decade and causes symptoms in a majority of women [3]. Menopause itself is defined in hindsight, as 12 consecutive months without a period, and the median age at natural menopause is about 50 [4].

The hormone control system

The symptoms of menopause make more sense once you know the system behind them. The brain and the ovaries are linked by a feedback loop. The hypothalamus releases a signal called GnRH, which prompts the pituitary gland to release two hormones, FSH and LH. These act on the ovaries, which grow follicles and make estradiol (the main estrogen) and progesterone. Those ovarian hormones then signal back to the brain and pituitary, which adjust the system up or down.

Each ovary starts life with a finite supply of follicles. Menopause reflects the depletion of those eggs and the resulting loss of ovarian hormones [3]. As the supply runs down, the ovaries respond less well to pituitary signals, and the pituitary releases more FSH to compensate. Rising FSH is one of the biological markers researchers use to stage the transition [2].

What makes menopause a whole-body event is that estrogen receptors are found in many tissues, including the brain, bone, blood vessels, and the urinary and genital tract. The resulting symptoms span temperature regulation, mood, thinking, and the genitourinary tract [3].

What changes in the body

Hot flashes and night sweats

Hot flashes are the best-known symptom. In most menopausal women, estrogen withdrawal produces hot flushes, which are a disorder of the hypothalamic temperature-control system [5]. One leading hypothesis points to KNDy neurons in the hypothalamus, named for three chemicals they release: kisspeptin, neurokinin B, and dynorphin. These neurons change markedly when estrogen falls, and they are thought to relay signals to the areas that trigger heat loss through skin vasodilation and sweating [5]. It remains a hypothesis rather than settled fact, and it is an active area of research. Night sweats can also interrupt sleep, which in turn affects mood and daytime function.

Bone

Bone is affected quietly. In the Study of Women's Health Across the Nation, which followed 1,902 women, bone mineral density changed little in early perimenopause but fell substantially in late perimenopause, by an average of about 0.018 g/cm² per year at the spine and 0.010 g/cm² per year at the hip. After menopause, the rates were about 0.022 and 0.013 g/cm² per year [6]. This accelerated loss is why menopause is an important window for thinking about osteoporosis.

Heart and blood vessels

An American Heart Association scientific statement reviews evidence that the transition is a period of accelerating cardiovascular risk. During midlife, women experience increases in LDL cholesterol, a higher risk of metabolic syndrome, and changes in blood vessel structure, which appear to be driven more by the menopause transition than by age alone. Earlier age at natural menopause is also a marker of higher cardiovascular risk [4].

Urinary and genital tissues

The tissues of the vagina, vulva, and lower urinary tract depend on estrogen. As levels fall, women can develop dryness, discomfort, and urinary changes, a group of symptoms now called the genitourinary syndrome of menopause [3].

Mood, sleep, and thinking

Many women report disrupted sleep, low mood, anxiety, and difficulty concentrating. Mood disruption and temporary cognitive difficulties are recognised features of the transition [3], but they have many contributors, including night sweats and life stressors. They should be assessed in context rather than automatically attributed to menopause.

Hormone therapy

What it is and what it does

Menopausal hormone therapy replaces some of the estrogen the ovaries no longer make. Women who still have a uterus also need a progestogen, because estrogen alone raises the risk of cancer of the uterine lining [7].

The North American Menopause Society's 2022 position statement describes hormone therapy as the most effective treatment for hot flashes and for the genitourinary symptoms of menopause, and notes that it prevents bone loss and fracture. It also stresses that the risks differ by type, dose, duration, route of administration, timing of initiation, and whether a progestogen is used [8].

Why it became controversial

Hormone therapy was once the norm for American women [7]. That changed in 2002, when the Women's Health Initiative stopped its estrogen-plus-progestin trial early. 

The trial had randomized 16,608 postmenopausal women aged 50 to 79 with a uterus to a daily pill containing conjugated equine estrogens (0.625 mg) and medroxyprogesterone acetate (2.5 mg), or to placebo. After an average of 5.2 years, the monitoring board recommended stopping because health risks exceeded benefits [9].

Compared with placebo, the hormone group had higher rates of coronary heart disease (hazard ratio 1.29), breast cancer (1.26), stroke (1.41), and pulmonary embolism (2.13), but lower rates of hip fracture (0.66) and colorectal cancer (0.63) [9]. 

In absolute terms, for every 10,000 women taking the pills for a year, that meant about 7 more heart events, 8 more strokes, 8 more pulmonary emboli, and 8 more breast cancers, against 5 fewer hip fractures and 6 fewer colorectal cancers [9]. Prescriptions then fell sharply, including among younger women with troublesome symptoms [7].

What the trial could not tell us

Later work stressed the limits of those results. The women studied had an average age of about 63, and the formulation tested is no longer commonly prescribed [10]. Risks also appear to depend on age: a reanalysis of the original data, reported by the Associated Press, found no increase in heart problems among women in their 50s taking estrogen-based drugs, but an increase among women in their 70s [7].

The 2022 NAMS statement reaches a similar conclusion. For healthy symptomatic women who are younger than 60 or within 10 years of menopause onset and have no contraindications, it judges the benefit-risk ratio favourable for bothersome hot flashes and prevention of bone loss. For those who start more than 10 years after onset or after age 60, the balance appears less favourable because of greater absolute risks of coronary heart disease, stroke, blood clots, and dementia [8].

What the FDA changed in November 2025

On 10 November 2025, the FDA announced that it would remove boxed warnings, its most serious type, from menopausal hormone therapy products. The warnings about cardiovascular disease, breast cancer, and probable dementia are being removed, while a warning about endometrial cancer remains for estrogen-only therapy [7,10]. The agency recommends starting systemic hormone therapy within 10 years of menopause onset or before age 60 [10,11].

A commentary in an obstetrics and gynaecology journal adds that the change moves towards product-specific labelling and drops the earlier advice to use the lowest dose for the shortest time [11]. The FDA also approved a new nonhormonal treatment for moderate to severe hot flashes, giving women another option [10].

Where experts still disagree

Supporters of the change, including the president of the American College of Obstetricians and Gynecologists, argue that the blanket warning created hesitancy and scared away women who could benefit [7]. The journal commentary calls the change a step towards individualised benefit-risk assessment and shared decision-making [11].

Critics raise two main concerns. The first is process: the FDA did not convene one of its standing advisory committees, and some experts said it should have [7]. The second is scope: JoAnn Manson of Harvard Medical School said the evidence for overall health benefits is not as conclusive as officials described [7].

The U.S. Preventive Services Task Force, in its 2022 recommendation, advised against using hormone therapy, whether estrogen alone or combined with progestin, to prevent chronic conditions in postmenopausal people. That recommendation does not apply to women using hormone therapy to manage symptoms such as hot flashes [12]. 

Public Citizen, a consumer advocacy group, criticized FDA officials for appearing to promote hormone therapy for uses it is not approved for, such as preventing cardiovascular disease and cognitive decline [13]. FDA-approved indications remain limited to treating menopausal symptoms and preventing postmenopausal osteoporosis [12].

The practical middle ground is individualisation. Hormone therapy is well supported for bothersome symptoms in appropriately selected women, particularly those who start relatively early, but it is not a general anti-ageing or disease-prevention treatment [8,12]. Note also that the FDA decision applies to U.S. labelling. Other countries' regulators and national guidelines may differ, and the products available to you depend on where you live.

Common myths, corrected

Myth: Menopause is a disease that needs treatment. It is a normal transition. Treatment is for symptoms that affect quality of life, or for specific risks such as bone loss, not for menopause itself [3].

Myth: Hormone therapy is either dangerous or a miracle. Neither is accurate. Benefits and risks depend on age, time since menopause, dose, route, and personal medical history [8,11].

Myth: Hot flashes are just an inconvenience. They can disrupt sleep and daily life, and in some studies they are associated with worse cardiovascular risk factor levels [4], which is a legitimate reason to seek advice.

Myth: Hormones are the only thing that helps. A nonhormonal medicine for hot flashes has now been approved [10], and lifestyle measures matter for long-term bone and heart health.

Myth: Menopause only affects reproduction. Estrogen receptors in the brain, bone, blood vessels, and urinary tract mean the effects are body-wide [3,4,6].

Nutrition and lifestyle through the transition

Food and exercise do not replace medical treatment, but they support the tissues most affected by falling estrogen. The American Heart Association statement describes lifestyle and behavioural interventions as critical to maintaining cardiovascular health through this stage [4]. The habits below are commonly recommended in clinical practice, and individual advice should come from your doctor or dietitian.

• Protect bone: Get enough calcium and vitamin D, and do weight-bearing and resistance exercise.
• Protect muscle: Include enough protein at each meal, because muscle mass declines with age.
• Protect the heart: Favour vegetables, legumes, whole grains, and unsaturated fats, and keep physically active.
• Avoid smoking and limit alcohol, which affect bone and heart health.
• Prioritise sleep, including a cool bedroom, since night sweats are a common cause of poor sleep.

Questions to ask your doctor

• Are my symptoms due to menopause, or could something else be contributing?
• Is hormone therapy suitable for me, given my age, time since my last period, and personal and family history?
• If so, which form and route is best, and how often should we review it?
• What nonhormonal options are available if I cannot or prefer not to take hormones?
• Should I have my bone health and cardiovascular risk checked?

Key takeaways

• Menopause results from the depletion of ovarian follicles and loss of ovarian hormones, and it affects many body systems, not only the reproductive tract [3].
• Bone loss and cardiovascular risk both accelerate around the transition [4,6].
• The 2002 trial findings were real, but later analysis shows risks vary by age, timing, and formulation [8,10].
• In November 2025, the FDA removed several boxed warnings and advised starting hormone therapy within 10 years of menopause or before age 60 [10,11].
• Experts still disagree about wider claimed benefits, so treatment should be individualised and discussed with a clinician [7,12].

Disclaimer

This article is for educational purposes only and is not medical advice. Menopause care is individual, and decisions about hormone therapy or any other treatment should be made with a qualified healthcare professional.

About the author

Brian Opiyo (KRCHN, BScN) is a Medical Data Analyst in Life and Medical Insurance with over seven years of experience spanning nursing practice, quality assurance, insurance, and healthcare provider management. He runs the Institute of Human Physiology, a channel and blog that explains human physiology, nutrition, and general medicine, and Healthcare X, a channel covering healthcare financing, life and medical insurance, and healthcare data management systems. 

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