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. 

References.

1. Menopause: physiology, definitions, and symptoms. Best Pract Res Clin Endocrinol Metab. 2024;38(1):101855. doi:10.1016/j.beem.2023.101855
2. Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, et al. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. Menopause. 2012;19(4):387-395. doi:10.1097/gme.0b013e31824d8f40
3. Santoro N, Roeca C, Peters BA, Neal-Perry G. The menopause transition: signs, symptoms, and management options. J Clin Endocrinol Metab. 2021;106(1):1-15. doi:10.1210/clinem/dgaa764
4. El Khoudary SR, Aggarwal B, Beckie TM, Hodis HN, Johnson AE, Langer RD, et al. Menopause transition and cardiovascular disease risk: implications for timing of early prevention: a scientific statement from the American Heart Association. Circulation. 2020;142(25):e506-e532. doi:10.1161/CIR.0000000000000912
5. Rance NE, Dacks PA, Mittelman-Smith MA, Romanovsky AA, Krajewski-Hall SJ. Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: a novel hypothesis on the mechanism of hot flushes. Front Neuroendocrinol. 2013;34(3):211-227. Available from: PMC3833827
6. Finkelstein JS, Brockwell SE, Mehta V, et al. Bone mineral density changes during the menopause transition in a multiethnic cohort of women. J Clin Endocrinol Metab. 2008;93(3):861-868. doi:10.1210/jc.2007-1876
7. Associated Press. FDA removes long-standing warning from hormone-based menopause drugs. 10 Nov 2025. Available from: abc7news.com
8. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022;29(7):767-794. doi:10.1097/GME.0000000000002028
9. Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288(3):321-333. doi:10.1001/jama.288.3.321
10. Becker's Hospital Review. FDA to remove boxed warnings from hormone therapy for menopause. Available from: beckershospitalreview.com
11. Elimination of the black box warning on menopausal hormone therapy. Obstet Gynecol. 2026;147(5):642-646. doi:10.1097/AOG.0000000000006226
12. US Preventive Services Task Force; Mangione CM, Barry MJ, Nicholson WK, et al. Hormone therapy for the primary prevention of chronic conditions in postmenopausal persons: US Preventive Services Task Force recommendation statement. JAMA. 2022;328(17):1740-1746. doi:10.1001/jama.2022.18625
13. ConsumerAffairs. FDA removes black box warning from menopause hormone therapy. 11 Nov 2025. Available from: consumeraffairs.com

How GLP-1 Drugs Work in the Body: A Physiology Guide- Ozempic, Wegovy.

 

How GLP-1 Drugs Work in the Body: A Physiology Guide

By the Institute of Human Physiology

GLP-1 medications such as semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) are among the most talked-about drugs in the world. Most coverage focuses on weight loss. This post looks at something different: what these drugs actually do inside your body, and why that explains both their benefits and their side effects.

First, what is GLP-1?

GLP-1 stands for glucagon-like peptide-1. It is a hormone your body already makes. Specialised cells in your small intestine, called L-cells, release it within minutes of eating, especially after meals containing carbohydrates and fats [1,2].

Think of GLP-1 as a message from your gut to the rest of your body: food has arrived, get ready to handle it.

There is one problem. Natural GLP-1 is broken down by an enzyme called DPP-4 in about two minutes [1,2]. Its signal is powerful but extremely short-lived.

The incretin effect: why a gut hormone matters

Physiologists noticed decades ago that glucose swallowed by mouth triggers a much larger insulin response than the same amount of glucose given directly into a vein. The extra response is called the incretin effect, and it comes from hormones released by the gut, mainly GLP-1 and GIP [1,2].

In people with type 2 diabetes, this gut-to-pancreas signal is weakened. The pancreas, however, can still respond when GLP-1 is supplied at pharmacological levels [1,2]. That is the physiological logic behind the drugs: they restore and amplify a signal the body already uses, rather than introducing something foreign to it.

This also explains why the same hormone appears in discussions of both diabetes and obesity. The gut, pancreas, liver, and brain all listen to it.

What the drugs change

GLP-1 medications are engineered versions of this hormone. They keep the same message but resist breakdown, so they act for much longer. Semaglutide, for example, lasts long enough to be taken once a week [3].

Tirzepatide goes one step further. It activates the GLP-1 receptor and also the receptor for a second gut hormone, GIP, which is why it is called a dual agonist [4].

Four things GLP-1 does in the body

1. It helps the pancreas release insulin, but only when needed

When blood glucose rises, GLP-1 signals the pancreatic beta cells to release more insulin. The effect is glucose-dependent: as blood sugar falls toward normal, the stimulus fades [1,2]. This is a major reason these drugs carry a lower risk of severe low blood sugar than some older diabetes medicines when used on their own.

2. It turns down glucagon

Glucagon is the hormone that tells the liver to release stored glucose. GLP-1 suppresses it after meals, which reduces the amount of sugar entering the blood from the liver [1,2].

3. It slows gastric emptying thereby reducing the amount of sugar entering the bloodstream

GLP-1 slows the rate at which food leaves the stomach. Food passes into the intestine more gradually, so blood sugar rises more slowly after a meal and you feel full for longer [1,2]. This is also the main source of side effects such as nausea, bloating, and constipation.

4. It acts on the brain's appetite centers

GLP-1 receptors are found in the hypothalamus and brainstem, areas that regulate hunger and fullness. Activating them reduces appetite and food cravings. Many people describe less "food noise," meaning fewer constant thoughts about eating. This brain effect is a large part of why the drugs work for weight loss, not just stomach emptying [1,2].

Why side effects happen

The most common side effects are nausea, vomiting, diarrhoea, and constipation [3]. They follow directly from the physiology above: a slower-moving gut and a changed appetite signal. They are usually worst when starting or increasing the dose, which is why doses are raised gradually.

More serious but less common concerns include gallbladder problems and pancreatitis [3,5]. Anyone with persistent severe abdominal pain should seek medical care promptly.

The muscle question

When people lose weight by any method, some of the loss is lean mass (muscle and other non-fat tissue), not only fat. This also happens with GLP-1 drugs [6]. Reported lean-mass losses vary between trials, and lean mass includes organs, bone, and water as well as muscle, so it is an imperfect stand-in for muscle [6]. Because appetite drops sharply, it becomes easy to eat too little protein.

Practical points that clinicians commonly discuss:

• Prioritise adequate protein at each meal.
• Include resistance training (weights or bodyweight exercise) to give muscles a reason to stay.
• Do not aim for the fastest possible weight loss at the cost of nutrition.

Specific protein targets should be personalised with a doctor or dietitian, especially for older adults and people with kidney disease.

What happens when you stop?

GLP-1 drugs do not reset the body's appetite and weight regulation. They work while they are in your system. In the STEP 1 trial extension, participants who had lost an average of 17.3% of body weight on semaglutide 2.4 mg regained about two-thirds of it within a year of stopping, and improvements in blood pressure, cholesterol, and blood sugar largely reverted toward baseline [7].

This is why many specialists now view obesity and type 2 diabetes as chronic conditions that may need long-term management, rather than something a short course "fixes." Whether and how to stop is a decision to make with your healthcare provider.

Beyond weight loss

Research into GLP-1 drugs is expanding. Large trials have shown cardiovascular benefits in some high-risk groups, including adults with obesity and existing heart disease but no diabetes [8], and studies are examining effects on kidney disease, fatty liver disease, and sleep apnoea. Because findings are still evolving, it is worth checking recent guidelines rather than relying on social media claims.

Common myths, corrected

Myth: "They are just appetite suppressants." Appetite is only one part of the picture. GLP-1 also acts on the pancreas, the liver's glucose output, and stomach emptying, as described above [1,2].

Myth: "They work without any change in eating or activity." In the STEP 1 trial, semaglutide was given as an adjunct to lifestyle intervention, not instead of it [7]. Protein intake and resistance training are also the main strategies discussed for protecting muscle [6].

Myth: "All the weight lost is fat." Some of it is lean mass, and how much varies between trials and between people [6].

Myth: "Once you reach your goal weight, you can simply stop." The trial evidence on stopping suggests much of the weight and many of the metabolic improvements return [7]. Any decision to stop should be planned with a clinician.

Eating well on a GLP-1 medication

Because the stomach empties more slowly and appetite is lower, some everyday habits are commonly suggested in clinical practice. They follow from the physiology above, and individual advice varies, so a dietitian or doctor should tailor them to you.

• Eat smaller, more frequent meals and stop when comfortably full, since a slower-emptying stomach fills up sooner.
• Put protein first at each meal, so a smaller appetite does not mean too little protein.
• Go easy on very fatty or fried foods. Fat already slows gastric emptying, and heavy meals can make nausea worse.
• Add fiber gradually from vegetables, legumes, and whole grains, and drink enough fluid to help with constipation.
• Keep moving, including some resistance exercise, to give muscles a reason to stay.

Questions to ask your doctor

• Is a GLP-1 medication appropriate for my health condition and other medicines?
• What side effects should I expect, and which ones need urgent attention?
• How much protein and what kind of exercise suit me?
• How will my progress be monitored, including body composition and not just weight?
• What is the plan if I want to stop or change the dose?

Key takeaways

• GLP-1 is a natural gut hormone; the drugs are long-acting versions of it.
• They lower blood sugar, slow stomach emptying, and reduce appetite through both the gut and the brain.
• Side effects mostly come from the same mechanisms that make the drugs work.
• Protein intake and strength training matter for protecting muscle.
• Stopping the medication often leads to weight regain, so planning with a clinician matters.

Disclaimer

This article is for educational purposes only and is not medical advice. GLP-1 medications are prescription drugs with specific indications and risks. Always speak with a qualified healthcare professional before starting, changing, or stopping any medication.

References

1. Müller TD, Finan B, Bloom SR, et al. Glucagon-like peptide 1 (GLP-1). Mol Metab. 2019;30:72-130. doi:10.1016/j.molmet.2019.09.010
2. Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27(4):740-756. doi:10.1016/j.cmet.2018.03.001
3. U.S. Food and Drug Administration. Wegovy (semaglutide) injection: prescribing information [Internet]. Silver Spring (MD): FDA. Available from: Drugs@FDA
4. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038
5. He L, Wang J, Ping F, et al. Association of glucagon-like peptide-1 receptor agonist use with risk of gallbladder and biliary diseases: a systematic review and meta-analysis of randomized clinical trials. JAMA Intern Med. 2022;182(5):513-519. doi:10.1001/jamainternmed.2022.0338
6. Neeland IJ, Linge J, Birkenfeld AL. Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies. Diabetes Obes Metab. 2024;26(Suppl 4):16-27. doi:10.1111/dom.15728
7. Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564. doi:10.1111/dom.14725
8. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563

Brian Opiyo-KRCHN, BscN