Hormones and aging
Hormones are chemical messengers made by glands such as the ovaries, testes, thyroid, adrenals, and pituitary. Several fall with age, and a large industry sells replacing them. The evidence splits sharply. Replacing a hormone that has failed, as in menopause or true hypogonadism (low testosterone from a problem in the testes or pituitary), can relieve real symptoms and protect bone. Pushing normal levels higher, or treating a number without symptoms, has not been shown to help and sometimes harms.
The optimal approach is to test the right hormones at the right time, treat real deficiencies well, and leave normal levels alone. Drugs aimed at aging itself are in Longevity drugs, and lab details in Blood tests and biomarkers.
Menopause and perimenopause
Menopause is the point 12 months after your final menstrual period. In the US the average age is 52, and most women begin the menopausal transition, or perimenopause, between 45 and 55. Perimenopause can last several years, with irregular periods and fluctuating hormones before estrogen and progesterone settle at low levels.
Symptoms vary from none to disabling. The most common are hot flashes and night sweats (together called vasomotor symptoms), poor sleep, mood changes, joint aches, and brain fog. Vaginal dryness, pain with sex, and urinary urgency or infections, grouped as the genitourinary syndrome of menopause, tend to start later and worsen over time rather than fade.
- 52 average age of menopause in the US (NIA)
- 7.4 years median duration of hot flashes and night sweats (SWAN, 2015)
- 11.8+ years median duration when frequent symptoms start early in perimenopause (SWAN, 2015)
Hot flashes last longer than many people are told. In the Study of Women's Health Across the Nation (SWAN), which followed more than 3,000 US women through the transition, frequent vasomotor symptoms lasted a median of 7.4 years, and more than 11.8 years for women whose symptoms began early in perimenopause. Black women reported the longest durations.
Menopause also accelerates bone loss and shifts cholesterol and body fat in unfavorable directions, which is why it is worth discussing with a clinician even if symptoms are mild. See Muscle, bone, and mobility for bone density screening and Heart and blood vessels for cardiovascular risk.
Planning ahead
The optimal approach is proactive. By your early to mid-40s, before the transition usually begins, raise it at your yearly visit: what to expect, which treatments fit your history, and where your bone density, blood pressure, and ApoB stand. Track cycles, sleep, and symptoms. Perimenopausal symptoms can be treated without waiting for periods to stop, and symptoms that start early tend to last longest.
| Situation | Optimal approach | Evidence |
|---|---|---|
| Bothersome hot flashes, night sweats, or the sleep loss they cause | Hormone therapy if no contraindications, often skin estradiol plus micronized progesterone if you have a uterus | Strong |
| Vaginal dryness, painful sex, or recurrent urinary infections | Low-dose vaginal estrogen, which most women can use | Strong |
| Under 60 or within 10 years of menopause, with raised risk of bone loss or fracture | Hormone therapy is a reasonable way to prevent bone loss, alongside strength training; see Muscle, bone, and mobility | Strong for fractures |
| No symptoms and no bone concern | Hormone therapy only to prevent heart disease or dementia is not supported | Weak for that purpose |
For women under 60 or within 10 years of menopause without contraindications, The Menopause Society's 2022 statement finds the balance favorable for both treating symptoms and preventing bone loss. In the WHI, estrogen plus progestin cut fractures from 11.1% to 8.6% over about five and a half years, although in those older women (average age 63) the fracture benefit did not outweigh the other risks in the trial's overall index. Guideline minimum: the USPSTF recommends against hormone therapy for preventing chronic conditions (grade D, 2022), a recommendation that does not apply to treating symptoms.
Menopausal hormone therapy
Menopausal hormone therapy (MHT, sometimes called HRT) replaces estrogen, with a progestogen added for anyone who still has a uterus. It is the most effective treatment for hot flashes and night sweats Strong and prevents bone loss and fractures Strong, according to The Menopause Society's 2022 position statement, which remains its current hormone therapy guidance as of October 2026.
What the WHI trials found
The Women's Health Initiative (WHI) was a set of large randomized trials that tested hormone therapy in about 27,000 postmenopausal women with an average age of 63. In 2002 the estrogen-plus-progestin trial was stopped early. Compared with placebo, it raised breast cancer, heart disease, stroke, and blood clots in the lungs and lowered hip fractures and colorectal cancer. In absolute terms, for every 10,000 women taking it for a year there were 7 more heart disease events, 8 more strokes, 8 more pulmonary emboli, and 8 more invasive breast cancers, and 6 fewer colorectal cancers and 5 fewer hip fractures. Prescriptions collapsed worldwide.
Later analyses changed the picture. Most risks and benefits faded after women stopped treatment. Estrogen alone, given to women who had had a hysterectomy, did not raise heart disease and was linked to fewer breast cancers over long-term follow-up, while estrogen plus a synthetic progestin raised breast cancer modestly. Across 18 years, neither regimen changed death from any cause, heart disease, or cancer, and results tended to be more favorable for women in their 50s than in their 70s. For relative versus absolute risk, see Reading the evidence.
The timing hypothesis
The leading explanation for the difference by age is the timing hypothesis: estrogen may help healthy blood vessels but not ones that already have advanced plaque. In the ELITE trial, oral estradiol slowed thickening of the carotid artery wall in women who started within six years of menopause but not in women who started ten or more years after Moderate. That is a surrogate measure, not heart attacks, so the timing hypothesis explains the data well without proving that hormone therapy prevents heart disease. No major society recommends it for that purpose.
The 2025 FDA label change
On November 10, 2025, the FDA announced it would remove the boxed warnings about cardiovascular disease, breast cancer, and probable dementia from menopausal hormone therapy labels. The boxed warning about endometrial cancer stays on systemic estrogen-only products, because estrogen without a progestogen thickens the uterine lining. The updated labels say to consider starting systemic therapy within 10 years of menopause or before 60. By February 2026, the agency had approved new labels for six products, including a vaginal estrogen.
The decision drew criticism from both sides: menopause specialists had long said the warnings overstated risk for younger women and vaginal estrogen, while Public Citizen argued some changes went beyond the evidence. The risks in the WHI tables did not disappear; what changed is how prominently they are presented.
Routes and regimens
| Choice | Options | What the evidence says |
|---|---|---|
| Estrogen route | Pill, skin patch, gel, or spray | In UK records, oral estrogen was linked to 58% higher odds of blood clots, while transdermal estrogen showed no increase |
| Estrogen type | Estradiol or conjugated equine estrogens | Oral estradiol carried somewhat lower clot risk than conjugated estrogens in the same study |
| Progestogen (if you have a uterus) | Micronized progesterone, synthetic progestins, or a hormonal IUD | Required to protect the uterine lining; the type may affect breast and clot risk, with micronized progesterone often preferred |
| Vaginal estrogen | Low-dose creams, tablets, rings, or inserts | Treats dryness, painful sex, and urinary symptoms with minimal absorption |
For people with a uterus, estrogen alone raises the risk of endometrial cancer, which is why a progestogen is added. Bleeding after menopause, on or off hormones, always needs evaluation.
Vaginal estrogen
Low-dose vaginal estrogen is one of the safest and most underused treatments in medicine Strong. It treats the genitourinary syndrome of menopause directly, reduces recurrent urinary tract infections, and is absorbed in tiny amounts. In the Nurses' Health Study, women who used vaginal estrogen over 18 years had no higher risk of heart disease, cancer, or hip fracture than nonusers. The Menopause Society's 2020 statement supports it for most women, including many who cannot use systemic hormones; people with a history of breast cancer should decide with their oncologist. Vaginal DHEA (prasterone, approved in 2016) is another option.
Who should not use systemic hormone therapy
Women who start more than 10 years after menopause or after 60 face higher absolute risks of heart disease, stroke, clots, and dementia, according to the 2022 position statement. Stopping at a fixed age is not required: women who started earlier can often continue if symptoms persist, reassessing each year with their clinician.
Compounded "bioidentical" hormones
FDA-approved estradiol and micronized progesterone are already chemically identical to human hormones. Custom-compounded "bioidentical" creams and pellets are different: the FDA does not review them, and a National Academies committee found insufficient evidence that they are safer or more effective than approved products. Pellets deliver unpredictable, often high, doses. Prefer approved products unless you need a dose or form that does not exist.
Non-hormonal treatment for hot flashes
For people with a contraindication or a preference to avoid hormones, The Menopause Society's 2023 nonhormone statement recommends cognitive behavioral therapy, clinical hypnosis, certain antidepressants, gabapentin, and fezolinetant Strong, with oxybutynin, weight loss, and a nerve block called stellate ganglion block as further options. It recommends against most supplements and herbal remedies, soy products, paced breathing, and acupuncture for hot flashes.
| Treatment | How it works | Notes |
|---|---|---|
| Fezolinetant (Veozah) | Blocks the brain's NK3 receptor, part of the temperature-control circuit | Approved May 2023; boxed warning for liver injury, with liver tests before and during the first nine months |
| Elinzanetant (Lynkuet) | Blocks NK1 and NK3 receptors | Approved October 2025; taken at bedtime; can cause sleepiness; liver tests before starting and at three months |
| Low-dose paroxetine (Brisdelle) | An SSRI antidepressant at 7.5 mg | Approved in 2013 specifically for hot flashes; interacts with tamoxifen |
| Other SSRIs and SNRIs (escitalopram, venlafaxine) | Antidepressants | Used off-label; also help mood symptoms |
| Gabapentin | Nerve-pain drug | Useful for night sweats; causes drowsiness |
| Cognitive behavioral therapy and hypnosis | Psychological treatments | Reduce how much hot flashes bother you, with no drug side effects |
Testosterone
Diagnosis in men
Testosterone falls slowly with age, and symptoms commonly blamed on it (fatigue, low libido, weight gain, low mood) have many other causes. The Endocrine Society's 2018 guideline recommends diagnosing hypogonadism only when a man has symptoms or signs of testosterone deficiency and consistently low levels, below the lower limit of normal (about 264 ng/dL in the guideline's harmonized reference range). The American Urological Association uses 300 ng/dL as its cutoff. Levels are highest in the morning and fall with illness, poor sleep, heavy training, obesity, and opioids, so a single afternoon test is not a diagnosis.
If you have symptoms, the optimal workup is thorough and follows the guideline closely:
- Total testosterone, twice. Fasting, before about 10 a.m., on two mornings, from a reliable lab.
- Free testosterone when the total is near the cutoff or SHBG (sex hormone-binding globulin, the protein that carries testosterone) is likely altered, as with obesity, diabetes, or aging; measured by equilibrium dialysis or calculated with an accurate formula.
- LH and FSH, pituitary hormones that show whether the problem is in the testes or the brain, with prolactin and iron studies if they point to the brain.
- A baseline blood count and PSA, because testosterone raises hematocrit, and the guideline advises against starting it with a PSA above 4 ng/mL (3 at higher prostate cancer risk) without a urology evaluation.
- The reversible causes: sleep apnea, obesity, heavy drinking, opioids, and hard training on too little food. Weight loss raises levels. See Sleep and Metabolic health.
If your levels are normal, testosterone is not the treatment for your symptoms. Even TRAVERSE, the large safety trial below, enrolled only men with symptoms and two fasting levels below 300 ng/dL. Testing men without symptoms is not useful, and a number that is "low for your age" or below a clinic's "optimal" range is not a diagnosis.
Benefits and safety in men
In men with confirmed hypogonadism, testosterone improves libido and sexual function, and modestly improves mood, bone density, and anemia Moderate. It is not a proven treatment for energy, cognition, or longevity.
The biggest safety question was the heart. TRAVERSE, a randomized trial of 5,246 men aged 45 to 80 with low testosterone and existing or high cardiovascular risk, found that testosterone gel did not increase heart attacks, strokes, or cardiovascular death compared with placebo (7.0% vs 7.3%) Strong. It did show more atrial fibrillation, acute kidney injury, and pulmonary embolism. A substudy found more fractures, not fewer, with testosterone (3.5% vs 2.5%). In February 2025 the FDA removed the language about increased cardiovascular outcomes from the boxed warning of all testosterone products, added class-wide warnings about raised blood pressure, and kept the statement that testosterone is not approved for age-related low testosterone alone.
Alternatives that preserve fertility
For men with low testosterone from a pituitary signaling problem who want to keep fertility, doctors sometimes use off-label drugs that raise the body's own production, such as clomiphene (a fertility drug that blocks estrogen's feedback on the brain) or hCG injections. The AUA guideline advises that testosterone should not be prescribed to men who are trying to conceive. Enclomiphene, a component of clomiphene sold widely online, is not FDA-approved and is available only through compounding pharmacies.
Testosterone clinics
Direct-to-consumer "low T" clinics have made testosterone easy to start and hard to evaluate. Red flags include diagnosis from a single test or a symptom questionnaire, a target level far above the normal range, routine add-on drugs to suppress estrogen, little discussion of fertility, and no plan to check hematocrit. If you use one, share every lab result with your primary care doctor.
Testosterone for women
Testosterone is also a normal hormone in women. The 2019 Global Consensus Position Statement, endorsed by endocrine and menopause societies worldwide, concluded that the only evidence-based use is for postmenopausal women with hypoactive sexual desire disorder (persistent low desire that causes distress), after other causes are addressed Moderate. The benefit is modest, and the statement does not support testosterone for energy, mood, cognition, bone, or muscle. No testosterone product is FDA-approved for women, so US doctors prescribe a small fraction of a male product off-label, aiming for the normal female range. Compounded pellets and creams are discouraged because doses are unpredictable.
Thyroid
The thyroid gland sets the pace of metabolism. True hypothyroidism (an underactive thyroid) causes fatigue, weight gain, cold intolerance, and constipation, and is easily treated with levothyroxine Strong. The harder question is subclinical hypothyroidism: a mildly high thyroid-stimulating hormone (TSH, the pituitary's signal to the thyroid) with a normal thyroid hormone level.
Testing. TSH is the single best screening test for thyroid function, and it is cheap. The optimal plan is a TSH at about 35 and at least every five years after, as the American Thyroid Association advised in 2000, or yearly with your blood work; test sooner with symptoms, a family history or another autoimmune disease, plans for pregnancy, or an unexplained rise in LDL, which an underactive thyroid can cause Weak. A normal TSH stayed normal in 98% of 422,242 people over five years, while more than half of abnormal results were normal on repeat, so repeat an abnormal result before acting. Guideline minimum: the USPSTF finds insufficient evidence to screen adults without symptoms.
Treatment. In the TRUST trial of 737 adults aged 65 and older with subclinical hypothyroidism, levothyroxine lowered TSH but produced no improvement in symptoms or tiredness after a year Negative. A 2019 BMJ guideline panel made a strong recommendation against thyroid hormone for most adults with subclinical hypothyroidism, with exceptions such as TSH above 20, pregnancy or plans for pregnancy, and severe symptoms. TSH also drifts upward with normal aging.
Testing the blood is not the same as scanning the gland. Skip thyroid ultrasound unless a doctor feels a lump or you have symptoms: the USPSTF recommends against screening for thyroid cancer (grade D), and South Korea's screening boom produced a surge in diagnoses with no fall in deaths.
DHEA and growth hormone
DHEA
DHEA is an adrenal hormone that falls steadily with age and is sold as an over-the-counter supplement. In a two-year randomized trial of older men and women, DHEA raised blood levels but had no effect on body composition, physical performance, insulin sensitivity, or quality of life Negative. Supplement quality is variable, and DHEA can convert to testosterone and estrogen. The vaginal form, prasterone, is an approved, effective treatment for painful sex after menopause; oral DHEA for aging is not.
Growth hormone and IGF-1
Growth hormone (GH) and the hormone it triggers, IGF-1, fall with age. A systematic review of trials in healthy older adults found it added about 2 kg of lean mass and removed about 2 kg of fat without improving strength or fitness, while causing swelling, joint pain, carpal tunnel syndrome, breast enlargement, and a trend toward diabetes Negative. Distributing GH for anti-aging or bodybuilding is illegal in the US; it is approved only for specific deficiency and wasting conditions.
Growth hormone "secretagogues" (drugs that make the pituitary release more GH), such as ipamorelin, CJC-1295, and ibutamoren (MK-677), are a gray-market workaround. The FDA lists several as substances that may present significant safety risks in compounding, citing immune reactions, impurities, and, for ibutamoren, a possible heart failure signal. See peptides and the gray market.
Cortisol and adrenal fatigue
Cortisol, the adrenal stress hormone, follows a daily rhythm and rises with stress. "Adrenal fatigue," the idea that chronic stress exhausts the adrenal glands and causes tiredness, is not a recognized medical diagnosis. A systematic review of 58 studies concluded that adrenal fatigue does not exist as a measurable condition Negative. Saliva cortisol panels sold to diagnose it are not reliable for that purpose.
Real adrenal disorders do exist: adrenal insufficiency (Addison's disease), which causes weight loss, low blood pressure, and salt craving, and excess cortisol (Cushing's syndrome), which causes weight gain in the trunk and high blood pressure. Both are diagnosed with specific tests by an endocrinologist. Taking hydrocortisone or "adrenal support" glandular supplements without a diagnosis can suppress your own adrenal glands. Persistent fatigue deserves an evaluation for sleep apnea, depression, anemia, thyroid disease, and medication effects; see Mind and connection and Sleep.
Sexual health
Erectile dysfunction as a warning sign
Erectile dysfunction (ED) often shares a cause with heart disease: damaged blood vessels. In a large prostate cancer prevention trial, ED was linked to a 45% higher risk of later cardiovascular events, comparable to smoking or a family history of heart disease Moderate. New ED, especially in men under 60, is a reason to check blood pressure, cholesterol, ApoB, and glucose. See Heart and blood vessels.
PDE5 inhibitors (sildenafil, tadalafil, and related drugs) are effective and widely available. They must never be combined with nitrates such as nitroglycerin, which can cause a dangerous drop in blood pressure; the label lists this as a contraindication. Buy them from a licensed pharmacy: sexual-enhancement supplements are the category most often spiked with hidden sildenafil.
Sexual health in women
Low desire, arousal problems, and pain are common and treatable. Vaginal estrogen or prasterone treats pain from menopause-related dryness; pelvic floor physical therapy helps many forms of pain; and testosterone has a narrow role for postmenopausal low desire, as described above. Relationship and mental health factors matter as much as hormones, and sex therapists can help; see Mind and connection.
Prostate enlargement
Benign prostatic hyperplasia (BPH), noncancerous growth of the prostate, becomes common with age and causes weak stream, frequent urination, and waking at night to urinate. It does not cause prostate cancer, but the symptoms overlap, so new urinary symptoms deserve an exam. Treatments range from limiting evening fluids to medicines and minimally invasive procedures. Prostate cancer screening decisions are in Cancer.