Hormone Replacement Therapy (HRT)

What is hormone replacement therapy?

Hormone replacement therapy (HRT) means supplementing hormones that decline with age, restoring them to levels where the body functions better. Most people associate HRT with estrogen and progesterone during menopause, but it also includes testosterone replacement for men and women, DHEA supplementation, and thyroid hormone optimization. In longevity medicine, hormone optimization sits alongside exercise, nutrition, and sleep as a core strategy for healthy aging ^[1].

Hormone replacement therapy for perimenopause and menopause

Menopausal hormone therapy (MHT) typically involves estrogen alone for women who've had a hysterectomy, or combined estrogen plus progestogen for women with an intact uterus. Delivery options include oral tablets, transdermal patches, topical gels, and vaginal preparations. Transdermal estrogen avoids the liver's first-pass metabolism, which means it doesn't raise clotting risk the way oral estrogen can. This distinction matters when choosing between formulations ^[2].

Bioidentical hormone replacement therapy (BHRT) uses hormones chemically identical to those the body produces: 17-beta estradiol, micronized progesterone, and testosterone. FDA-approved bioidentical options are well-regulated and backed by clinical data. Compounded bioidentical preparations, on the other hand, lack standardized dosing and quality oversight. The North American Menopause Society doesn't recommend compounded products when FDA-approved alternatives are available ^[3].

What the evidence says about longevity

The timing of HRT initiation is the single most important factor determining its benefits. Women who start estrogen during perimenopause or within 10 years of menopause onset see the greatest cardiovascular and neurological gains. Data presented at the 2025 Menopause Society meeting showed that women starting estrogen in perimenopause had roughly 60% lower odds of heart attack, stroke, and breast cancer compared to never-users ^[4].

The Leisure World Cohort Study followed over 8,800 women for 22 years and found that long-term estrogen users had significantly lower all-cause mortality, with the strongest benefit in women who used estrogen for 15 or more years ^[5]. A 2024 JAMA Network Open study of 117,763 postmenopausal women added a new dimension: women who had used hormone therapy were biologically younger according to aging biomarkers than non-users, and this younger biological age partially explained their lower mortality risk ^[6].

For women over 65, a large 2024 analysis of 10 million Medicare beneficiaries found that continued estrogen monotherapy was associated with 19% lower mortality, 16% lower breast cancer risk, and 11% lower heart attack risk. Low-dose transdermal estradiol showed the best safety profile ^[7].

Testosterone replacement therapy and cardiovascular safety

The landmark TRAVERSE trial enrolled 5,246 men aged 45 to 80 with hypogonadism and high cardiovascular risk. The result: testosterone replacement therapy did not increase heart attacks or strokes compared to placebo (7.0% vs 7.3%). Based on these findings, the FDA removed the cardiovascular black box warning from all testosterone products in February 2025. The trial did note higher rates of atrial fibrillation and pulmonary embolism, so monitoring remains important ^[8].

Signs you may need hormone replacement therapy

Common signs of hormone deficiency that may warrant evaluation include persistent hot flashes, night sweats, sleep disruption, vaginal dryness, mood changes, brain fog, joint pain, and loss of libido. In men, symptoms include fatigue, reduced muscle mass, increased body fat, low motivation, and erectile dysfunction. Blood work measuring estradiol, progesterone, total and free testosterone, SHBG, and thyroid hormones provides the objective picture needed before starting therapy.

Risks and who should be cautious

HRT isn't risk-free. Oral estrogen raises venous thromboembolism risk, though transdermal delivery largely avoids this. Combined estrogen-progestogen therapy started more than 10 years after menopause may increase breast cancer risk, while estrogen-only therapy and regimens using micronized progesterone have lower risk profiles. The 2025 Lancet Healthy Longevity systematic review concluded that current evidence doesn't support prescribing MHT solely for dementia prevention, despite promising observational data ^[9].

Women with a history of breast cancer, active liver disease, unexplained vaginal bleeding, or known clotting disorders need careful individual assessment. For most symptomatic women under 60, the benefits clearly outweigh the risks when therapy is properly supervised.

HRT and weight: what the research shows

Many women worry that HRT causes weight gain, but the evidence points in the opposite direction. Weight gain during perimenopause results from metabolic changes driven by declining hormones, not from HRT itself. Studies show that estrogen therapy actually reduces overall fat mass, particularly abdominal fat, and improves insulin sensitivity. Women on hormone therapy gained about 1 kg less over three years compared to placebo groups ^[10].