The Menu: Types, Routes, and What They're For

Women often go into an appointment prepared to discuss whether to take HRT, and come out having been handed a specific product without any conversation about why that one. Understanding the components makes that conversation possible.

There are essentially three decisions: which estrogen and by what route, whether you need a progestogen and which, and what pattern you take it in.

The estrogen

Estradiol is chemically identical to the estrogen your ovaries produce. It's the standard choice in most current UK prescribing and increasingly elsewhere. When people say "body-identical", this is what they mean — a regulated pharmaceutical product with a molecular structure matching your own hormone.

Conjugated equine estrogens are derived from pregnant mares' urine and contain a mixture of estrogens. This is what the Women's Health Initiative used. Still prescribed, particularly in the US.

The distinction matters because most of the risk data everyone quotes comes from studies of the second, and it isn't automatically transferable to the first.

The route, which matters more than expected

Transdermal — patch, gel or spray. Estradiol is absorbed through the skin and enters the bloodstream directly, bypassing the liver's first-pass metabolism. That matters because first-pass metabolism is what drives the changes in clotting factors associated with oral estrogen. Transdermal estrogen has not been shown to increase venous thromboembolism risk, which is why guidance recommends it where clot risk is elevated — including a BMI over 30.

Oral — a daily tablet. Convenient, effective, and carries a small increased clot risk that transdermal doesn't.

Vaginal — cream, pessary, tablet or ring. This is a different category entirely: low-dose, acting mostly locally, for genitourinary symptoms. It doesn't treat hot flushes, doesn't usually require a progestogen alongside it, and can be used at the same time as systemic HRT if you need both.

The progestogen, and why

If you have a uterus and take systemic estrogen, you need a progestogen. Not optional. Unopposed estrogen thickens the endometrium and raises the risk of endometrial cancer, and this is the one boxed warning the FDA retained in its 2025 revision.

If you've had a hysterectomy, you generally don't need one.

Micronised progesterone is structurally identical to the progesterone your body produces. Usually taken as a capsule at night, since it has a mild sedative effect that many women find useful. Current evidence suggests a more favourable breast and cardiovascular risk profile than older synthetic progestogens, though the comparative data is not definitive.

Synthetic progestogens — norethisterone, medroxyprogesterone acetate, dydrogesterone, levonorgestrel and others. Effective for endometrial protection. Side effect profiles differ between them, which is worth knowing: if one makes you feel awful, switching to another is a real option rather than a reason to abandon HRT.

The hormonal intrauterine system provides endometrial protection, works as contraception, and reduces heavy bleeding — three problems, one device. It's a common choice in perimenopause for exactly that reason.

The pattern

Sequential (cyclical) — estrogen every day, progestogen for around 10–14 days each month. Produces a monthly bleed. This is the usual choice for women still having periods, because giving continuous progestogen too early tends to cause erratic breakthrough bleeding.

Continuous combined — both every day, no bleed. Usually appropriate once you're past 12 months without a period, or after a period on sequential.

Some irregular bleeding in the first three to six months after starting or changing is expected. Bleeding that starts after things have settled, or persists beyond that window, should be reported.

Other things you may hear about

Tibolone is a synthetic compound with estrogenic, progestogenic and weak androgenic activity. Taken as a single tablet, no separate progestogen needed. An option for some postmenopausal women.

Testosterone is not standard HRT and is discussed separately. International consensus supports it only for hypoactive sexual desire disorder in postmenopausal women, usually after estrogen is already optimised.

Compounded "bioidentical" hormones are a different thing again — custom-mixed preparations, often marketed with saliva testing, outside standard regulation. Professional bodies including ACOG and The Menopause Society advise against them, and a 2020 US National Academies review found the evidence did not support their use. This is genuinely distinct from regulated body-identical estradiol and micronised progesterone, and the similarity of the words causes real confusion.

Dose and adjustment

Standard practice is to start at a low-to-moderate dose and adjust based on symptom response. Full effect takes around three months, so judging after two weeks is judging too early.

If it isn't working, the options before abandoning it are: increase the dose, change the route, change the progestogen, or change the pattern. Many women who conclude "HRT didn't work for me" were on one formulation, at one dose, for a short time.

Reasonable questions for the appointment: why this estrogen, why this route given my risk factors, which progestogen and why, and when should we review.

Sources

- The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022;29(7):767–794. - National Institute for Health and Care Excellence. Menopause: identification and management (NG23). Updated 2024. - Canonico M, Oger E, Plu-Bureau G, et al. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens (ESTHER study). Circulation. 2007;115(7):840–845. - National Academies of Sciences, Engineering, and Medicine. The Clinical Utility of Compounded Bioidentical Hormone Therapy: A Review of Safety, Effectiveness, and Use. 2020. - British Menopause Society. Tools for clinicians: HRT preparations and equivalent alternatives.