Why Absolute Numbers Matter

Risk in medicine is almost always reported in relative terms — "increases risk by 26%" sounds alarming. The absolute number behind that figure — how many actual people are affected — tells a very different story. Throughout this post, I'll use absolute numbers: excess cases per 10,000 women per year, or per 10,000 women over a defined period. That's the only way to make a genuinely informed decision.

Breast Cancer: The Most Important Number to Understand

Breast cancer risk is the concern most women raise first when considering MHT, and it deserves a careful, honest answer — not reassurance that papers over the evidence, and not alarm that ignores context. The key distinction is between combined estrogen-progestogen therapy and estrogen alone.

📊 The Evidence — Breast Cancer Risk in Absolute Terms

For combined estrogen-progestogen therapy, the WHI trial found approximately 9 excess breast cancer cases per 10,000 women per year. Over 5.6 years of use, that translates to roughly 51 excess cases per 10,000 women.[1][2] A large individual-participant meta-analysis quantified the 20-year absolute risk increase more precisely: for women starting combined therapy at age 50, the excess risk is approximately 2 in 100 women (1 in 50) with daily progestogen, and 1.4 in 100 (1 in 70) with intermittent progestogen.[3] Risk increases progressively with duration — the relative risk rises from 1.60 after 1–4 years to 2.51 after 15 or more years of combined therapy.[3]

For estrogen-alone therapy, the picture is strikingly different. The WHI estrogen-only arm — women who had had hysterectomies — actually showed a reduction in breast cancer incidence (HR 0.78) and breast cancer mortality (HR 0.60), a protective effect that persisted for over a decade after stopping.[4] The 20-year absolute risk increase for estrogen alone is only about 0.5 per 100 women (1 in 200) — a fraction of the combined therapy risk.[3]

Importantly, observational data consistently suggest that micronized progesterone carries a lower breast cancer risk signal than synthetic progestins like medroxyprogesterone acetate.[5] The WHI used synthetic progestin; the breast cancer signal in combined therapy may be substantially lower with modern preferred formulations, though large RCT confirmation is not yet available.

⚠ My Recommendation — Mammography on MHT Because of the increased breast cancer risk associated with combined hormone therapy, I recommend annual mammograms for all women on MHT who are 50 or older — even those who would otherwise qualify as low risk. This is a deliberate divergence from my usual approach: for low-risk women not on MHT who are doing regular self-exams, the overall mortality benefit of routine mammography is limited enough that in some cases I don't require it, and I support patients who make an informed choice to skip routine screening. MHT changes that calculation. The modest but real increase in breast cancer risk with combined therapy warrants annual surveillance, and catching any cancer earlier is the most meaningful way to mitigate that risk in practice.

The broader evidence on cancer screening — what it does and doesn't reduce, and how to think about it for low-risk individuals — is something I'll cover in a dedicated series on cancer screening.

Other Risks — With Absolute Numbers

Beyond breast cancer, MHT carries other risks worth understanding in concrete terms. The table below uses WHI data for combined therapy over 5.6 years and estrogen-only therapy over 7.2 years, per 10,000 women.

Risk Combined therapy Estrogen alone
Breast cancer +51 cases per 10,000 over 5.6 yrs Reduced (HR 0.78)
VTE (blood clots) +120 cases per 10,000 over 5.6 yrs +77 cases per 10,000 over 7.2 yrs
Stroke +52 cases per 10,000 over 5.6 yrs Modest increase
Gallbladder disease +260 cases per 10,000 over 5.6 yrs Increased
Coronary heart disease Modest increase (older starters) No significant increase
Colorectal cancer Reduced No significant change
Hip fracture Reduced 34% Reduced
All-cause mortality (ages 50–59) Reduced 31% Net benefit
⚠ VTE Risk — A Note on Route Venous thromboembolism risk is elevated with both forms of MHT, but the route of estrogen delivery matters significantly. Oral estrogen undergoes first-pass metabolism in the liver, activating clotting factors in a way that transdermal estrogen does not. Observational data consistently show lower VTE risk with transdermal estradiol compared to oral formulations. For women with personal or family history of VTE, or other thrombophilic risk factors, transdermal estrogen is strongly preferred.[5][6]

The Progesterone Question: Women Without a Uterus

This is one of the most clinically important and most commonly overlooked points in MHT prescribing: women who have had a hysterectomy should receive estrogen only. Adding progestogen when there is no uterus to protect provides no benefit and adds meaningful risk.

📊 The Evidence — No Progesterone After Hysterectomy

The sole purpose of adding progestogen to estrogen therapy is to protect the endometrium (uterine lining) from hyperplasia and cancer that unopposed estrogen would otherwise cause. Without a uterus, there is no endometrium to protect.[7]

Multiple lines of evidence suggest that combined estrogen-progestogen regimens carry greater breast cancer risk than estrogen alone — and provide no additional vasomotor symptom relief beyond what estrogen alone achieves.[7] The WHI demonstrated this directly: breast cancer risk increased in the combined arm but was actually reduced in the estrogen-only arm. Observational data further suggest that adding progestogen may attenuate some of the cardiovascular benefit that estrogen alone provides.[7]

The one exception is women with a history of endometriosis after hysterectomy, who may require progestogen to prevent stimulation of residual endometrial tissue by unopposed estrogen.[8]

My Synthesis When I see a woman who has had a hysterectomy on combined estrogen-progestogen therapy, the first question I ask is why. Sometimes there's a documented reason — prior endometriosis, a provider's preference. More often, it's because no one revisited the prescription after the surgery. Estrogen alone in a woman without a uterus has a substantially better risk profile than combined therapy — particularly for breast cancer — and she deserves that more favorable profile. Switching her to estrogen-only is one of the most straightforward, evidence-supported improvements I can make to an existing MHT regimen.

Extended Use: The Age-Dependent Calculation

How long MHT can or should be continued is one of the most common questions I hear from patients who are doing well on treatment and don't want to stop. The honest answer is that there is no mandatory discontinuation age — but the risk-benefit balance does shift with time, and that shift is real.

📊 The Evidence — Age and Duration

The WHI global index — a composite measure of benefits and harms — showed dramatically different results by age. Women aged 50–59 on estrogen alone had 19 fewer adverse events per 10,000 person-years than placebo — a net benefit. Women aged 70–79 had 51 more adverse events per 10,000 person-years — a net harm.[9] For breast cancer specifically, 10 years of combined therapy approximately doubles the excess risk compared to 5 years of use.[3]

For women who want to continue beyond the period where symptom relief is the primary driver, the decision becomes more individualized. All major societies agree there is no mandatory stopping age, and some women — those with persistent symptoms, high quality-of-life impact, or surgical menopause — may benefit from extended therapy beyond the conventional 5-year window.[6][8] The key is that this decision is made with full information about how the risk profile changes, not by default or inertia.

Who Shouldn't Take MHT

Absolute contraindications

  • Personal history of estrogen receptor-positive breast cancer
  • Unexplained vaginal bleeding
  • Active or recent arterial thromboembolic disease (heart attack, stroke)
  • Active VTE or high-risk thrombophilia
  • Active liver disease with abnormal liver function
  • Known or suspected pregnancy
  • Untreated endometrial hyperplasia

Relative contraindications — individualize

  • History of VTE (transdermal estrogen substantially reduces but may not eliminate risk)
  • Controlled hypertension (transdermal preferred)
  • Well-controlled migraine with aura (oral estrogen may worsen; transdermal preferred)
  • Receptor-negative breast cancer history (requires oncology consultation)
  • BRCA carriers without personal breast cancer history (HRT until age 51 is generally supported)
  • Gallbladder disease (oral estrogen increases risk; transdermal less so)
My Synthesis The risk conversation about MHT is most useful when it's specific. A healthy 52-year-old with no personal or strong family history of breast cancer, no VTE history, and severe vasomotor symptoms has a very different risk profile than a 67-year-old 15 years past menopause considering MHT for bone health. I use absolute numbers — not percentages, not relative risks — and I put them in context: an excess risk of 1 in 50 for breast cancer over 5 years of combined therapy is real and worth knowing; it is also smaller than the risk from obesity, alcohol use, or having a first-degree relative with breast cancer. The goal is an informed shared decision, not a list of frightening statistics delivered without context.

For women who want to continue MHT beyond the conventional window because they feel significantly better on it and have discussed the evolving risk profile, I support that decision. Autonomy matters. What I'm doing is making sure the decision is genuinely informed — with the absolute numbers, the distinction between formulations, and a clear picture of what we know and what we don't.