HRT Side Effects and Risks by Age: The Real Numbers

Two weeks into hormone therapy your breasts are sore, you are spotting and your jeans feel tight. It is easy to wonder whether this was a mistake. For most women it is the body adjusting, and it usually settles.

The NIH’s MedlinePlus lists breast pain or tenderness, stomach upset, gas, leg cramps and vaginal discharge among estrogen’s side effects to mention if they are severe or do not go away. NICE tells women with a uterus that vaginal bleeding is a common side effect during the first 6 months of systemic HRT, or within 3 months of any change to the dose or product, and that it will be asked about at the 3-month review (NICE NG23, 1.8.4).

This article is general information, not medical advice. Decisions about tests, hormones or contraception belong with a licensed clinician who knows your history.

Estrogen tends to cause breast tenderness, nausea and fluid-type bloating. The progestogen, which women with a uterus need to protect the lining from estrogen, is more often blamed for mood dips and PMS-like symptoms.

That split matters because the fix is different. A clinician may change the route, the product or the type of progestogen rather than stopping altogether. Our explainers on estrogen patch vs gel vs pill and micronized vs synthetic progesterone cover the options.

Relative risks like “41% higher” sound alarming without a starting number. The Women’s Health Initiative (WHI), a randomized trial of 27,347 women aged 50 to 79, gives the absolute numbers. It tested conjugated equine estrogens with or without medroxyprogesterone acetate, which are older products than many women use today (Manson et al., JAMA 2013, PMID: 24084921).

Sources: Manson et al., 2013 for the combined arm and the hazard ratios; the estrogen-alone stroke and hip fracture figures are from the original estrogen-alone report (Anderson et al., JAMA 2004, PMID: 15082697).

Two things stand out. Estrogen alone and combined therapy behave differently for breast cancer. And stroke is the one risk that rose in both arms.

The same pills carried very different absolute risk depending on age at the start. On estrogen plus progestin, excess serious events per 10,000 women a year were 12 at ages 50 to 59, 22 at 60 to 69 and 38 at 70 to 79. On estrogen alone, women aged 50 to 59 had 19 fewer events while women aged 70 to 79 had 51 more (Manson et al., 2013).

Heart disease column: Rossouw et al., JAMA 2007, PMID: 17405972. By time since menopause, the same analysis found 6 fewer heart events per 10,000 women a year within 10 years of the final period, and 17 more at 20 years or later.

This is the “timing hypothesis”: starting under 60 or within 10 years of the final period looks safer than starting later. The Menopause Society’s 2022 statement calls the benefit-risk ratio favorable in that window for women with bothersome symptoms, and less favorable when therapy starts after 60 or more than 10 years out (NAMS 2022, PMID: 35797481). Stroke risk did not follow the same pattern: it was raised overall and did not vary significantly by age or time since menopause (Rossouw et al., 2007).

Starting after 60 and continuing past 60 are different decisions, covered in HRT after 60.

Estrogen taken by mouth passes through the liver first, which raises clotting factors. Estrogen through the skin skips that step.

In UK records covering 80,396 women with a clot, oral HRT was linked to higher clot risk (adjusted odds ratio 1.58) while transdermal HRT was not (0.93) (Vinogradova et al., BMJ 2019, PMID: 30626577). For stroke, low-dose patches were not linked to added risk while oral HRT was (rate ratio 1.28), and higher-dose patches were also linked to more strokes (Renoux et al., BMJ 2010, PMID: 20525678). NICE’s own summary: VTE risk is not increased with transdermal HRT and is greater with oral than transdermal (NICE NG23).

These are observational studies, not trials, so they show associations. No randomized trial has compared routes head to head on clots or stroke.

In November 2025 the FDA asked makers of menopausal hormone therapy to remove cardiovascular disease, breast cancer and probable dementia from the boxed warning. The first revised labels were approved in February 2026. The boxed warning for endometrial cancer remains on systemic estrogen-alone products, and the risks above still appear in the label’s warnings section (FDA, 2025 and 2026).

So the risks did not disappear; they moved out of the box and into context. We cover the full story in what changed on the hormone therapy boxed warning.

Systemic hormone therapy is generally not used, or needs specialist input, for women who have:

• Unexplained vaginal bleeding that has not been investigated.
• Had breast cancer or another estrogen-sensitive cancer.
• Had a blood clot, stroke or heart attack.
• Active liver disease.
• Known clotting disorders, or a current pregnancy.

Many women in these groups can still use low-dose vaginal estrogen or non-hormonal options; that decision is made case by case (NAMS 2022). Vaginal estrogen has its own evidence base, set out in our vaginal estrogen guide.