Hormone therapy, prescribed on current evidence

Hormone therapy is the most effective treatment available for hot flashes and night sweats, and it is also the treatment most distorted by twenty-five years of misreporting. A generation of women stopped taking it, and a generation of physicians stopped offering it, on the basis of headlines that did not accurately describe the study behind them. What follows is what the evidence actually says, where it is solid, where it is contested, and how we decide with you whether hormone therapy is a reasonable choice.

What the Women's Health Initiative actually found

The WHI was a large randomized trial with two separate hormone arms. Women with a uterus received conjugated equine estrogen plus medroxyprogesterone acetate; women who had had a hysterectomy received conjugated equine estrogen alone. Both arms were stopped early, and the resulting coverage collapsed two different findings into one message: that hormone therapy causes breast cancer and heart attacks. That is not what the trial showed.

Three details matter. First, participants were on average in their early sixties at enrollment, more than a decade past menopause for most; the trial tested chronic disease prevention in older women, not symptom relief in women who had just finished their periods. Second, it tested one oral estrogen and one synthetic progestin, not the range of preparations used today. Third, the absolute risks were small: the combined arm showed increases in breast cancer, stroke, and venous thromboembolism alongside reductions in hip fracture and colorectal cancer, and the investigators classified the excess events as rare by conventional criteria, a difference of several events per ten thousand women per year.

The estrogen-alone arm told a different story again, and that part was barely reported. Women taking estrogen without a progestin did not show an increase in breast cancer; in long-term follow-up their incidence was lower than in the placebo group, though they did show more stroke and more clots. Later analyses stratified by age found that women who began hormone therapy in their fifties had a more favorable balance than the trial average, and that observation reframed the field.

The timing hypothesis and the window of initiation

The current framing, reflected in the Menopause Society position statement and in ACOG guidance, is that when you start matters as much as what you start. For women under 60, or within ten years of their final period, who have bothersome vasomotor symptoms and no contraindication, the benefits of systemic hormone therapy generally outweigh the risks. Outside that window the calculus shifts: starting estrogen for the first time in your late sixties carries more cardiovascular and stroke risk and less to gain, because established plaque responds to estrogen differently from healthy vessel wall.

Two groups deserve separate mention. Women with premature or early menopause, spontaneous or surgical, are generally advised to take hormone therapy at least until the average age of natural menopause, because untreated early estrogen deficiency carries substantial bone and cardiovascular risk. Women whose only significant symptoms are vaginal and urinary usually need no systemic therapy at all, since local vaginal estrogen treats that better and with negligible systemic exposure.

Choosing a regimen

Route of estrogen

Oral estrogen passes through the liver before reaching the circulation, which raises the production of clotting factors; transdermal estradiol, delivered by patch, gel, or spray, bypasses that first pass. Observational data consistently show a lower risk of venous thromboembolism with transdermal delivery, and probably a lower stroke risk, though no large randomized trial has compared the two directly, so this is a well-supported inference rather than a proven fact. We tend to prefer transdermal estradiol, and prefer it strongly if you have a higher BMI, migraine with aura, hypertension, high triglycerides, or a history of clotting.

The progestogen requirement

If you have a uterus, estrogen alone causes endometrial hyperplasia and eventually endometrial cancer, so a progestogen is not optional and not a matter of preference. Micronized progesterone is FDA-approved, structurally identical to what your ovary made, taken at bedtime because it is mildly sedating, and is a reasonable first choice; observational data hint at a lower breast cancer signal than older synthetic progestins, which is encouraging but not established by randomized evidence. A levonorgestrel intrauterine device gives excellent endometrial protection and is widely used for this in the United States, though that use is not an FDA-approved indication.

Who should not take it

Genuine contraindications are few but firm: current or past breast cancer, other estrogen-dependent cancer, undiagnosed vaginal bleeding, active or recent venous thromboembolism, a known high-risk thrombophilia, recent myocardial infarction or stroke, active liver disease, and pregnancy. Established coronary artery disease is generally a contraindication to starting systemic therapy. Well-controlled hypertension, diabetes, a family history of breast cancer, fibroids, and migraine without aura are not automatic contraindications, though each changes the conversation and some change the route.

Breast cancer, stated plainly

Combined estrogen and progestogen therapy is associated with a small increase in breast cancer risk that emerges after roughly three to five years of use and rises with duration. The increase is real. It is also small in absolute terms, of a similar order to the risk associated with drinking a couple of glasses of wine a night or with carrying significant excess weight after menopause, neither of which generates the same alarm. Estrogen-alone therapy in women without a uterus did not show this increase in the WHI. A large 2019 collaborative reanalysis of observational data reported excess risk with essentially all systemic regimens, persisting for some years after stopping; its methods have been debated, and it sits alongside rather than replaces the randomized evidence.

So the breast cancer question is one of degree and duration rather than yes or no, and it should be weighed against what you are actually getting. If hormone therapy has given you back your sleep, that is a real gain to set against a small risk, and you are entitled to make that trade knowingly. If you are taking it out of habit and feel no different, the calculation changes.

Almost every serious decision in medicine is a trade. Our job is to make sure you are told the size of both sides of it, not just the frightening half.

Monitoring and how long to continue

We review hormone therapy at least annually, covering symptom control, dose, bleeding, blood pressure, and whether you are up to date with mammography and cervical screening. Unscheduled bleeding after the first few months is investigated rather than watched. Routine blood hormone levels are unnecessary on standard FDA-approved regimens, because the dose is titrated to symptoms rather than to a number on a report.

Stopping at five years, or at 65, is a convention and not a finding. Neither the Menopause Society nor ACOG supports arbitrary discontinuation, and for some women continuing past 65 at an appropriate dose is entirely reasonable, particularly where vasomotor symptoms persist or bone protection matters. Duration should be reviewed periodically on the same basis as the original decision: what you are gaining, what the risks are at your current age, and what you want. Tapering rather than stopping abruptly reduces the chance of rebound symptoms, though it does not always prevent them.

Compounded bioidentical hormones and pellets

There is an important distinction buried in the word bioidentical. Estradiol and micronized progesterone are bioidentical, FDA-approved versions of both exist, and we use them routinely. What is marketed as bioidentical hormone therapy is usually something else: custom-compounded preparations made outside the FDA approval process, often dosed on the basis of saliva testing, which is not a validated way to guide dosing. Compounded products are not tested for potency or batch consistency, carry no labeling requirement to disclose risks, and have never been shown to be safer or more effective than approved products; a 2020 National Academies report reached the same conclusion and recommended restricting their use.

Hormone pellets are offered by our practice after an individualized consultation. Pellets release hormone over several months and are harder to adjust or stop than a daily preparation. We discuss alternatives, the exact product’s approval status, monitoring, and risks before treatment. Compounded hormone products are not FDA-approved and have not been shown to be safer or more effective than approved products.