The "golden window": why the timing of starting hormone therapy matters so much

I've wanted to write about this for a while because I feel it is one of the conversations that happens least in the consulting room, and one of those that changes a woman's decision about hormone therapy the most. It is not only whether to take it or not. It is when.

For years, menopausal hormone therapy (MHT) carried a shadow of fear that comes from a study more than twenty years old, the Women's Health Initiative (WHI), whose results were interpreted, rather hastily, as "hormones are dangerous, full stop". What that study did not explain well is that its participants were aged 50 to 79 and many started treatment long after their last period. And it turns out that matters, a great deal.

What science calls the "window of opportunity"

It is known as the timing hypothesis, or "window of opportunity": the idea that the same estrogens can have different effects depending on whether they are started soon or late after menopause. The position of The Menopause Society (NAMS, 2022) sums it up like this: in women under 60 or within 10 years of menopause and with no contraindications, the benefit-risk balance is favourable for treating vasomotor symptoms and preventing bone loss. For those who start after 10 years or after age 60, it is less favourable because of the greater absolute risk of coronary heart disease, stroke, thrombosis and dementia.

And the heart deserves an honest nuance. The 2015 Cochrane review found that, in women who started MHT less than 10 years after menopause, there was lower mortality and less coronary heart disease than with placebo, although with more risk of thrombosis. But the overall message of that same review is that, taken as a whole, MHT offers little or no benefit for preventing cardiovascular disease. That is why it is not prescribed to protect the heart: it is prescribed for symptoms, and timing influences the balance of risks.

What the evidence says

• When: a 2026 review of the WHI notes that starting MHT before age 60 or within 10 years of menopause may confer cardiovascular benefit, whereas starting late (from age 65) increases the risk of coronary events and stroke.
• According to your risk: the document from the European Menopause and Andropause Society (EMAS, 2022) proposes adapting the type and route of MHT to each woman's cardiovascular risk, and in high-risk women it considers the transdermal route if systemic treatment is needed.
• The route matters: in a large UK study (BMJ, 2019), oral MHT was associated with a higher risk of thrombosis (OR 1.58) and transdermal was not (OR 0.93). That is why the transdermal route (patch, gel, spray) is usually considered when there are other risk factors.
• The brain is the most debated part: the 2026 review of the WHI indicates that starting MHT early does not change cognitive function, whereas starting it late increases the risk of dementia. A large Danish study (BMJ, 2023) found more dementia diagnoses among users of combined MHT, even when started at age 55 or younger, although its authors caution that it is not known whether this is a real effect or reflects other factors. That is why MHT is not used to protect the brain, and the European Society of Endocrinology guideline (2025) considers its role in preventing chronic disease controversial.
• United States: in November 2025 the FDA began removing several boxed warnings from MHT products (those on cardiovascular disease, breast cancer and probable dementia) and kept the one on endometrial cancer for systemic estrogen-only products. It is a US decision; in Spain, product information is regulated by the AEMPS.

What about doses? I want to be very careful here

I know many of you ask me about specific doses, and I understand the wish for a number to hold on to. But precisely because I take this seriously, I prefer to tell you what the officially authorised product information in Spain says, rather than give you a number to repeat at the pharmacy.

For example, for oral estradiol valerate (Progynova), the summary of product characteristics says to start with two 1 mg tablets a day and, after a while, the doctor may reduce this to one tablet. For the estradiol patch (Estradot), there are strengths of 25, 37.5, 50 and 75 micrograms per 24 hours, changed twice a week, and the dose is adjusted according to clinical response. All of them agree on the principle of using the lowest effective dose for the shortest time possible, and that if you still have your uterus a progestogen must be added. But the person who decides your dose, your route of administration and whether you need progesterone is your gynaecologist, with your full medical history in front of her, not a general publication like this one.

When is it worth going to ask?

If you are in perimenopause or have gone less than 10 years without a period, and symptoms (hot flushes, sleep, mood, dryness) are affecting your life, this is exactly the conversation I want to encourage you to have with your gynaecologist. You don't have to wait until it is unbearable. And if more than 10 years have passed since your last period, that is not an automatic "no" either: the conversation about risks and benefits will simply be different, which is why it is even more important to have it with someone who knows your full history.

What I would most like you to take away from this post is this: timing matters. Asking at 48 is not the same as asking at 63. And it is worth asking on time, instead of letting fear inherited from twenty years ago decide for you.

With love,
Alma

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