The Rise and Fall of Modern HRT

To appreciate the significance of this reversal, we need to look back at the complex history of hormone therapy. Modern HRT emerged in the mid-20th century with the introduction of estrogen-containing medications, which quickly proved highly effective for treating hot flashes, night sweats, sleep disturbances, and urogenital symptoms. By the 1960s, estrogen was widely viewed as a modern therapy that could support healthy aging for women.

However, a short-lived backlash followed in the 1970s, when evidence showed that taking estrogen alone increased the risk of endometrial cancer. This led to the addition of progestins for women with an intact uterus, while women who had undergone a hysterectomy continued to use estrogen alone. Throughout the 1970s–1990s, enthusiasm for HRT grew as observational studies suggested additional benefits for cardiovascular health, bone density, mood, and overall wellbeing.

Despite these added benefits, there was still persistent concern about the lack of rigorous randomized trial data supporting long-term safety. In response, the Women’s Health Initiative (WHI) was launched in 1993 with an ambitious trial designed to test whether HRT could prevent cardiovascular disease (given as conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate- MPA). Since investigators wanted to evaluate outcomes like stroke and myocardial infarction, they enrolled an older population, with an average age 63, who were many years past menopause. 

In 2002, early WHI results were released and interpreted as broadly negative. The combined therapy of HRT as CEE plus MPA showed an increased risk of breast cancer, and neither the combined therapy or control therapy of just HRT as CEE demonstrated cardiovascular protection. As a result, prescription rates plummeted. Many women were abruptly taken off hormonal treatments, and clinicians largely stopped offering HRT to new menopausal patients – fearful of causing harm. This meant that an entire generation of women rarely received the option of hormone therapy, and a generation of clinicians received minimal training in its use.

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The Devil Is in the Details

Over time, detailed re-analysis uncovered critical nuances—much of the reported harm reflected the formulations used and the age at which therapy was initiated, not estrogen therapy itself. Subsequent analyses also showed that estrogen-only therapy (used in women without a uterus) actually reduced breast cancer incidence and mortality; and when HRT was started within 10 years of menopause, or before age 60, it lowered all-cause mortality and offered more favorable cardiovascular effects.

Additionally, the evolution in our understanding of hormone therapy similarly involves the type of hormone formulation used. The WHI tested only one synthetic progestin—medroxyprogesterone acetate (MPA)—which is now known to have metabolic and breast tissue effects that differ from micronized progesterone, the bioidentical formulation widely used today. Multiple observational studies and mechanistic data suggest that micronized progesterone is associated with more favorable outcomes, including lower impacts on breast tissue proliferation/growth, a more neutral effect on cardiovascular health, and better sleep and mood benefits. Similarly, the WHI studied conjugated equine estrogens (CEE), a mixture of multiple estrogenic compounds derived from pregnant horses. CEE has a different metabolic and receptor-binding profile than 17β-estradiol, the bioidentical estrogen most commonly prescribed today. Moreover, we now know that estradiol can be delivered transdermally, which results in more stable blood levels and lowers the risk of thromboembolism (blood clotting) and stroke. 

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Today’s Approach

In short, it has become clear that the findings of the WHI were inappropriately generalized to populations and formulations weren’t actually tested by the study. Fortunately, by the 2010s–2020s, a clear scientific consensus began to emerge: timing, age, and formulation are central to understanding HRT’s benefits and risks.  Many providers now prefer transdermal estradiol like gels, patches, and sprays paired with micronized progesterone (pill), a combination supported by physiology and safety data, and one that closely mimics one’s natural hormones.

The FDA’s recent removal of the black box warning reflects alignment between federal health leadership and current scientific evidence. Today, we know that hormone therapy is the most effective treatment for vasomotor symptoms such as hot flashes and night sweats, in addition to meaningfully improving sleep, mood, cognitive function, skin health, and vaginal/urinary symptoms. In fact, local estrogen therapy improves genitourinary symptoms of menopause, such as vaginal dryness and urinary frequency. HRT is also FDA-approved for the prevention of osteoporosis (the weakening of bones, due to loss of mineral density and bone mass).  

Importantly, newer research supports the “timing hypothesis:” starting HRT within 10 years of menopause onset or before age 60 is associated with a more favorable balance of benefits and risks, and may even confer cardiovascular and cognitive advantages.

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Prudence is still required

Of course, HRT is not suitable for everyone. Women with a history of breast cancer, clotting disorders, stroke, or significant cardiovascular risk require individualized evaluation and may need alternatives to systemic hormone therapy. Fortunately, there are highly effective non-hormonal options, such as neurokinin-3 receptor antagonists for hot flashes, SSRIs/SNRIs, and low dose vaginal estrogen for local genitourinary symptoms. Lifestyle strategies, including exercise, nutrition, sleep optimization, and weight management remain essential for bone and cardiovascular health.

A New Era of Menopause Care

The FDA’s decision underscores a crucial point: women deserve accurate, nuanced information to make decisions about their health care. For many, HRT can dramatically improve quality of life and, for those at risk of early menopause or bone loss, offers significant long-term benefits. At the same time, hormone therapy should be used thoughtfully, guided by personalized risk assessment and shared decision making.

This moment offers a chance to reframe the menopause conversation away from outdated caution and toward supportive, evidence-based, individualized care that empowers women to thrive throughout midlife and beyond.