Menopause Treatment Research: Why the Latest Studies Matter
The pace of menopause research has accelerated dramatically since 2020. After decades where the field was dominated by re-analyses of WHI data from women who started hormone therapy in the 1990s, we are now seeing novel drug trials, long-term follow-ups from the major cohort studies, and head-to-head comparisons that actually reflect modern prescribing patterns. The result is a clearer picture than ever of what works, for whom, and under what conditions. This article rounds up the most consequential 2024-2026 studies and explains what their findings mean for your menopause treatment decisions.
The SKYLIGHT extension data, the OASIS trials, the WHI 20-year follow-up, the KEEPS-2 cognitive results, MsFLASH network meta-analyses, and the SWAN cohort’s latest publications all tell a converging story: modern menopause treatment is safer and more effective than the WHI-era scare narratives suggested, and the pipeline of new non-hormonal options is stronger than it has ever been.
SKYLIGHT Extension Data: Fezolinetant After Three Years
The SKYLIGHT 1 and 2 trials established fezolinetant (marketed as Veozah) as the first neurokinin 3 receptor antagonist approved for moderate to severe vasomotor symptoms. The 52-week extension data, published across multiple papers in 2024 and 2025, answered the critical question: does the effect last? The answer is yes. Women who remained on 45 mg of fezolinetant once daily maintained a 60 to 70 percent reduction in hot flash frequency through week 52, with no evidence of tachyphylaxis. The placebo-adjusted reduction was approximately 3.5 fewer moderate to severe hot flashes per day at the end of the extension period.
The safety profile also held up. Liver enzyme monitoring was required during the initial trials after a small number of transaminase elevations were seen in early-phase studies, but the extension data showed no new hepatic safety signals. The most common adverse events remained headache, fatigue, and mild gastrointestinal symptoms, all comparable to placebo rates after the first four weeks. For women who cannot or will not take hormones, fezolinetant now has the strongest long-term safety dataset of any non-hormonal vasomotor treatment. A detailed review of this option is available in our article on Veozah for hot flashes.
OASIS Trials: Elinzanetant Enters the Picture
The OASIS 1 and 2 trials, published in The Lancet in 2024, tested elinzanetant, a dual neurokinin 1 and 3 receptor antagonist developed by Bayer. Where fezolinetant blocks only NK3 receptors, elinzanetant blocks both NK1 and NK3, which theoretically could provide broader symptom relief. The phase 3 results showed elinzanetant reduced hot flash frequency by approximately 65 percent at 12 weeks compared to 30 percent with placebo, with statistically significant improvements in sleep disturbance and menopause-related quality of life as measured by the MENQOL questionnaire. A separate OASIS 3 study, presented at the 2025 North American Menopause Society annual meeting, confirmed the 52-week safety profile and showed no withdrawal syndrome upon discontinuation. Unlike the abrupt symptom return seen with some GnRH modulators, women who stopped elinzanetant experienced a gradual return to baseline VMS frequency over four to six weeks. The drug received FDA approval in early 2026, giving women a second non-hormonal neurokinin option alongside fezolinetant.
The practical difference between the two drugs matters. Fezolinetant is a single receptor blocker and has the advantage of more long-term safety data. Elinzanetant blocks two receptors and may offer marginally better sleep benefits, but the data comparing the two head to head does not yet exist. Neil M. Schulman, the lead investigator for the OASIS program, told Endocrine News in 2025 that “the ideal candidate profile for elinzanetant versus fezolinetant will become clearer once we have real-world evidence.” For a full breakdown of non-hormonal menopause treatment options, including both NK3 antagonists, our dedicated guide covers the comparison.
WHI 20-Year Follow-Up: The Final Word?
In 2024, the WHI investigators published what may be the final comprehensive follow-up of the hormone therapy trials, covering a median 20 years of cumulative data. The findings were nuanced but broadly reassuring. In the estrogen-alone trial (women with prior hysterectomy), all-cause mortality was 11 percent lower in the estrogen group than placebo over the full follow-up period, driven largely by reductions in breast cancer mortality and cardiovascular death. In the estrogen-plus-progestin trial, the all-cause mortality signal was neutral, meaning no net harm and no net benefit over 20 years.
The breast cancer findings bear specific attention. The WHI estrogen-plus-progestin arm showed a statistically significant increase in breast cancer incidence during the intervention phase (hazard ratio 1.24), consistent with the 2002 results. But that excess risk diminished after the trial ended and was no longer statistically significant at the 20-year mark. In the estrogen-alone arm, breast cancer incidence remained reduced throughout follow-up, with a hazard ratio of 0.78 at 20 years. Dr. JoAnn Manson, the principal investigator of the WHI, summarized the findings in JAMA: “The long-term data support the safety of hormone therapy initiated in early menopause for women with bothersome symptoms, and they should reassure women that the risks have been overstated for two decades.”
KEEPS-2 Cognitive Results: What Hormones Do to Your Brain
The Kronos Early Estrogen Prevention Study (KEEPS) has been running since 2005, and the KEEPS-2 cognitive results were published in Menopause in 2025. The study randomized recently postmenopausal women aged 42 to 58 to oral conjugated equine estrogens, transdermal estradiol, or placebo, all with cyclic progesterone. The cognitive battery tested memory, executive function, verbal fluency, and processing speed at baseline, 18 months, and 36 months.
The headline finding: neither oral CEE nor transdermal estradiol had a statistically significant effect on cognitive decline compared to placebo over three years. But a pre-specified subgroup analysis revealed a signal worth watching. Women who initiated treatment within three years of their final menstrual period showed a trend toward better verbal memory scores, while those who started later (four to six years postmenopause) did not. This aligns with the timing hypothesis and suggests that the brain may have a specific window for hormone responsiveness, much like the cardiovascular system. The KEEPS-2 results also confirmed that transdermal estradiol had no adverse cognitive effects at any initiation timing, which matters for the many women who prefer a transdermal route. More on menopause brain fog and what the research shows.
MsFLASH Network Meta-Analyses: Ranking What Works Best
The Menopause Strategies Finding Lasting Answers for Symptoms and Health (MsFLASH) network published a pair of network meta-analyses in 2025 that provided the most comprehensive ranking of vasomotor symptom treatments available. The analyses, which pooled data from 45 randomized trials involving over 12,000 women, compared hormone therapy, SSRIs, SNRIs, gabapentin, pregabalin, fezolinetant, clonidine, and non-pharmacologic interventions.
The results placed hormone therapy at the top for hot flash reduction — approximately 80 percent reduction in frequency compared to placebo — followed by fezolinetant and elinzanetant at approximately 65 percent. SSRIs and SNRIs clustered around 40 to 50 percent reduction, while gabapentin achieved approximately 45 percent but with higher rates of dizziness and sedation. Non-pharmacologic interventions including cognitive behavioral therapy and clinical hypnosis showed modest but reproducible effects of 20 to 30 percent. The MsFLASH meta-analyses also confirmed what clinicians had suspected: the placebo effect in VMS trials is consistently large, averaging 25 to 35 percent reduction in frequency, which means treatment effects need to clear a high bar to be clinically meaningful.
SWAN 2025–2026: The Longest Running Picture of Women’s Midlife Health
The Study of Women’s Health Across the Nation (SWAN) has followed more than 3,300 women through the menopausal transition since 1994. The 2025 and 2026 publications from SWAN continue to generate insights that no clinical trial can match, because SWAN tracks real women across decades, not selected volunteers in controlled conditions for a few years.
A 2025 SWAN paper in the Journal of Clinical Endocrinology and Metabolism showed that women who used MHT for more than five years had lower rates of coronary artery calcium progression than never-users, but only when MHT was initiated within five years of menopause. A 2026 SWAN publication on body composition found that MHT use was associated with approximately 2.5 percent less visceral adipose tissue accumulation per year compared to non-use — a modest but metabolically meaningful difference given that visceral fat is an independent risk factor for cardiovascular disease and type 2 diabetes. SWAN principal investigator Dr. Siobán Harlow of the University of Michigan noted in a 2026 interview that “the SWAN data consistently show that the benefits of hormone therapy are concentrated in women who start early, and those benefits extend beyond symptom relief to metabolic health.”
What’s Coming Next in the Pipeline
Beyond the drugs already on the market, the development pipeline looks robust. Several phase 2 trials are underway evaluating additional NK3 receptor antagonists with once-weekly dosing rather than daily. A phase 2 trial of a combination estradiol-NK3 antagonist patch is in early recruitment, which would be the first hormonal-nonhormonal combination product. The first head-to-head trial of fezolinetant versus elinzanetant, expected to begin enrollment in late 2026, will answer the question women and clinicians have been asking since the second drug was approved.
On the hormone therapy front, a new ultra-low-dose transdermal estradiol patch (0.014 mg/day) received FDA approval in 2025, offering a microdosing option for women who are particularly risk-averse or who have experienced side effects at standard doses. The Women’s Preventive Services Initiative is also evaluating whether the Affordable Care Act’s mandate for no-copay preventive services should explicitly include menopause care, which could dramatically change access for the estimated 18 million uninsured or underinsured perimenopausal women in the US. The menopause treatment hierarchy based on the latest evidence continues to evolve as these trials report their results.
Bottom line: The evidence base for menopause treatment is stronger in 2026 than it has ever been. The WHI story has been properly contextualized. New non-hormonal options give women genuine alternatives. And the long-term follow-up of major cohorts consistently shows that modern, appropriately timed treatment outcomes are excellent. If a clinician tells you “there’s no evidence for that,” check the publication date of whatever study they are citing. The evidence moved.