What a month for women's health and menopause awareness! With World Menopause Day on October 8, the Menopause Society Annual Meeting shortly after, and back-to-back women’s health conferences, October highlighted the momentum building in this space. It has certainly been a month of optimism!
At Dama Health, we hope this momentum will translate into actions toward integrated, data-driven care that connects physiology, behavior, and technology to deliver truly personalized care in women's health.
Here’s what stood out for us this month:
✔️ Clarity on MHT and CVD risk: WHI’s latest analysis redefines who benefits from hormone therapy (HT), with age, timing, vascular health, and formulation now central to decision-making.
✔️ Non-hormonal VMS therapy: The FDA’s approval of elinzanetant (Lynkuet™) introduces a second-in-class, hormone-free option for managing vasomotor symptoms, signaling a shift toward targeted neuroendocrine therapeutics.
✔️ MHT & Autoimmune risk: A large database study suggests a small but measurable association between HT and autoimmune disease risk, reinforcing the need for individualized prescribing and ongoing research
Reassessing MHT on CVD Risk.
Last month, a landmark secondary analysis on two randomized clinical trials of HT examined data from ~27,000 postmenopausal women aged 50–79 on conjugated equine estrogens (CEE) alone or CEE + medroxyprogesterone acetate (MPA) against placebo. Researchers assessed whether cardiovascular outcomes differed by age and by the presence of vasomotor symptoms (VMS).
Women aged 50–59 with moderate or severe VMS experienced a 41% reduction in symptoms on CEE or CEE+MPA compared with placebo: a clinically meaningful improvement across both hysterectomy and non-hysterectomy groups. Benefits to VMS were strongest in younger women, but diminished with age, particularly in the CEE + MPA arm.
In those aged 50–59, both regimens relieved VMS without increasing atherosclerotic cardiovascular disease (ASCVD) risk, with low absolute event rates supporting HT as first-line therapy for moderate to severe VMS in early postmenopause. Although vasomotor symptom relief persisted, it was less pronounced in women in their 60s, and ASCVD risk began to rise modestly, then increased substantially after age 69, with up to 200–380 excess ASCVD events per 10,000 person-years.
Therefore, when HT is initiated early (within 10 years of menopause), it appears cardiovascularly neutral, but when started later, risk accumulates.
Mechanistically, several age-related factors likely explain this pattern:
✔️ After about age 60, endothelial function declines and arteries stiffen, increasing susceptibility to prothrombotic and proinflammatory effects of specific hormone therapies.
✔️ When estrogen is reintroduced years after deprivation, it may contribute to destabilization in established atherosclerotic plaques, promoting thrombosis rather than protection.
✔️ Some theories suggest that higher adiposity in older women may blunt estrogen absorption, but even after adjusting for BMI, excess ASCVD risk persisted, implicating vascular aging and formulation effects over body composition.
Importantly, the analysis could not fully separate the effects of chronological aging from the duration of estrogen deprivation before therapy initiation. Additionally, fewer older women had severe VMS or initiated therapy late, making risk estimates less precise (as suggested by wide confidence intervals). Although randomized, this was a post-hoc subgroup analysis by symptom severity and age, suggesting the results are not definitive.
What this means for your practice:
✔️ Timing is critical. HT is safest and most effective when initiated before age 60 or within 10 years of menopause onset. Early initiation supports vascular health, but starting later can shift the balance toward inflammation and thrombosis.
✔️ Formulation choice matters. The cardiovascular risk seen in the two studies analyzed likely reflects the oral, synthetic formulations used. Although direct comparative data are still evolving, modern formulations and transdermal options may offer more favorable risk profiles.
✔️ Individualize and monitor. One-size-fits-all HT is obsolete. Guidelines support ongoing reassessment of HT as cardiovascular and metabolic risks evolve.
In essence, timing, tissue health, and formulation matter. This analysis underscores a broader shift in hormone care from if to when, what, and for whom. In hormone care, the right therapy at the wrong time can change benefit into risk, highlighting where evidence-based personalization must step in. The need for better risk stratification tools that integrate cardiovascular profiles, time since menopause, symptom patterns, lifestyle behaviors, and individual preferences is exactly the kind of precision infrastructure Dama Health is working to make accessible for every clinician.
FDA approves a non-hormonal option for vasomotor symptoms
Just weeks after the re-analysis, the FDA announced approval of Elinzanetant (Lynkuet™), a non-hormonal, once-daily oral treatment for moderate to severe vasomotor symptoms (VMS) such as hot flashes and night sweats. Instead of replenishing estrogen, it blocks neurokinin-1 and neurokinin-3 receptors in the hypothalamus that become hyperactive as estrogen declines during perimenopause. This modulates the body’s internal thermostat, regulating hot flashes, without hormonal exposure.
In clinical trials of women aged 40 to 65, Elinzanetant achieved a 73% reduction in hot flash frequency after 12 weeks, compared with 47% with placebo, with benefits sustained for a full year. Side effects were generally manageable, including drowsiness, fatigue, and headache. However, Elinzanetant has not yet been investigated in combination with HT used for systemic or metabolic changes during (peri)menopause to assess potential additive benefits, differing side effects, or antagonistic interactions.
Even so, this represents a major advance for women who cannot, or choose not to, use hormone therapies.
Elinzanetant joins Fezolinetant (approved 2023) in a new class of neurokinin receptor antagonists, offering hormone-free control of vasomotor symptoms. Ultimately, this approval expands safe and effective options for women who are contraindicated for, or hesitant about, HT!
Should hormone therapy start sooner?
A new analysis presented at The Menopause Society’s 2025 Annual Meeting has reignited a long-standing question in women’s health: Does initiating estrogen therapy during perimenopause alter long-term outcomes? Researchers from Case Western Reserve University and University Hospitals Cleveland conducted a retrospective cohort study using more than 120 million records from the TriNetX Research Network.
Three groups were compared to assess long-term risks of breast cancer, heart attack, and stroke:
✔️ Perimenopausal women who used estrogen therapy for ≥10 years before menopause.
✔️ Postmenopausal women who began estrogen therapy after menopause.
✔️ Postmenopausal women who never used hormones.
Essentially, earlier initiation appeared protective.
While the study supports the “timing hypothesis," that estrogen therapy may be safest and most beneficial when started near menopause onset, before vascular aging and metabolic changes accelerate, not everyone is convinced. Independent experts have cautioned that the data, derived from retrospective, non-randomized records, must be interpreted carefully.
Key considerations from Prof. Annice Mukherjee, Dr. Rosie Cornish, and Dr. Stephanie Faubion suggested the following:
✔️ Access to HT often correlates with higher socioeconomic status, which itself lowers long-term risk. Healthy-user bias is difficult to disentangle.
✔️ Underlying health differences may explain some benefits. Women in the perimenopausal group had to remain disease-free to be included, introducing selection bias.
✔️ While findings suggest potential benefit with earlier initiation, the observational design limits causal inference.
This goes to show that context matters in that cardiovascular and cognitive outcomes following HT use may depend on when therapy begins. However, high-quality, prospective studies are still needed to confirm causality, leaving guidelines unchanged.
Does hormone therapy increase the risk of autoimmune disease?
At the same meeting, new data explored a potential link between HT and autoimmune disease risk. In a large retrospective analysis of nearly 1.8 million postmenopausal women (mean age 60), two matched cohorts, one of HT users and one of nonusers, were followed for up to 10 years after menopause. HT users showed a slightly higher incidence of autoimmune disease, around 27–29% relative risk increase compared with nonusers.
However, experts were quick to contextualize the finding. One hand, they noticed that the absolute increase was modest (≈2%) and varied by condition. On the other hand, causation could not be established with the retrospective, observational nature of this study, especially as the apparent increase in risk is statistically significant but relatively modest in size.
Therefore, the takeaway here is:
✔️ The observed autoimmune risk increase among HT users is small and condition-specific.
✔️ Both timing and context matter: early initiation may optimize benefit–risk balance, but causality remains unproven.
✔️ HT continues to be first-line therapy for menopausal symptoms when individualized to patient risk and preference.
Our focus.
At Dama Health, we’re continuing to build the clinical infrastructure that helps clinical leaders and innovators in precision medicine, women’s health, female longevity, and hormone health (like you!) bring evidence-based personalization into everyday hormone care.
We often speak to healthcare professionals who share the same challenge of struggling to book new patients, and leads visiting their website, but rarely converting into bookings.
Best,
The Dama Health Team