New survey finds that most PCPs screen for mild cognitive impairment, but time is an issue, guidelines are few, and low levels of confidence persist.

Exclusive Survey Results: Screening For Cognitive Decline in Primary Care 

Xuezhi Daniel Jiang, MD, PhD, professor of obstetrics and gynecology at the Drexel University College of Medicine.

Hormone Therapy and Autoimmune Disease Risk in Postmenopausal Women, With Xuezhi Daniel Jiang, MD, PhD

Women develop autoimmune diseases at four times the rate of men, and the 

 further increases that risk. It's a pattern every primary care physician and obstetrician-gynecologist recognizes, but the mechanism behind it has remained unclear. Xuezhi (Daniel) Jiang, a professor of obstetrics and gynecology at Drexel University College of Medicine and practicing ob-gyn specializing in menopausal medicine, had a hypothesis: If declining estrogen during menopause increases autoimmune disease risk, could hormone therapy potentially reduce that risk by replacing estrogen? What he found surprised him—and has important implications for how postmenopausal patients should be counseled considering hormone therapy. In this video interview at 

The Menopause Society 2025 Annual Meeting

 in Orlando, Jiang discusses what led him to investigate this connection and how he used a massive global health database to explore the relationship between hormone therapy and autoimmune disease development. In this segment, Jiang covers:

Why women face dramatically higher autoimmune disease risk

How menopausal transition affects autoimmune disease incidence

The rationale for investigating hormone therapy as a potential protective factor

Using the TriNetX database for large-scale research

 Hormone Therapy Linked to Increased Autoimmune Disease Risk

 Clinical Guidance: Counseling Patients Without Creating Hormone Therapy Phobia

Videos

TMS 2025: Jiang explains why he investigated hormone therapy's effect on autoimmune disease risk in postmenopausal women. 

Chapter 3: neffy (epinephrine nasal spray)

Chapter 5: How to prescribe neffy

Chapter 4: Shared Decision Making in Anaphylaxis Care

When to Use Epinephrine in Anaphylaxis

Chapter 2: How to Improve Epinephrine Preparedness

Chapter 1: When to Use Epinephrine in Anaphylaxis

artificial intelligence (AI)-driven intervention 

based on the Diabetes Prevention Program (DPP) achieved outcomes comparable to traditional human-led programs in helping adults with 

 reduce their risk of progressing to diabetes, according to results from the first phase 3 randomized controlled trial to directly compare the 2 approaches.

, found that 31.7% of participants referred to the AI-powered program and 31.9% referred to human coaching met CDC benchmarks for 

 at 12 months, a difference that met the prespecified criterion for noninferiority. Notably, the AI program demonstrated higher rates of both initiation (93.4% vs 82.7%) and completion (63.9% vs 50.3%) compared with traditional programs, according to the results.

"Even beyond diabetes prevention research, there have been very few randomized controlled trials that directly compare AI-based, patient-directed interventions to traditional human standards of care," Nestoras Mathioudakis, MD, MHS, principal investigator and comedical director of the Johns Hopkins Medicine Diabetes Prevention & Education Program, said in a Johns Hopkins statement.

For the parallel-group, pragmatic noninferiority trial, conducted from October 2021 to December 2024, Mathioudakis and colleagues enrolled 368 middle-aged adults (median age 58 years) with prediabetes and overweight or obesity from 2 US clinical sites in Maryland and Pennsylvania. The cohort was 71% women; 61% self-identified as White, 27% as Black, and 6% as Hispanic.

Participants were randomly assigned to receive referral to either a fully automated AI-powered DPP mobile app powered by reinforcement learning algorithms or 1 of 4 CDC-recognized human coach-led programs. A critical component of the study, according to the authors, the research team did not promote engagement after referral, following up only at 6 and 12 months to assess real-world effectiveness.

Personalized push notifications for weight management, physical activity, and nutrition

Active data collection: weight measurements, meal logging

Passive data collection: geolocation, accelerometry

Fully automated, asynchronous delivery via mobile app

Group video conferences (remote delivery due to COVID-19 pandemic)

16 weekly core sessions followed by biweekly to monthly maintenance sessions

The primary composite outcome required maintaining HbA1c below 6.5% throughout the study plus achieving at least one of the following:

 of weekly moderate-to-vigorous physical activity

Clear Noninferiority for the AI-Based Program

The risk difference of −0.2% (one-sided 95% CI, −8.2%) fell well within the noninferiority margin of −15%, demonstrating the AI program was not worse than human coaching. Individual components of the composite endpoint showed similar directional consistency: 16.9% of AI participants versus 20.0% of human-coached participants achieved 5% weight loss, while 12.6% versus 12.4% achieved the combined weight loss and physical activity target.

"The greatest barrier to DPP completion is often initiation, hindered by logistical challenges like scheduling," study cofirst author Benjamin Lalanim now a medical student at Harvard Medical School, said in the statement.

 "So, in addition to clinical outcomes, we were interested in learning whether participants were more likely to start the asynchronous digital program after referral."

When Mathioudakis, Lalanim, et al reviewed engagement data, they observed distinct patterns between groups. Among AI participants who achieved the primary outcome, 74% were program completers compared with 56% in the human-led group.

 “This suggests intervention exposure may play a more central role in the AI-led DPP, which depends on continuous self-directed engagement,” the team wrote. The structured coach-led formats, on the other hand, may allow participants to benefit with less concentrated time investment.

"Unlike human-coached programs, AI-DPPs can be fully automated and always available, extending their reach and making them resistant to factors that may limit access to human DPPs, like staffing shortages," Lalani said. "So, while the black-box nature of AI is a commonly cited barrier to clinical adoption, our study shows that the AI-DPP can provide reliable personalized interventions."

The study's 85.1% retention rate and alignment with expected community-based DPP outcomes (20% achieving 5% weight loss, within the typical 13.5%-35.5% range) support the validity of the findings and the adequacy of program delivery in both arms.

The findings carry particular significance given that only 3% of US adults with prediabetes currently participate in DPPs, despite an estimated 97.6 million Americans having the condition.

 With approximately 1,549 CDC-recognized DPP programs nationwide, which translates to 1 program per 63,000 adults with prediabetes, scalability remains a critical barrier. Further, the authors cite research showing that only 35% of those referred to a DPP ultimately participate. 

Among the study’s limitations, Mathioudakis and fellow investigators acknowledge the unmasked design, use of surrogate rather than diabetes incidence outcomes, and recruitment of motivated volunteers with high baseline physical activity levels and educational attainment from only two sites, limiting generalizability.

As AI continues to evolve, these findings suggest that fully automated behavioral interventions may offer a viable complement, though not necessarily a replacement, for traditional human-coached diabetes prevention programs, the authors said.

Looking ahead, the study team is interested in exploring how the AI app outcomes they observed translate to broader, underserved, real-world patient populations who may not have the time or resources to engage in traditional lifestyle intervention programs. They emphasize that primary care providers, in particular, may consider AI-led DPPs for patients in need of a lifestyle change program, especially those with considerable logistical constraints.

Mathioudakis N, Lalani, B, Abusamaan MS, et al. An AI-powered lifestyle intervention vs human coaching in the Diabetes Prevention Program: a randomized clinical trial. 

 Published online October 27, 2025. doi:10.1001/jama.2025.19563 

AI-powered Diabetes Prevention Program shows similar benefits to those led by people. News release. Johns Hopkins Medicine. October 27, 2025. Accessed October 27, 2025. https://www.hopkinsmedicine.org/news/newsroom/news-releases/2025/10/ai-powered-diabetes-prevention-program-shows-similar-benefits-to-those-led-by-people 

About prediabetes and type 2 diabetes. CDC National Diabetes Prevention Program. Updated May 15, 2024. Accessed October 27, 2025. https://www.cdc.gov/diabetes-prevention/about-prediabetes-type-2/index.html 

Ackermann RT, O’Brien MJ. Evidence and challenges for translation and population impact of the Diabetes Prevention Program. 


2020;20(3):9. doi:10.1007/s11892-020-1293-4

Articles

After 1 year of coaching by the AI app or a DPP-associated coach, reductions in weight and HbA1c and increases in physical activity were equal, an outcome with great promise for scalability. 

AI-Powered Diabetes Prevention Program Intervention Matches Human Coaching in Landmark Trial

A phase 3 clinical trial of estetrol (E4), a naturally occurring estrogen under investigation for the treatment of moderate to severe 

 found no effect on blood pressure after 1 year of treatment, even among women with 

The findings, from the E4COMFORT II trial, were presented by Andrew Kaunitz, MD, of the University of Florida College of Medicine–Jacksonville, and colleagues at the 2025 annual meeting of The Menopause Society, October 21-25. 

E4COMFORT II was a multicenter, 2-part phase 3 study conducted in the United States and Canada that evaluated the efficacy and safety of estetrol 15 mg and 20 mg in postmenopausal 

 All participants had normal baseline blood pressure (equal to or less than 130/80 mm Hg), according to the study abstract.

In the double-blind, placebo-controlled portion of the study, 579 participants were randomly assigned to receive estetrol 15 mg (n=192), estetrol 20 mg (n=193), or placebo (n=194) once daily for 1 year. The open-label safety phase enrolled 430 participants, all of whom received estetrol 20 mg once daily for an additional year.

The investigators analyzed changes in blood pressure from baseline to one year, using analyses of covariance to compare estetrol and placebo groups.

Blood pressure fluctuated only slightly during treatment, with minimal increases observed across all groups, including placebo-treated participants. After 1 year, no statistically significant differences in changes from baseline were found between estetrol-treated participants and those receiving placebo (

 >.05). The absence of blood pressure effects held true regardless of whether women had normal or elevated baseline HbA1c levels.

Cardiometabolic Risk Factors Common at Baseline. 

Although only women with normal baseline blood pressure were enrolled, many participants presented with cardiometabolic risk factors:

HbA1c ≥5.7% (pre-diabetes range): 43.4%

These risk factors were evenly distributed among the treatment groups. Baseline mean blood pressure values were similar, and the presence of higher HbA1c levels did not appear to influence blood pressure outcomes.

A Contrast to Estetrol’s Effects in Younger Women

Estetrol 15 mg is already approved as the estrogenic component in a combined oral contraceptive (COC) with drospirenone 3 mg. That formulation has previously been shown to lower blood pressure in premenopausal women up to age 45 with high-normal baseline levels, by an average of −7.6 mm Hg systolic and −4.0 mm Hg diastolic.

However, the current phase 3 findings in postmenopausal women demonstrate no such blood pressure effect, even at similar or higher estetrol doses and despite the inclusion of women with cardiometabolic risk factors.

The results suggest that estetrol, when used alone for menopausal symptom management, may not alter blood pressure regulation in postmenopausal women, a population in whom cardiovascular safety remains an important consideration in hormone therapy decisions, the authors concluded.

 Phase 3, multicenter, double-blind, placebo-controlled (efficacy) and open-label (safety) trial

: Postmenopausal women aged 40–65 years with normal baseline blood pressure

 Estetrol 15 mg, estetrol 20 mg, or placebo daily for one year

Findings: No significant change in systolic or diastolic blood pressure vs placebo (p>0.05)

 One-year estetrol treatment had no effect on blood pressure, including in women with prediabetes or lipid abnormalities.

Kaunitz A, Kapoor E, Taziaux M, Rezette I, Archer D, Doux. A phase 3 trial of estetrol in postmenopausal women with moderate to severe vasomotor symptoms shows no effect on blood pressure, including in women with cardiovascular risk factors. Poster presented at: The Menopause Society’s 2025 Annual Meeting; October 21-25, 2025; Orlando, FL. Accessed October 24, 2025. 

Lee A, SYed YY. Estetrol/drospirenone: a review in oral contraception. 

2022;82(10):1117–1125. doi: 10.1007/s40265-022-01738-8

The phase 3 E4COMFORT II trial found no impact on BP after 1 year of treatment in postmenopausal women with elevated HbA1c, lipids, and TGs. 

Estetrol Phase 3 Trial Shows No Impact on Postmenopausal BP, Even in Women at High CV Risk

Caroline Mitchell, MD, MPH, Describes Toll of Genitourinary Syndrome of Menopause on QoL

Genitourinary syndrome of menopause affects up to 60% of postmenopausal women, yet it remains one of the most undertreated conditions in women's health, according to Caroline Mitchell, MD, MPH, Associate Professor of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School. 

 spoke with Mitchell during The Menopause Society 2025 Annual Meeting, October 21-25, in Orlando, FL. She explained that, unlike hot flashes that fade with time, GSM symptoms are chronic and progressive, worsening as women move further from their menopausal transition. The impact extends far beyond physical discomfort, affecting sexual function, intimate relationships, and overall quality of life in ways comparable to chronic pulmonary disease.

Despite this significant burden, only about 25% of affected women seek treatment. Many suffer in silence due to embarrassment, misconceptions about treatment safety, or the belief that these symptoms are simply an inevitable part of aging. Meanwhile, primary care clinicians—often the first and only point of contact for these patients—may lack confidence in recognizing and managing GSM, leading to missed opportunities for intervention.

The landscape of GSM treatment has evolved considerably in recent years. Evidence now clearly demonstrates the safety of low-dose vaginal estrogen, even in breast cancer survivors. Research has debunked longstanding myths about sexual activity and vaginal health, while sham-controlled studies have challenged the efficacy of expensive energy-based treatments like fractional laser therapy. Yet translating this evidence into clinical practice remains a challenge, particularly in primary care settings where most women receive their healthcare.

In this interview, Dr. Caroline Mitchell, an expert in menopause and vulvovaginal health, discusses the fundamentals of GSM and its profound impact on women's lives, setting the foundation for understanding why improved recognition and treatment of this condition is critical.

TMS: Half of postmenopausal women suffer from GSM, yet only 25% seek treatment.  Mitchell, an expert in vulvovaginal health, explains the gap and its impact on women. 

Caroline Mitchell, MD, Describes Toll of Genitourinary Syndrome of Menopause on QoL 

The US FDA has approved the investigational agent 

 the first dual neurokinin-1 (NK-1) and neurokinin-3 (NK-3) receptor antagonist, for the treatment of 

The approval marks a long-awaited nonhormonal 

whose hot flashes or night sweats are significant and who are unable or unwilling to use hormone therapy.

“For more than a century, Bayer has been dedicated to pioneering advances in women’s health, and this FDA approval represents a bold step forward – our first hormone-free treatment for alleviating vasomotor symptoms of menopause,”  Christine Roth, executive vice president, global product strategy and commercialization and member of the pharmaceutical leadership team at Bayer,  said in a statement. “There is a need for more individualized approaches to menopause care, and [elinzanetant] addresses a significant gap in treatment options.”

The global population of women experiencing menopause is projected to increase to 1.2 billion by 2030, which translates to 47 million women entering this phase of life each year.

VMS affect up to 60%-80% of women during the menopausal transition, with roughly one-third reporting severe symptoms that persist for years.

 Many women either delay seeking treatment or receive therapies with limited efficacy or tolerability. Many women prefer to pass on traditional hormone replacement therapy (HRT) and for others, the treatment is contraindicated. Current nonhormonal options offer suboptimal relief.

The FDA's approval is based on a phase 3 clinical program (OASIS 1, 2 and 3) which enrolled post-menopausal women aged 40-65 years experiencing moderate to severe VMS. In 

 women received once-daily oral elinzanetant 120 mg or placebo for 26 weeks; key endpoints included mean change in frequency and severity of VMS at weeks 4 and 12. 

OASIS 3, a 52-week double-blind randomized study

 (n = 628), confirmed sustained reductions in VMS frequency along with improvements in sleep disturbances and menopause-related quality of life. A recent meta-analysis found that elinzanetant significantly reduced the frequency of VMS compared with placebo (mean difference –23.1 episodes; 95 % CI –24.2 to –22.0) and improved intensity and sleep disturbance scores.

“These three studies investigated the safety and efficacy of elinzanetant for the treatment of moderate to severe hot flashes due to menopause,” JoAnn Pinkerton, MD, Professor and Director of Midlife Health at UVA Health and Lead Investigator on the OASIS 2 trial, said. “Hot flashes, particularly when severe, can have an impact on women’s daily lives and this approval provides healthcare providers with a new treatment option that can be used first-line for moderate to severe hot flashes due to menopause.”

 to discuss the full read out of results from the OASIS 1 and 2 trials. 

Elinzanetant Outcomes from the OASIS 1 and 2 Phase 3 Trials: A Read Out with Lead Investigator JoAnn Pinkerton, MD

Elinzanetant works by targeting the hypothalamic “thermostat” pathway. With declining estrogen levels, the so-called KNDy neurons (kisspeptin/neurokinin B/dynorphin) in the hypothalamus become hypertrophic and trigger inappropriate activation of thermoregulatory systems via NK-3 and NK-1 receptor signaling. By antagonizing both NK-3 and NK-1, elinzanetant aims to reduce the frequency and severity of VMS by dampening that hyperactivation and modulating associated vasodilatation and heat-sensing neuroactivity.

In contrast, as Pinkerton noted in a separate interview with 

  hormone therapy acts peripherally by replenishing estrogen vs elinzanetant's central recalibration.

Non-Hormonal Therapy for Menopausal VMS: How Does Elinzanetant Differ from HRT?

In terms of safety, the overall elinzanetant profile was favorable across the clinical trial program, with most adverse events being mild to moderate (for example headache, fatigue) and no safety signals that halted development. A recent pooled safety analysis of elinzanetant clinical trials found treatment emergent adverse events comparable between the NK-1/NK-3 antagonist and placebo through 52 weeks of treatment.

“It’s important that women know they have choices for treating moderate to severe hot flashes due to menopause, and today’s approval further expands a woman’s options for treating these symptoms,” Claire Gill, President and Founder of the National Menopause Foundation, added in the Bayer statement.

Bayer AG submitted the New Drug Application for elinzanetant in October 2024, based on the positive OASIS studies. The company said it expects elinzanetant to be available in the US as early as November.

Bayer’s Lynkuet (elinzanetant) approved in the U.S. for treatment of moderate to severe vasomotor symptoms due to menopause. News release. Bayer. October 24, 2025. Accessed October 24, 2025. https://www.bayer.com/media/en-us/bayers-lynkuet-elinzanetant-approved-in-the-us-for-treatment-of-moderate-to-severe-vasomotor-symptoms-due-to-menopause/ 

Global leaders launch declaration on menopause calling World Health Organization and national governments to develop first-ever policies and guidance to support menopausal women. News release. Power Menopause. October 20, 2025. Accessed October 24, 2025. 

Avis NE, Crawford SL, Green R. Vasomotor symptoms across the menopause transition: differences among women. 

. 2018;45(4):629-640. doi:10.1016/j.ogc.2018.07.005 

Thurston RC, Joffe H. Vasomotor symptoms and menopause: findings from the Study of Women's Health across the Nation. 

2011;38(3): 489–501. doi: 10.1016/j.ogc.2011.05.006 

Thurston RC. Vasomotor symptoms: natural history, physiology, and links with cardiovascular health. 

 201821(2):96-100. doi:10.1080/13697137.2018.1430131

The novel once-daily nonhormonal therapy offers a new option to offer women who prefer not to take HRT or for whom it is contraindicated. 