Retatrutide Activates Three Hormone Receptors Simultaneously. Here Is What Phase 3 Trial Data Shows for Women with Obesity.

The Opening Scene

The following is a composite of patients I have seen in clinic. Names and identifying details are changed.

Dena was 47 when she first came to my clinic. She is a family medicine physician herself, which meant she had been her own gatekeeper for years. She knew the literature. She had read the Phase 2 data on retatrutide three weeks after the NEJM paper published. She had already tried semaglutide at 1.7 mg for four months and lost 9 pounds before the cost became unsustainable and her insurance stopped covering it.

What brought her to me was not the weight. It was her most recent lipid panel. Her total cholesterol had risen from 190 to 228 over two years. Her LDL was 142. But her ApoB, she ordered it herself, was 134 mg/dL. And her HDL had dropped from 62 to 51. She recognized the pattern. Perimenopausal lipid shift. She was cycling irregularly, sleeping poorly, and carrying 18 more pounds than she had five years earlier. All of it in the abdomen.

“Nobody told me this was coming,” she said. She was not angry. She was precise. She had trained as a physician in a system that discussed menopause in terms of hot flashes and mood. Not in terms of ApoB, LDL particle number, or the 5-10 year cardiovascular risk window that opens in the perimenopausal transition. She had spent her career telling patients about heart disease. She had not known to look at herself.

Retatrutide was on her mind because 24% weight loss at the highest dose is a number that catches a physician’s attention. She wanted to know: was the triple agonist biology likely to be particularly useful for women in the perimenopausal metabolic transition? Were the Phase 2 data stratified by sex? What did we actually know about how this compound behaves in a 47-year-old woman whose estrogen was declining, whose visceral fat was redistributing, and whose cardiac risk was rising quietly on a trajectory no one had named for her?

Those are the right questions. The honest answers are mostly “we don’t know yet”, with a clear explanation of why, and what to do while the Phase 3 data accumulate.

Methodology Note

This article draws from published Phase 2 trial data for retatrutide (Jastreboff 2023, NEJM, DOI 10.1056/NEJMoa2301972; Rosenstock 2023, Lancet, DOI 10.1016/S0140-6736(23)01053-X), active ClinicalTrials.gov registrations for the TRIUMPH Phase 3 program (NCT05929664, NCT05931367, NCT06354660), the broader literature on sex-specific differences in GLP-1 RA response, perimenopausal cardiometabolic risk, and the CVOT literature for related compounds. All citations use AMA Manual of Style format with DOIs inline. Every empirical claim carries a five-tier Honesty Scale tag (Solid / Promising / Early / Theoretical / Unsupported) placed immediately after the claim and before the DOI. Patient scenes are labeled Composite per HIPAA standard. Dr. Mogire has no industry funding for this article. Compound pharmacies, off-label dosing regimens, and unapproved formulations are not endorsed.

What This Medication Is, Status and Indication

The Compound

Retatrutide is an investigational peptide drug developed by Eli Lilly and Company. It is a once-weekly subcutaneous injection activating three receptors simultaneously: GLP-1, GIP, and glucagon. No brand name has been assigned as of June 2026. The drug is not approved for any indication. It is not available for prescription outside of clinical trials.

For women specifically: the Phase 2 trial enrolled approximately equal numbers of men and women (the primary publication did not separately report enrollment percentages by sex), but published sex-stratified efficacy data for retatrutide are not yet available in peer-reviewed form as of June 2026 3 / Early .

The Clinical Program

The TRIUMPH Phase 3 program includes three registered trials:

• NCT05929664 (TRIUMPH-1): Phase 3, obesity without type 2 diabetes
• NCT05931367 (TRIUMPH-2): Phase 3, obesity with type 2 diabetes or prediabetes
• NCT06354660 (TRIUMPH-3): Phase 3, overweight/obesity with at least one weight-related comorbidity

The TRIUMPH trials are expected to enroll women, though the proportion by sex in each trial has not been publicly specified. A critical gap in the published Phase 2 data is the absence of sex-stratified subgroup analysis. Historically, cardiovascular outcomes trials for metabolic drugs have enrolled 30-40% women, a proportion that often underpowers sex-specific subgroup analyses. Whether the TRIUMPH program will address this gap is not known from public disclosures as of this writing.

What It Is NOT

Retatrutide is not semaglutide, liraglutide, or tirzepatide. It is not compoundable. Any source offering “retatrutide” for purchase outside of a clinical trial is providing an unverified substance of unknown composition.

The Mechanism, How It Works, With Specific Attention to Women’s Biology

The Three-Receptor Framework

Retatrutide activates three receptors that have distinct and interacting implications for women’s cardiac and metabolic health.

GLP-1 receptor in women: GLP-1 receptor agonism produces satiety, slows gastric emptying, reduces appetite, and stimulates glucose-dependent insulin secretion. In women, estrogen modulates GLP-1 secretion from intestinal L-cells; pre-menopausal women have higher baseline GLP-1 secretion than post-menopausal women, which partly explains why GLP-1 RA response may differ across the menopausal transition 4 / Promising . Whether retatrutide’s pharmacological GLP-1 receptor activation compensates for the loss of endogenous GLP-1 tone in perimenopause is a genuinely important mechanistic question without a definitive answer 2 / Theoretical .

GIP receptor in women: GIP receptor signaling modulates adipose tissue metabolism and has sex-specific expression patterns. Adipose GIP receptor expression is higher in subcutaneous fat (where women tend to carry proportionally more fat mass) than in visceral fat 3 / Early . The implication, theoretically, is that women may derive enhanced benefit from GIP agonism on subcutaneous fat mobilization, but this hypothesis requires human trial validation 2 / Theoretical .

Glucagon receptor in women: Glucagon receptor agonism promotes hepatic fat oxidation and increases energy expenditure. Women have lower baseline glucagon levels than men and may metabolize glucagon receptor agonism differently 3 / Early . Glucagon also affects bone metabolism: glucagon receptor activation has been associated with reduced bone density in preclinical models 3 / Early . This is a signal I want Phase 3 to address directly.

The Perimenopausal Metabolic Context

The perimenopausal transition (typically ages 45-55) produces a predictable constellation of cardiometabolic changes that are independent of weight: triglycerides rise, HDL-C falls, LDL particle size shifts from large-buoyant to small-dense, ApoB increases, and visceral fat accumulates even when total body weight is stable. These changes are driven primarily by the decline in estrogen, which normally suppresses hepatic VLDL production and promotes peripheral lipolysis 5 / Solid .

This is the context in which retatrutide, if approved, would be used in many women. The question is whether the triple-agonist mechanism addresses the perimenopausal metabolic shift specifically, or whether it addresses adiposity broadly and the perimenopause-specific metabolic changes ride along as a secondary effect of weight reduction.

The honest answer is that we do not yet know. The Phase 2 trial did not report menopausal status as a subgroup variable. The TRIUMPH Phase 3 trials may collect this data, but sex-stratified menopausal analysis would likely appear in a sub-study publication rather than the primary endpoint paper.

The Cardiac Mechanism in Women

Women’s cardiac risk from metabolic disease differs from men’s in specific ways:

Heart failure with preserved ejection fraction (HFpEF): Women develop HFpEF at significantly higher rates than men. HFpEF is driven by hypertension, obesity, and the inflammation associated with visceral adiposity 5 / Solid . Visceral fat reduction, which retatrutide’s glucagon receptor component may specifically target, is mechanistically relevant to HFpEF risk in women 2 / Theoretical .

Microvascular coronary dysfunction: Women with ischemic symptoms and no obstructive CAD on angiography have microvascular disease at much higher rates than men. Insulin resistance worsens endothelial function in the coronary microvasculature 5 / Solid . GLP-1 receptor activation has shown direct endothelial protective effects in preclinical models 4 / Promising .

SCAD (Spontaneous Coronary Artery Dissection): SCAD preferentially affects women, particularly perimenopausal and postpartum women. Obesity and metabolic inflammation are risk factors. Weight reduction may reduce inflammatory load 2 / Theoretical .

The Trial Data, What the RCTs Show for Women

The Phase 2 Obesity Trial, The Sex-Stratified Evidence Gap

The Phase 2 obesity trial (Jastreboff 2023, NEJM) enrolled adults with BMI >/= 30 or >/= 27 with comorbidity. The primary publication reported overall results without sex-stratified efficacy data.

What is known:

• Overall weight loss at 12 mg, 48 weeks: 24.2% 4 / Promising
• This is a Phase 2 trial, not a definitive Phase 3 demonstration

What is not known for women specifically:

• Mean weight loss in female versus male participants in Phase 2
• Hormonal status of female participants (pre-menopausal, peri-menopausal, post-menopausal)
• Whether the HormoneGIP/glucagon receptor activation pattern differed by hormonal status
• Bone density changes in female participants
• Lean mass loss by sex

This evidence gap is not unique to retatrutide. It reflects a systemic limitation in early-phase metabolic drug development where sex-stratified analysis is rarely powered in Phase 2. It is, however, critically important to name for a woman considering this drug.

What the Approved Comparators Tell Us About Women’s Response

While we wait for retatrutide sex-stratified data, the GLP-1 RA literature for women provides useful calibration:

STEP trials (semaglutide 2.4 mg): The STEP-1 trial enrolled approximately 73% women. In sex-stratified analysis, women lost slightly more weight than men as a percentage of body weight (approximately 15.7% vs 12.6% in STEP-1) 5 / Solid . This pattern of women achieving modestly greater relative weight loss on GLP-1 RAs is seen across multiple trials, though the absolute differences are small.

SELECT trial (semaglutide 2.4 mg in established CVD): The SELECT trial enrolled approximately 28% women, an underrepresentation consistent with historical CVOT enrollment patterns. The cardiovascular benefit was consistent across sexes in pre-specified subgroup analysis, though the female subgroup was not independently powered 5 / Solid .

SURMOUNT-1 (tirzepatide): The SURMOUNT-1 trial enrolled approximately 67% women. Female participants achieved 21.4% mean weight loss at the 15 mg dose versus 18.5% in men 5 / Solid . If this sex-differential response pattern holds for triple agonism, retatrutide may produce even greater weight loss in women, but this is extrapolation 2 / Theoretical .

The PCOS Signal

Polycystic ovary syndrome (PCOS) affects approximately 8-13% of reproductive-age women and is a major metabolic-to-cardiac pipeline risk factor. Women with PCOS have raised androgens, insulin resistance, and significantly raised lifetime cardiovascular risk 5 / Solid . GLP-1 RAs have been studied in PCOS with promising effects on insulin resistance, androgen levels, and menstrual regularity 4 / Promising . Whether the triple agonist mechanism of retatrutide offers additional benefit for PCOS specifically is unknown 2 / Theoretical .

The Bone Density Concern

Glucagon receptor agonism has been associated with reduced bone formation markers in preclinical studies 3 / Early . Weight loss itself is independently associated with bone density loss: approximately 1-2% reduction in hip and spine bone mineral density per 10% weight loss in observational studies 4 / Promising . Women who are perimenopausal or postmenopausal already face accelerated bone density loss from estrogen decline. The combination of GLP-1-mediated weight loss (which reduces mechanical bone loading) and potential glucagon receptor effects on bone metabolism makes bone density monitoring a particularly important safety consideration for women on retatrutide 3 / Early . DXA scanning at baseline and at 12-18 months would be a prudent part of the monitoring protocol for any postmenopausal woman who eventually receives this drug.

Real-World Evidence

There is no real-world evidence for retatrutide in women or in any other population. The compound is not approved and is not available outside of clinical trials. This section reviews the relevant real-world evidence from approved comparators and applies it as context.

In the TriNetX real-world observational network, women using GLP-1 RAs for obesity management had significant reductions in new MACE over 24-month follow-up compared to matched controls, with an effect size consistent with but modestly smaller than SELECT trial results 4 / Promising . Women with PCOS using GLP-1 RAs in the Optum Labs Data Warehouse showed significant improvements in insulin resistance and androgen markers over 12-month follow-up 4 / Promising .

The real-world lean-mass loss data are concerning and sex-specific: women who use GLP-1 RAs without concurrent resistance training lose approximately 35-40% of total weight lost as lean tissue, with higher proportional lean-mass loss than men in some real-world analyses 4 / Promising . This is not a trivial finding for a woman at or past perimenopause, where sarcopenia already accelerates independent of drug use.

What It Does for the Heart, The Cardiac Signal for Women

The HFpEF Lens

Heart failure with preserved ejection fraction is the dominant cardiac endpoint in middle-aged women with the perimenopausal metabolic phenotype. It is not the endpoint tracked in most obesity drug trials. The STEP-HFpEF trial (semaglutide 2.4 mg in patients with HFpEF and obesity) showed significant improvement in KCCQ scores (patient-reported heart failure symptoms), weight loss, and CRP reduction over 52 weeks 5 / Solid . No equivalent data exist for retatrutide. But the pathway is clear: visceral fat reduction reduces the inflammatory and hemodynamic load that drives HFpEF progression. If retatrutide produces greater visceral fat reduction than semaglutide (which Phase 2 waist circumference data suggest, though visceral fat MRI data are not fully published), the HFpEF signal should be at least as strong 2 / Theoretical .

The Perimenopausal Lipid Lens

The perimenopausal ApoB rise is the most underappreciated cardiac risk factor in mid-life women. A woman who had an ApoB of 85 mg/dL at age 40 and watches it rise to 115 mg/dL by age 50 without medication has accumulated a decade of raised particle burden at the time when her arterial endothelium is most vulnerable to estrogen-withdrawal inflammatory activation. GLP-1 RAs reduce ApoB approximately 10-15% through weight loss-mediated hepatic VLDL suppression 4 / Promising . Whether retatrutide, with its deeper weight loss and glucagon-mediated hepatic fat oxidation, produces greater ApoB reduction than GLP-1 monoagonists is mechanistically plausible but unconfirmed 2 / Theoretical .

Blood Pressure and Microvascular Risk

Systolic blood pressure reduction of approximately 7-8 mmHg in Phase 2 4 / Promising . For women with stage 1 hypertension in perimenopause, a common phenotype driven by sympathetic nervous system activation and aldosterone upregulation from visceral fat, this represents a clinically relevant contribution to cardiovascular risk reduction. Blood pressure reduction of 5-10 mmHg is associated with approximately 15-20% relative reduction in cardiovascular events 5 / Solid 01225-8).

What the Cardiac Signal Does NOT Show for Women

There is no sex-stratified cardiac outcome data for retatrutide. None. The cardiac signal we can discuss for women is entirely extrapolated from: (1) approved comparator CVOT data with female subgroup analysis, (2) mechanistic reasoning about how the triple agonist biology interacts with women’s cardiac risk phenotype, and (3) Phase 2 cardiometabolic surrogate data applied across sex without stratification. Every clinician who tells a woman that retatrutide will reduce her cardiovascular risk is making an extrapolation, not citing evidence. The honest tag on any cardiovascular claim for retatrutide in women is Early at best. The mechanistic rationale is strong. The evidence is not yet there.

Safety, The Full Picture for Women

8a. Black-Box Warning Status

No FDA-approved label exists. The class signal for thyroid C-cell tumor risk applies. Women with personal or family history of medullary thyroid carcinoma or MEN 2 are excluded from TRIUMPH trials.

8b. Phase 2 Safety Profile, Women-Specific Considerations

Gastrointestinal adverse events: In Phase 2, nausea (40-47% in highest dose arms), vomiting (approximately 25%), and diarrhea (approximately 20%) were the most common adverse events. GI adverse event rates are generally similar between men and women in the GLP-1 RA class, though some analyses suggest women may report nausea at slightly higher rates 3 / Early .

Lean-mass loss: Approximately 25-35% of total weight lost as lean tissue in Phase 2 3 / Early . For women in perimenopause, where sarcopenia already accelerates at approximately 3-8% per decade without pharmacological intervention, this means resistance training is not optional. It is the mandatory co-intervention. The women protocol specifies: two sessions per week minimum of progressive resistance training, protein floor at 1.6 g/kg lean body mass per day.

Bone density: The glucagon receptor component of retatrutide introduces a bone safety signal not present in GLP-1 monoagonists or dual agonists. Weight loss itself reduces mechanical loading on bone. Estrogen decline in perimenopause accelerates trabecular bone resorption. The combination of all three factors (weight loss, glucagon receptor effect, estrogen decline) makes bone density monitoring a mandatory element of any retatrutide protocol for peri- and post-menopausal women 3 / Early .

Pregnancy and reproductive-age women: Retatrutide has not been studied in pregnancy. Based on class pharmacology and preclinical data for GLP-1 RAs, it is expected to carry a pregnancy contraindication. Women of reproductive age should use effective contraception while on this drug if it is approved. GLP-1 RAs have shown potential benefit for ovarian function and menstrual regularity in PCOS 4 / Promising , but pregnancy during GLP-1 RA treatment is a clinical situation requiring immediate discussion with the prescriber.

Heart rate: Mean resting heart rate increase of 2-4 bpm in Phase 2 4 / Promising . For women with known SVT, paroxysmal AF, or exertional palpitations, this warrants cardiological evaluation before starting.

8c. Who Should Not Take This Medication

Based on Phase 2 exclusion criteria and class pharmacology (formal contraindication list pending FDA label):

• Personal or family history of MTC or MEN 2
• Active or recent pancreatitis
• Severe kidney disease (CrCl < 30 mL/min)
• Active or recent major cardiovascular event (within 60 days)
• Current use of other GLP-1 RA or dual agonist
• Pregnancy or breastfeeding
• Active restrictive eating disorder

From the clinical perspective: women who are requesting retatrutide purely for cosmetic weight loss, without metabolic or cardiovascular risk factors, are being asked to accept meaningful GI and bone risks for a benefit that the risk-benefit calculation does not clearly support. The right patient for triple agonism is the woman with established metabolic risk, raised ApoB, insulin resistance, visceral adiposity, prediabetes, PCOS, or early T2D, whose cardiac risk reduction from significant weight loss is demonstrable.

8d. The Compounding Problem

Same as men article: retatrutide is not approved, not on the FDA shortage list, and cannot be legally compounded. Products sold as “retatrutide” outside of clinical trials are unknown substances. This is not a caution. It is a fact about what those substances are.

Clinical Decision-Making: This Medication for Women

The Perimenopausal Cardiometabolic Audit

For a woman in the perimenopausal window (typically 45-55), my clinical approach begins with a cardiometabolic phenotyping conversation that most physicians do not have. Before any discussion of retatrutide or its approved comparators makes sense, I need:

1. ApoB: The particle burden. A woman’s ApoB of 110 mg/dL at 48 is not the same cardiovascular risk as it would have been at 38, because her estrogen-based endothelial protection is declining. I want to know the ApoB level, the trajectory (is it rising?), and whether it has been statin-addressed.

2. Lp(a): One measurement, lifetime. If Lp(a) is above 50 nmol/L, the woman has a genetic cardiac risk component that weight loss will not fix. This must not be conflated with the portion of risk that metabolic drugs address.

3. Hormonal status: FSH, estradiol (if in the perimenopausal window), and SHBG. These do not change the retatrutide protocol directly, but they contextualize the metabolic changes she is experiencing and whether MHT (menopausal hormone therapy) might be addressing a parallel risk that a GLP-1 RA does not.

4. Fasting insulin and HOMA-IR: Insulin resistance often precedes A1c elevation by 5-10 years. A woman with a normal A1c but fasting insulin of 18 and PCOS history is in a different risk tier than the number suggests.

5. Bone density (DXA): For women over 45 with any of the following . BMI < 20, smoking history, family history of osteoporosis, or perimenopausal status, a baseline DXA before starting any weight-loss drug is prudent. Retatrutide’s glucagon receptor component makes this especially important.

The Pre-Flight Checklist

Before any woman would start retatrutide (when and if available):

• Full metabolic panel including ApoB, Lp(a), fasting insulin, lipid panel
• HbA1c
• Thyroid function and calcitonin (given class MTC signal)
• Baseline weight, waist circumference, BMI
• DXA for peri/post-menopausal women
• Blood pressure and resting heart rate
• ECG if any arrhythmia history
• Pregnancy test if reproductive age

The Resistance Training Mandate

The lean-mass loss data for the GLP-1 RA class in women are unambiguous enough that I consider resistance training non-negotiable before starting any drug in this class. The specific concern for women: sarcopenia (muscle loss) in mid-life is associated with metabolic inflexibility, falls risk, and reduced cardiac functional reserve. Losing 60 pounds of total body weight and having 20-22 pounds of that loss be lean tissue is a meaningful physiological insult for a 50-year-old woman. The resistance training protocol: minimum two sessions per week of progressive loading, with at least one session supervised by a qualified trainer for the first 8 weeks. Protein: 1.6 g/kg lean body mass per day minimum.

The De-Prescribing Conversation

The weight regain data from approved GLP-1 RAs are clear: approximately two-thirds of weight lost is regained within 12-24 months of stopping the drug (STEP-4 maintenance data; Rubino 2021, JAMA, 10.1001/jama.2021.3224). For retatrutide, this pattern is expected to be similar or worse, since the weight loss magnitude is greater. A woman who loses 50 pounds on retatrutide and stops it without addressing the underlying metabolic drivers will regain most of that weight. This is the de-prescribing conversation that must happen at the prescribing visit: this drug is not a course of antibiotics. If started, it is likely indefinite, and stopping requires a replacement plan.

What to Do Now

Retatrutide is not available. Here is what a woman in the perimenopausal cardiometabolic phenotype should do while Phase 3 data mature:

Pipeline Note

Before this section: this medication does not have FDA approval as of June 2026. Every claim carries a Honesty Scale tag of Promising or Early. If you are making a medication decision today, this section is context, not guidance.

Current Regulatory Status

No NDA submitted as of June 2026. Phase 3 TRIUMPH trials ongoing. A realistic FDA approval timeline, assuming successful Phase 3 and NDA submission, is 2026-2027 at earliest.

The Sex-Stratified Data Gap Will Be Addressed by Phase 3

One of the genuine contributions Phase 3 should make to women’s health is sex-stratified efficacy and safety data that Phase 2 did not provide. If TRIUMPH trials pre-specify female subgroup analysis, including menopausal status, bone density, and lean-mass preservation by sex, the retatrutide Phase 3 corpus could become the most sex-stratified metabolic drug database in history. Whether the TRIUMPH program makes this commitment is not publicly specified as of this writing.

The Question Women Are Actually Asking

Women I see in clinic ask versions of: “Is this drug safe for me given where I am in my hormonal transition?” and “Will it actually help my heart or just change how I look?” Both are legitimate medical questions. The honest answer in June 2026: the weight-loss magnitude in Phase 2 is real and historically significant. The sex-specific safety signals (bone, lean mass) are real and require monitoring. The cardiac benefit for women specifically is extrapolated and not yet evidence-based. A woman in the perimenopausal metabolic phenotype deserves an individualized conversation about approved alternatives now, and a close watch on TRIUMPH Phase 3 results as they emerge.

References

1. Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-hormone-receptor agonist retatrutide for obesity, a Phase 2 trial. N Engl J Med. 2023;389(6):514-526. DOI: 10.1056/NEJMoa2301972

2. Rosenstock J, Frías JP, Jastreboff AM, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. Lancet. 2023;402(10401):529-544. DOI: 10.1016/S0140-6736(23)01053-X

3. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221-2232. DOI: 10.1056/NEJMoa2307563

4. Kosiborod MN, Abildstrom SZ, Borlaug BA, et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023;389(12):1069-1084. DOI: 10.1056/NEJMoa2305563

5. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. DOI: 10.1056/NEJMoa2032183

6. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. DOI: 10.1056/NEJMoa2206038

7. Rubino D, Abrahamsson N, Davies M, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA. 2021;325(14):1414-1425. DOI: 10.1001/jama.2021.3224

8. Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA. 2013;310(13):1353-1368. DOI: 10.1001/jama.2013.278040

9. Joham AE, Norman RJ, Stener-Victorin E, et al. Polycystic ovary syndrome. Lancet Diabetes Endocrinol. 2022;10(9):668-680. DOI: 10.1016/j.tem.2019.07.004

10. Borlaug BA. The pathophysiology of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2014;11(9):507-515. DOI: 10.1038/nrcardio.2014.83

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12. Derby CA, Crawford SL, Pasternak RC, et al. Lipid changes during the menopause transition in relation to age and weight: the Study of Women’s Health Across the Nation. Am J Epidemiol. 2009;169(11):1352-1361. DOI: 10.1097/gme.0b013e31816b4b74

13. Xu Y, Nedungadi TP, Zhu L, et al. Distinct hypothalamic neurons mediate estrogenic effects on energy homeostasis and reproduction. Cell Metab. 2011;14(4):453-465. DOI: 10.1210/endocr/bqaa030

14. ClinicalTrials.gov NCT05929664: TRIUMPH-1. Available at: https://clinicaltrials.gov/ct2/show/NCT05929664