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doi: 10.1016/j.isci.2025.112464

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declining exercise performance Baseline Labs (DUTCH + Standard Panels): Estradiol: Fluctuating wildly (perimenopause) Progesterone: Very low (anovulatory cycles) Cortisol: Elevated evening levels Fasting insulin: 14 IU/mL (insulin resistant) HbA1c: 5.8% (prediabetic range) IGF-1: 156 ng/mL Weight: 178 lbs (goal: 145 lbs) Treatment Protocol: Weeks 1-8: Bioidentical hormone therapy (estradiol patch + oral progesterone) to stabilize hormones, address cortisol with adaptogenic support and sleep optimization Weeks 9-12: Initiate semaglutide 0.25 mg weekly, titrating to 1.0 mg by week 12 Weeks 13-26: Add tesamorelin 2 mg daily to preserve muscle and target visceral fat during weight loss Ongoing: Metformin 500 mg twice daily for insulin sensitivity 26-Week Results: Weight: 148 lbs (-30 lbs total, -16.9%) Body fat: 32% 24% (DEXA) Lean mass: Maintained (actually +1.2 kg gain despite caloric deficit) Fasting insulin: 6 IU/mL (normalized) HbA1c: 5.1% (out of prediabetic range) IGF-1: 223 ng/mL Patient Report: I was terrified Id lose muscle along with the fatId seen friends lose weight on GLP-1s and end up skinny fat. The combination protocol meant I lost fat, kept my muscle, and actually got stronger