@HelloRapa and @Forever29 it seems like the information below likely explains what you are seeing - would you agree? And its nothing to worry about - the lower AMH is expected and shows that the Rapamycin is helping.
Note - I just queried Google Gemini Pro with the following prompt (you can tweak it yourself and run it on other AI systems:
Role: You are a Longevity Research Analyst and OBGYN. Your audience consists of scientifically literate longevity biohackers, clinicians, and professionals.
Task: Identify how rapamycin impacts women’s AMH levels if she was taking rapamycin on a pulsatile basis once every week 6mg?
Gemini Response:
Executive Summary
For a woman taking a pulsatile dose of rapamycin (e.g., 6 mg once weekly), the expected impact on Anti-Müllerian Hormone (AMH) levels is clinically paradoxical: AMH levels will likely decrease or appear artificially suppressed during active treatment, even though the underlying true ovarian reserve is being preserved. Clinicians and biohackers monitoring ovarian health must understand that during mTOR inhibition, a drop in AMH is a feature of the drug’s mechanism of action, not a symptom of accelerated ovarian aging.
In a clinical setting, a woman taking a 6 mg once-weekly pulsatile dose of rapamycin will likely present with suppressed or artificially decreased serum Anti-Müllerian Hormone (AMH) levels during the active treatment phase. For the prescribing OBGYN or longevity clinician, it is critical to understand that this decline is an intended pharmacokinetic feature of systemic mTOR inhibition, rather than an indicator of accelerated ovarian senescence.
Mechanism of Action: The AMH Paradox
To understand why AMH drops while the ovarian reserve is preserved, we must distinguish between the true ovarian reserve and the functional proxy we measure in the blood.
To correctly interpret AMH panels in longevity patients, clinicians must differentiate between the absolute primordial follicle reserve and the actively developing follicle pool.
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mTORC1 and Follicle Recruitment: The mammalian target of rapamycin complex 1 (mTORC1) acts as the primary metabolic sensor triggering the activation of dormant, primordial follicles. Hyperactivation of this pathway accelerates the depletion of the ovarian reserve.
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Origin of AMH: AMH is exclusively secreted by the granulosa cells of growing preantral and small antral follicles; it is not produced by dormant primordial follicles.
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The Pharmacological Brake: A 6 mg weekly dose of rapamycin provides robust, systemic mTORC1 inhibition. This intervention forces the primordial follicle pool to remain in a state of quiescence, significantly slowing their transition into the growing phase.
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The Biomarker Result: Because the recruitment of new follicles is suspended, the total volume of active, AMH-secreting granulosa cells diminishes as older follicles naturally mature or undergo atresia. Consequently, peripheral blood draws will show a marked decline in AMH.
6 mg Pharmacodynamics vs. Current Clinical Trials
While 6 mg weekly is a standard protocol within the longevity biohacking community, clinical baselines for ovarian aging are currently anchored at a slightly lower dose.
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The VIBRANT Trial: The foremost human trial in this space, the Validating Benefits of Rapamycin for Reproductive Aging Treatment (VIBRANT) study at Columbia University, utilizes a 5 mg/week pulsatile dose for 12 weeks in perimenopausal women (aged 35–45).
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Dose-Dependent Effects: Early institutional reports from Columbia Fertility indicate that mTOR inhibition can slow the rate of follicular loss by approximately 20% (reducing the loss from roughly 50 eggs/month to 15 eggs/month). A 6 mg weekly dose will likely achieve equivalent or slightly stronger suppression of the PI3K/Akt/mTOR pathway. However, as the dose increases, the probability of complete anovulation, menstrual irregularity, and temporary infertility during the treatment window also rises.
Clinical Management and Actionable Insights
For OBGYNs managing patients utilizing off-label rapamycin for longevity or fertility preservation:
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Pre-Treatment Baselining: It is mandatory to establish true baseline AMH and Antral Follicle Count (AFC) via transvaginal ultrasound prior to initiating rapamycin therapy.
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Intra-Treatment Monitoring: AMH draws conducted while the patient is actively taking 6 mg/week are clinically useless for assessing absolute ovarian reserve. They only serve as a proxy to confirm that the drug is successfully inhibiting mTOR and suppressing follicle recruitment.
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Washout Protocols: If the patient intends to undergo ovarian stimulation for IVF, oocyte cryopreservation, or natural conception, rapamycin must be discontinued. Continuing rapamycin during pregnancy is strictly contraindicated due to its mechanism as an immunosuppressant and cellular growth inhibitor.
Knowledge Gaps and Required Data
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Rebound Kinetics: We lack robust longitudinal data to map the exact trajectory and timeframe of AMH recovery following the cessation of a 6 mg/week protocol. The required washout period to allow mTOR reactivation, follicle recruitment, and AMH normalization before administering exogenous gonadotropins is a current clinical unknown, though 1 to 3 months is a pragmatic estimate based on the drug’s roughly 60-hour half-life and the timeline of folliculogenesis.
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Therapeutic Thresholds: It remains unverified if a 6 mg dose provides superior preservation of the ovarian reserve compared to the 5 mg dose used in VIBRANT, or if the 20% higher dose simply increases off-target metabolic side effects (e.g., hyperlipidemia, transient insulin resistance, or oral ulcers) without conferring additional gonadal benefit.
Would you like an analysis of the proposed washout protocols and the theoretical optimal timing for resuming standard IVF stimulation tracking after a patient ceases a 6 mg weekly rapamycin regimen?