Variable dosing of rapamycin across the menstrual cycle phases

Hello, wonderful rapa group!
I’m a female, 44, and I took my first Rapamune dose (1mg) several days ago. Planning to try to work up to 3 or 4mg and take it once a week or so, but I was wondering what’s the best way to time and dose rapa across my cycle.
Anyone with theories, experiences or ideas, please comment!

  1. Can taking it in the luteal phase cause an early period? I read that rapamycin decreases progesterone, which should be high in that phase. My progesterone is rather low to start with (based on my Inito monitor graph). Should Rapa be taken at a lower dose in those luteal weeks, or maybe avoided altogether?

  2. Is it more likely to cause canker sores during the luteal phase? I ask because I used to often get canker sores in the week before my period, probably because of not enough lysine in the diet.

  3. My guess is mTOR is lower during mensuration itself (maybe?) so maybe rapa can be taken at higher doses then? Could it cause heavier bleeding?

4)What about the dose around ovulation? And better before or after?

  1. For women taking rapa - has it shortened or lengthened your cycles? What else should I know about best times and doses to take it throughout the cycle and things to expect?

Many thanks!

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More on the topic

Low-Dose Oral Sirolimus and the Risk of Menstrual-Cycle Disturbances and Ovarian Cysts: Analysis of the Randomized Controlled SUISSE ADPKD Trial

Adult females with autosomal dominant polycystic kidney disease, an inherited kidney disease not known to affect ovarian morphology and function, were treated with 1.3 to 1.5 mg sirolimus per day for a median of 19 months (N = 21) or standard care (N = 18). Sirolimus increased the risk of both oligoamenorrhea (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.1 to 29) and ovarian cysts (HR 4.4, CI 1.1 to 26); one patient was cystectomized five months after starting treatment with sirolimus. We also studied mechanisms of sirolimus-associated ovarian toxicity in rats. Sirolimus amplified signaling in rat ovarian follicles through the pro-proliferative phosphatidylinositol 3-kinase pathway. Low dose oral sirolimus increases the risk of menstrual cycle disturbances and ovarian cysts and monitoring of sirolimus-associated ovarian toxicity is warranted and might guide clinical practice with mammalian target of rapamycin inhibitors.

Our findings of sirolimus associated ovarian toxicity are supported by two reports of a higher frequency of oligoamenorrhea and ovarian cysts in pancreatic islet recipients treated with a dual therapy of sirolimus and tacrolimus [6], [7]. Cure and colleagues reported a higher frequency of oligoamenorrhea after transplantation and the occurrence of ovarian cysts in 8 of 13 patients, while serum follicle and luteinizing hormone levels remained in the normal range [6]. Alfadhli and colleagues reported on the occurrence of ovarian cysts in 31 of 44 premenopausal patients 8 months after transplantation and then after sirolimus withdrawal, a cyst size reduction in 80% of these 31 patients [7].

Sirolimus causes insulin resistance in rodents [19] and in humans [44], [45] and we observed cycle disturbance and ovarian cysts in our ADPKD patients when treated with sirolimus, suggesting sirolimus promotes a polycystic ovary like syndrome. In our animal study, sirolimus activated Akt in ovaries. Polymorphisms of the Akt gene were associated with an increased risk for the occurrence of PCOS in epidemiological studies [46] and an increase in the insulin-induced IRS/PI 3-kinase/Akt pathway in rat ovaries caused a PCOS like phenotype [47], suggesting this pathway has a role in the development of ovarian cysts.