291 ‒ Role of testosterone in men & women, performance-enhancing drugs, sustainable fat loss, & more

KEYPOINTS

• 01

  Testosterone therapy for women is often dosed far too high.

  Derek, the fitness and hormone commentator behind More Plates More Dates, and Peter discuss practitioners promoting cookie-cutter targets of 200–300 ng/dL total testosterone for women—levels in the male range. One woman, through a compounding error, took 10 times her dose for a month, effectively a male physiologic dose. Peter has never seen a woman in her 30s naturally in that range.

• 02

  Restore a woman's own physiology, not a population number.

  Premenopausal women typically run perhaps 10–20+ ng/dL (units confuse the issue—some labs report picograms). Peter might target 80–100 ng/dL, roughly 70th–80th percentile, but notes that for a woman who naturally lived lower, even 80 may be supraphysiologic—nobody measured her at 30.

• 03

  DHEA can raise testosterone in women on oral contraceptives.

  Women's androgens derive substantially from adrenal production; Derek cites papers where DHEA supplementation (25–50 mg daily) roughly quadrupled total testosterone (about 15 to 60 ng/dL) in women on the pill, which suppresses ovarian output. Even castrated men can make 30–40 ng/dL from their adrenals.

• 04

  Progesterone dosing should be individualized.

  Many women can't tolerate a full 200 mg progesterone dose but feel great at 50–100 mg; the goal is finding each woman's dose while protecting the uterus from unopposed estrogen.

• 05

  Assay choice changes your numbers dramatically.

  On the same blood, an immunoassay read testosterone 502 while LC-MS/MS read 381; estradiol was 41.3 by immunoassay versus 18.3 by LC-MS—more than double. Look for 'LC-MS/MS' on the report. Timing matters too: measuring three days after a TRT injection misses the peak and trough.

• 06

  For low-normal testosterone, address basics before TRT.

  For a symptomatic man around 300–381 ng/dL, sleep, body fat, vitamin D and other factors can move levels 100+ ng/dL. Clomiphene and hCG can raise endogenous production—hCG might take 381 to around 1,200—and Derek expects much more clomiphene use, though bodybuilders' post-cycle regimens of 100 mg/day are absurdly high.

• 07

  FDA's Category 2 peptide list restricted compounding of popular peptides.

  About 30 peptides, including BPC-157 and CJC-1295, were placed on a list the FDA said lacked sufficient safety data for compounding. Derek thinks some never should have been sold but is sad about others; he wants real trials, such as 8–12 weeks of BPC-157 in post-operative orthopedic patients.

• 08

  Myostatin inhibition is promising but expensive and modest.

  A company claims follistatin gene therapy at about $25,000 per shot. In aged mice, near-complete myostatin knockdown (over 99% of mRNA) increased muscle mass about 25%. Phase 2 sarcopenia trials could matter if people over 60 gain 5–10 pounds of muscle.

• 09

  Bodybuilding prep shows how far careful dieting can go—and its hormonal cost.

  Derek recommends starting with about a 300-calorie deficit and 'milking' it, with a split like 40% protein, 40% carbs, 20% fat. A natural sub-200 lb competitor may be below 2,000 calories on stage; a 260 lb pro might eat 2,500–2,600. Crash dieting from 2,800 to near nothing backfires.

• 10

  Extended fasting crushes hormones.

  Peter describes how 7–10 days of water fasting dropped his testosterone from 500–600 to 100–200 ng/dL, TSH from 2 to 4–6, free T3 from about 3 to 1.5, and reverse T3 from 12 to 32.

• 11

  Supraphysiologic testosterone builds muscle even without training.

  In Bhasin's classic studies, 600 mg/week (about 6x physiologic) produced the most lean mass with training—but the untrained testosterone group gained more lean mass than the training placebo group.

• 12

  Androgens like DHT shape development, so exposure timing matters.

  Derek notes DHT is best known for hair loss but is central to how masculine a person becomes during development, with critical windows of exposure. Even adult women exposing themselves to androgens can push their physiology in a masculine direction—one reason supraphysiologic dosing in women can cause irreversible changes such as voice deepening.