The enclomiphene piece is doing a lot of work in these threads, and most of them skip the step that actually explains why SHBG stays elevated. Enclomiphene is a SERM, a selective estrogen receptor modulator. It blocks estrogen feedback at the hypothalamus, which releases the brake on LH and FSH (luteinizing and follicle-stimulating hormone), which signals the testes to produce more T. More T means more substrate for aromatase. E2 goes up. And hepatic SHBG (sex hormone-binding globulin) production is partly driven by estrogen signaling at the liver. So if SHBG is still >100 after six months on enclomiphene, the first thing I’d want to see isn’t a dose adjustment, it’s your E2. Sensitive LC-MS/MS assay specifically, not the standard immunoassay, which routinely underreports at higher estradiol ranges. Labs worth pulling at next draw:
- Total T and calculated free T (albumin + SHBG method, not direct immunoassay)
- E2, sensitive assay
- LH, FSH
- Albumin
- TSH if not recent, thyroid drives SHBG independently of sex hormones The number that matters isn’t SHBG in isolation. SHBG at 108 with free T in range is a different clinical picture than SHBG at 108 with free T floored. HPG (hypothalamic-pituitary-gonadal) axis recovery at 18 can be slower than people expect even with SERM support. Six months with labs trending in any direction isn’t a ceiling, it’s a data point.