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ForumsLab Results & BiomarkersSHBG changes during weight loss on GLP-1 — hormonal implications

SHBG changes during weight loss on GLP-1 — hormonal implications

Dr.ReproEndo Tue, Mar 3, 2026 at 2:44 AM 17 replies 420 viewsPage 1 of 4
Dr.ReproEndo
Senior Member
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Jan 2024
Scottsdale, AZ
Mar 3, 2026 at 4:09 AM#1
Alright guys, I have to share this because I was not expecting it. I'm a 41-year-old male, started tirzepatide 9 months ago primarily for weight loss (SW: 278, CW: 218). My urologist had me on TRT (testosterone cypionate 100mg/week) for low T. My hormone panels are wild: | Marker | Pre-Tirz (on TRT) | 5 Mo (on TRT) | 9 Mo (OFF TRT 8 wks) | Ref Range | |--------|-------------------|---------------|---------------------|-----------| | Total T | 612 ng/dL | 824 ng/dL | 688 ng/dL | 264-916 | | Free T | 12.4 pg/mL | 18.2 pg/mL | 15.8 pg/mL | 8.7-25.1 | | SHBG | 18 nmol/L | 32 nmol/L | 38 nmol/L | 16-55 | | Estradiol | 48 pg/mL | 28 pg/mL | 22 pg/mL | 8-35 | | LH | <0.2 (suppressed on TRT) | <0.2 | 5.8 mIU/mL | 1.7-8.6 | | FSH | <0.5 (suppressed) | <0.5 | 4.2 mIU/mL | 1.5-12.4 | READ THAT AGAIN. I came OFF TRT 8 weeks ago and my total testosterone is 688 — HIGHER than it was ON TRT before weight loss. My LH and FSH recovered, meaning my hypothalamic-pituitary axis restarted. My urologist said the weight loss restored my endogenous testosterone production. He said obesity suppresses testosterone through multiple mechanisms and that dramatic fat loss can be "curative" for many cases of obesity-related hypogonadism. I haven't injected testosterone in 2 months and I feel BETTER than I did on TRT. This is life changing.
30 11mona_PHX, andrew_nyc, Dr.EndoEP and 27 others
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lori_vegas
Member
378
1,678
Aug 2024
Las Vegas, NV
Mar 3, 2026 at 4:26 AM#2
Dude. This is exactly what I needed to see. I'm 38, BMI 36, on TRT for 2 years. Total T was 248 before TRT. Always wondered if it was the weight causing the low T or if I genuinely had primary hypogonadism. How did your urologist determine it was safe to come off TRT? Did you taper or just stop?
32 22bbq_ray_KC, oliver_london, tane_welly and 29 others
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Dr.NutriCornell
Senior Member
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6,234
Mar 2024
Ithaca, NY
Mar 3, 2026 at 4:43 AM#3
He actually suggested trying because of how much weight I'd lost. We did a supervised discontinuation: - Stopped testosterone cypionate - Started enclomiphene 12.5mg for 4 weeks (to kickstart LH/FSH) - Checked labs at 4 weeks and 8 weeks - LH was already 3.2 at 4 weeks — clear sign of recovery - By 8 weeks, LH 5.8, total T 688 — we declared victory He said if my T had been below 350 at 8 weeks we would have resumed TRT. But it came roaring back. The key indicator is LH recovery — if LH comes back but T stays low, that suggests primary testicular failure. If LH recovers AND T rises, it was central/obesity-related suppression all along.
15 23laura_annarbor, JenMemphis, pat_auckland and 12 others
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jason_paloalto
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890
Nov 2024
Palo Alto, CA
Mar 3, 2026 at 5:00 AM#4
's experience is well-supported by the literature. Here's the physiology: Why obesity causes low testosterone: 1. Adipose tissue contains aromatase, which converts testosterone to estradiol → high estradiol suppresses LH via negative feedback → low T 2. Visceral fat produces inflammatory cytokines (TNF-alpha, IL-6) that directly suppress testicular Leydig cell function 3. Insulin resistance impairs SHBG production → more free T available for aromatization → vicious cycle 4. Leptin resistance in obesity disrupts GnRH pulsatility Why weight loss restores testosterone: - Less aromatase activity → less estradiol → disinhibition of LH - Improved insulin sensitivity → increased SHBG → appropriate binding - Reduced inflammation → restored Leydig cell function Studies show 15-20% body weight loss can increase total testosterone by 200-300 ng/dL in obese men. Mike lost 60 lbs (22% of body weight) — his results are right in the expected range. Important caveat: This applies to obesity-related (functional) hypogonadism. Men with true primary hypogonadism (Klinefelter's, testicular injury, etc.) will still need TRT regardless of weight loss.
Last edited: Mar 3, 2026 at 10:00 AM
43 3andrew_nyc, Dr.EndoEP, GraceAZ_72 and 40 others
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hank_denver
Member
278
1,234
Sep 2024
Denver, CO
Mar 3, 2026 at 5:17 AM#5
Can we talk about the female hormone changes too? I'm 36F, PCOS, on semaglutide 6 months. My changes are different but equally significant: | Marker | Baseline | Month 6 | Ref Range (Follicular) | |--------|----------|---------|----------------------| | Total Testosterone | 68 ng/dL | 38 ng/dL | 15-46 | | Free Testosterone | 8.2 pg/mL | 4.1 pg/mL | 0.5-4.6 | | DHEA-S | 428 µg/dL | 312 µg/dL | 65-380 | | SHBG | 22 nmol/L | 48 nmol/L | 18-114 | | Estradiol | 82 pg/mL | 54 pg/mL | 12-166 | | AMH | 8.2 ng/mL | 6.1 ng/mL | 1.0-10.0 | My testosterone normalized for the first time in years. My PCOS symptoms are dramatically better — less acne, less facial hair, and (TMI?) my periods are finally regular for the first time since I was 16. My RE says the insulin sensitization is addressing the root cause of my PCOS.
Last edited: Mar 3, 2026 at 9:17 AM
18 6Dr.DermMIA, fiona_VT, denise_HTX and 15 others
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