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ForumsLab Results & BiomarkersSHBG changes during weight loss on GLP-1 — July 2024

SHBG changes during weight loss on GLP-1 — July 2024

NicoleRaleigh Mon, Dec 8, 2025 at 6:29 PM 10 replies 790 viewsPage 1 of 2
NicoleRaleigh
Member
356
1,567
Aug 2024
Raleigh, NC
Dec 8, 2025 at 7:54 PM#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.
28 13InsuranceTom, WendyG_ATL, SaraMom3 and 25 others
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DanielChem_CHI
Senior Member
1,234
5,678
Mar 2024
Chicago, IL
Dec 8, 2025 at 8:11 PM#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?
22 19Dr.DermMIA, fiona_VT, denise_HTX and 19 others
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JennaRN
Senior Member
1,987
8,923
Mar 2024
Colorado
Online
Dec 8, 2025 at 8:28 PM#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.
34 16BiostatsBrad, PeptideSynthNJ, Dr.KarenChen and 31 others
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JenMemphis
Member
267
1,234
Jan 2025
Memphis, TN
Dec 8, 2025 at 8:45 PM#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.
7 13wanda_boise, NurseAsh_DET, BenResearch_OR and 4 others
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rachel_ABQ
Member
178
890
Dec 2024
Albuquerque, NM
Dec 8, 2025 at 9:02 PM#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: Dec 9, 2025 at 2:02 AM
24 3Dr.CardioMD, EndoResFellow, PharmacoVig_BOS and 21 others
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