Serum Insulin-like Factor 3, Testosterone, and LH in Experimental and Therapeutic Testicular Suppression.
Albrethsen. Jakob J; Østergren. Peter Busch PB; Norup. Pernille Badsberg PB; Sønksen. Jens J; Fode. Mikkel M; Kistorp. Caroline C; Nordsborg. Nikolai B NB; Solheim. Sara Amalie SA; Mørkeberg. Jakob J; Main. Katharina M KM; Juul. Anders A
Key Findings
- INSL3 levels fall during experimental and therapeutic testicular suppression, matching the drop in testosterone and LH.
- INSL3 levels return to baseline after the suppression is lifted in healthy men.
- INSL3 can serve as a sensitive marker of Leydig cell activity, complementing testosterone measurements in monitoring hormone interventions.
Practical Outcomes
- For biohackers using testosterone or GnRH agonists, tracking INSL3 could give a clearer picture of testicular health and help detect incomplete suppression or illicit androgen use. However, INSL3 testing isn’t widely available, so accessing it may require specialized labs. Incorporating INSL3 checks could improve monitoring of hormone protocols when feasible.
Summary
The study shows that the hormone INSL3, which comes from testicular Leydig cells, drops in the same way as testosterone and LH when the testes are chemically or surgically suppressed, and it rises back when suppression stops. This means INSL3 can be used as another indicator of how the testes are functioning during hormone therapies or testosterone use.
Abstract
Serum insulin-like factor 3 (INSL3) is a Leydig cell biomarker, but little is known about the circulating concentration of INSL3 during hypothalamus-pituitary-testicular suppression. To study the concomitant changes in serum concentrations of INSL3, testosterone, and LH during experimental and therapeutic testicular suppression. We included serum samples from 3 different cohorts comprising subjects before and after testicular suppression: (1) 6 healthy young men who were treated with androgens (Sustanon, Aspen Pharma, Dublin, Ireland); 2) 10 transgender girls (male sex assigned at birth) who were treated with 3-monthly GnRH agonist injections (Leuprorelinacetat, Abacus Medicine, Copenhagen, Denmark); and (3) 55 patients with prostate cancer who were randomized to surgical castration (bilateral subcapsular orchiectomy) or treatment with GnRH agonist (Triptorelin, Ipsen Pharma, Kista, Sweden). Serum INSL3 and testosterone concentrations were quantified in stored serum samples using validated liquid chromatography-tandem mass spectrometry methodologies, and LH was measured by an ultrasensitive immunoassay. The circulating concentrations of INSL3, testosterone, and LH decreased during experimental testicular suppression in healthy young men by Sustanon injections and subsequently returned to baseline levels after release of suppression. All 3 hormones decreased during therapeutic hormonal hypothalamus-pituitary-testicular suppression in transgender girls and in patients with prostate cancer. INSL3 resembles testosterone as a sensitive marker of testicular suppression and reflects Leydig cell function, also during exposure to exogenous testosterone. Serum INSL3 measurements may complement testosterone as a Leydig cell marker in male reproductive disorders, during therapeutic testicular suppression as well as in surveillance of illicit use of androgens.
Study Information
pubmed
2023
2023-10-18T00:00:00.000Z
10.1210/clinem/dgad291
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