Authors
Nicholas Bedi, Ranjith Ramasamy
Published in
Current opinion in urology. Jul 17, 2026. Epub Jul 17, 2026.
Abstract
Elevated follicle-stimulating hormone (FSH) in primary hypogonadism is usually read as maximal but failing testicular stimulation, and affected men are often considered poor candidates for hormonal therapy. This is a hypothesis-generating narrative review rather than an evidence-based treatment recommendation. It re-examines that assumption and asks whether FSH bioactivity, rather than concentration alone, might shape the testicular response.
Circulating FSH is a mixture of glycosylation-dependent isoforms that differ in receptor-binding efficiency in experimental systems. Chronic gonadotropin excess can downregulate and desensitize the FSH receptor in animal and in vitro models. In principle, these mechanisms could combine to produce a state of functional FSH resistance, in which immunoreactive FSH is high while the effective signal in the testes is weaker. FSH suppression-associated rises in inhibin B, contemporary staged conditioning protocols, and stratification of hypergonadotropic men under the APHRODITE criteria are consistent with a strategy of temporary suppression before stimulation.
We outline the FSH reset hypothesis, in which a finite period of pituitary suppression reduces inefficient endogenous hormone and may allow receptor recovery before controlled recombinant FSH. We then present a stepwise treatment algorithm as a model for future investigation in selected men with spermatogenic failure. The hypothesis is speculative and remains unproven in prospective trials.
PMID:
42464776
Bibliographic data and abstract were imported from PubMed on 17 Jul 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 3
- Comments 0