Reproductive hormones in infertile men with Y chromosome microdeletions

Malene Asp Bock Mejdahl; Lise Aksglaede; Anders Juul; Iben Bache; Kristian Almstrup

doi:10.1530/endoabs.110.P26

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Endocrine Abstracts (2025) 110 P26 | DOI: 10.1530/endoabs.110.P26

ECEESPE2025 Poster Presentations Reproductive and Developmental Endocrinology (93 abstracts)

Reproductive hormones in infertile men with Y chromosome microdeletions

Malene Asp Bock Mejdahl ^1,2,3 , Lise Aksglaede ^1,3 , Anders Juul ^1,3,4 , Iben Bache ² & Kristian Almstrup ^1,3,5

Author affiliations

¹Department of Growth and Reproduction, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark; ²Department of Clinical Genetics, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark; ³International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health, Copenhagen, Denmark; ⁴Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; ⁵Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark

JOINT437

Background: Microdeletions in the AZF regions of the Y chromosome are well-recognized as a recurrent genetic cause of male infertility. The reproductive system is tightly regulated by hormones of the hypothalamic–pituitary–gonadal axis but large-scale studies investigating the endocrine effects of Y microdeletions are lacking.

Objective: The objective of this study is to investigate the level of reproductive hormones in infertile men with and without Y microdeletions.

Materials and methods: Results from a PCR based Y microdeletion analysis and hormone analyses (testosterone (n=7429), free testosterone (n=7416), LH (n=7509), SHBG (n=7506), FSH (n=7488), inhibin B (n=7535), and INSL3 (n=924)) were obtained from 7615 infertile men (age 20–60) evaluated from 1997 until 2024 at the Department of Growth and Reproduction, Rigshospitalet, prior to fertility treatment.

Results: Out of 7615 analysed patients, 564 (7.4%) had a Y microdeletion and 7051 had no Y microdeletion detected. Patients were grouped based on the specific type of microdeletions: gr/gr (n=263), b1/b3 (n=3), b2/b3 (n=166), b2/b4 (n=45), AZFabc (n=16), AZFbc (n=21) and complex deletions (n=50). Inhibin B and the inhibin B/FSH ratio were significantly lower in patients with b2/b4, AZFabc, AZFbc, and complex deletions (P < 0.05) mirrored by significantly higher FSH levels in the same patients (P < 0.05). Testosterone and free testosterone concentrations were significantly lower in patients with a AZFabc deletion (P < 0.001), whereas LH was significantly higher in patients with b2/b4, AZFabc and AZFbc (P < 0.05). Reproductive hormones in patients carrying gr/gr and b2/b3 deletions did not differ significantly from patients without Y microdeletions. We did not have enough patients in the b1/b3 group or data on INSL3 to allow subdivision into specific types of microdeletions, however across all patients with Y microdeletions INSL3 did not differ significantly (P=0.71) when compared to patients without Y microdeletions.

Discussion and conclusions: Infertile men with larger and complex Y microdeletions have significantly lower inhibin B and inhibin B/FSH ratio along with significantly higher gonadotropins compared to infertile men without Y microdeletions. Only men with complete AZFabc deletions have significantly lower testosterone and free testosterone concentrations. We cannot deduce whether these differences are a direct or indirect effect of the microdeletions.