Reproductive Phenotypes and Genotypes in Men With Isolated Hypogonadotropic Hypogonadism (IHH)
Main finding · Partial puberty as predictor of pulsatile LH secretionResult — go to the resultOdds ratio 10.8 95% CI 3.6–38.6Authors' conclusion
Partial puberty and LH greater than or equal to 2.10 IU/L are proxies for pulsatile LH secretion. ANOS1 PTVs confer severe reproductive phenotypes. Variable phenotypic severity in the face of severe genetic variants in other IHH genes point to significant neuroendocrine plasticity of the HPG axis in IHH men.
Study context
- Population
- Men with isolated hypogonadotropic hypogonadism (IHH), 1980–2020204 with exome sequencing (ES) data
- Participants
- 242 men
- Exposure
- Genotypic severity vs pubertal and neuroendocrine phenotypes
- KSn = 131
- nHHn = 111
- Outcome
- Correlation between genotypic severity and pubertal and neuroendocrine phenotypes
Main finding
As reported in the abstract
Partial puberty as predictor of pulsatile LH secretion
Odds ratio
10.8
95% CI 3.6–38.6
P < 0.001
Partial pubertyvs Absent puberty
OR 10.8 (95% CI 3.6–38.6); P < 0.001
- Absent puberty: significantly lower gonadotropin levels
- P < 0.001
- Absent puberty: more likely undetectable LH
- P < 0.001
- Serum LH 2.10 IU/L: true positive rate for predicting LH pulsatility
- 95%
Observational data: associations, not effects.
Further findings
Protein-truncating variants (PTVs) in 12 IHH genes
- Men carrying PTVs
- 36 of 204 (18%)
- Absent puberty and apulsatile LH enriched for oligogenic PTVs, ANOS1 predominant
- P < 0.001
- Absent puberty enriched for ANOS1 PTVs vs partial puberty
- P = 0.002
- PTVs in other IHH genes imparted more variable reproductive phenotypic severity
Original publication
Reproductive Phenotypes and Genotypes in Men With IHH. J Clin Endocrinol Metab. Published 21 October 2022. doi:10.
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