Functional Hypogonadotropic Hypogonadism in Men: Underlying Neuroendocrine Mechanisms and Natural History

Overview

Journal J Clin Endocrinol Metab

Publisher Oxford University Press

Specialty Endocrinology

Date 2019 Jun 21

PMID 31220265

Citations 11

Authors

Andrew A Dwyer

Niraj R Chavan

Hilana Lewkowitz-Shpuntoff

Lacey Plummer

Frances J Hayes

Stephanie B Seminara

William F Crowley

Nelly Pitteloud

Ravikumar Balasubramanian

Affiliations

Soon will be listed here.

Abstract

Context: After completion of puberty a subset of men experience functional hypogonadotropic hypogonadism (FHH) secondary to excessive exercise or weight loss. This phenomenon is akin to hypothalamic amenorrhea (HA) in women, yet little is known about FHH in men.

Objective: To investigate the neuroendocrine mechanisms, genetics, and natural history underlying FHH.

Design: Retrospective study in an academic medical center.

Participants: Healthy postpubertal men presenting with symptoms of hypogonadism in the setting of excessive exercise (>10 hours/week) or weight loss (>10% of body weight). Healthy age-matched men served as controls.

Interventions: Clinical assessment, biochemical and neuroendocrine profiling, body composition, semen analysis, and genetic evaluation of genes known to cause isolated GnRH deficiency.

Main Outcome Measures: Reproductive hormone levels, endogenous GnRH-induced LH pulse patterns, and rare genetic variants.

Results: Ten men with FHH were compared with 18 age-matched controls. Patients had significantly lower body mass index, testosterone, LH, and mean LH pulse amplitudes yet normal LH pulse frequency, serum FSH, and sperm counts. Some patients exhibited nocturnal, sleep-entrained LH pulses characteristic of early puberty, and one FHH subject showed a completely apulsatile LH secretion. After decreased exercise and weight gain, five men with men had normalized serum testosterone levels, and symptoms resolved. Rare missense variants in NSMF (n = 1) and CHD7 (n = 1) were identified in two men with FHH.

Conclusions: FHH is a rare, reversible form of male GnRH deficiency. LH pulse patterns in male FHH are similar to those observed in women with HA. This study expands the spectrum of GnRH deficiency disorders in men.

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