Andrew A Dwyer1,2, Niraj R Chavan3, Hilana Lewkowitz-Shpuntoff2,4, Lacey Plummer2, Frances J Hayes2, Stephanie B Seminara2, William F Crowley2, Nelly Pitteloud5, Ravikumar Balasubramanian2. 1. Boston College William F. Connell School of Nursing, Chestnut Hill, Massachusetts. 2. Harvard Reproductive Endocrine Sciences Center and Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. 3. Department of Obstetrics and Gynecology, University of Kentucky College of Medicine, Lexington, Kentucky. 4. Department of Anesthesiology, Columbia University Medical Center, New York, New York. 5. Endocrinology, Diabetes, and Metabolism Service, University Hospital of Lausanne, Lausanne, Switzerland.
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.
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.
Authors: Joseph A Alemany; Bradley C Nindl; Mark D Kellogg; William J Tharion; Andrew J Young; Scott J Montain Journal: J Appl Physiol (1985) Date: 2008-05-01
Authors: Andrew A Dwyer; Gerasimos P Sykiotis; Frances J Hayes; Paul A Boepple; Hang Lee; Kevin R Loughlin; Martin Dym; Patrick M Sluss; William F Crowley; Nelly Pitteloud Journal: J Clin Endocrinol Metab Date: 2013-09-13 Impact factor: 5.958