Tommiska J, Känsäkoski J, Pitteloud N, Wu F, Raivio T. Gonadotropin-Releasing Hormone Receptor Mutations in Aging Men. Clinical Endocrinology. http://onlinelibrary.wiley.com/doi/10.1111/cen.12833/abstract
An ongoing controversy exists on the presence of andropause in aging men. Our previous findings show that some aging men exhibit decreased circulating testosterone levels in combination with low or low-normal gonadotropin levels, a condition resembling adult-onset hypogonadotropic hypogonadism.
We recently described a patient with a homozygous p.R262Q mutation in the GNRHR gene coding for gonadotropin-releasing hormone receptor; he presented with fascinating temporal variation in his phenotype with periods of hypogonadotropic hypogonadism, reversal, and relapse at a later age.
Biallelic GNRHR mutations are the most common genetic cause of normosmic congenital hypogonadotropic hypogonadism (CHH). However, we have detected carrier frequencies of GNRHR mutations of 2.1% to 4.8% at population level in different cohorts without CHH, but, at the same time, CHH is much rarer than would be expected based on Hardy-Weinberg's law (the 2% carrier frequency would produce the incidence of 1:9800; 4% would produce 1:2400).
An ongoing controversy exists on the presence of andropause in aging men. Our previous findings show that some aging men exhibit decreased circulating testosterone levels in combination with low or low-normal gonadotropin levels, a condition resembling adult-onset hypogonadotropic hypogonadism.
We recently described a patient with a homozygous p.R262Q mutation in the GNRHR gene coding for gonadotropin-releasing hormone receptor; he presented with fascinating temporal variation in his phenotype with periods of hypogonadotropic hypogonadism, reversal, and relapse at a later age.
Biallelic GNRHR mutations are the most common genetic cause of normosmic congenital hypogonadotropic hypogonadism (CHH). However, we have detected carrier frequencies of GNRHR mutations of 2.1% to 4.8% at population level in different cohorts without CHH, but, at the same time, CHH is much rarer than would be expected based on Hardy-Weinberg's law (the 2% carrier frequency would produce the incidence of 1:9800; 4% would produce 1:2400).
