Infertile Men Have Frequently Leydig Cell Dysfunction: Study on Hypogonadism, Vitamin D and Bone Mass in 5,177 Subjects

Presentation Number: THR-131
Date of Presentation: March 5th, 2015

Alberto Ferlin*1, Andrea Garolla2, Riccardo Selice1, Nicola Caretta2, Damiano Pizzol1 and Carlo Foresta1
1University of Padova, Padova, Italy, 2University of Padua, Padua, Italy

Abstract

Male factors are responsible for half of the cases of couple infertility. Whatever the cause, spermatogenic disruption is clinically and hormonally recognized by low sperm count and Sertoli cell markers. However, recent evidence showed that Leydig cell impairment is also frequent in subjects with primary testicular damage, as evidenced for example by reduced INSL3 and 25(OH)-vitamin D levels. The latter is caused by reduced expression of CYP2R1, a major enzyme involved in 25-hydroxylation of cholecalciferol, and lower 25(OH)-vitamin D levels are well known cause of low bone mass. Furthermore, testosterone (T) production by the Leydig cells might be also impaired in men with primary spermatogenic damage. To clarify these aspects that previous reports analyzed only separately and on limited number of subjects, in this study we evaluated the presence and type of hypogonadism, 25(OH)-vitamin D status and bone mass in a very large cohort of infertile males. Among subjects referred to our tertiary Universitary Centre for semen analysis during the period January 2011-June 2014 (11,516 semen analysis) we report here the data of men who completed the andrological program, including semen culture (n: 10,394), history and physical examination (n: 7,527), hormone analysis (FSH, LH, T, 25(OH)-vitamin D; n: 5,884), and ultrasound of the testes (n: 5,177). Men with total sperm count <10 million/ejaculate (n: 2,583) underwent also genetic analysis (karyotype, Y chromosome microdeletions, CFTR mutations; n: 2273) and DEXA (n: 855). Azoospermia was present in 9.3% of cases (n: 481/5,177), oligozoospermia (with or without reduced motility and/or normal sperm morphology) in 40.6% (n: 2302), asthenozoospermia in 12.2% (n: 632), and normozoospermia in 34.5% (n: 1787). Main causes or risk factors were varicocele (28%), genetics (15%), obstruction/sub-obstruction of seminal tract (12%), cryptorchidism (6%), infections/iatrogenic causes/ejaculation disorders/prior surgery (14%) and idiopathic forms (25%). Primary hypogonadism (T<10.4 nmol/L, LH>8 IU/L) was found in 25.7% of cases, secondary hypogonadism (T<10.4 nmol/L, LH<1.5 IU/L) in 1.3%, subclinical hypogonadism (T>10.4 nmol/L, LH>8 IU/L) in34.2%. Men with all forms of hypogonadism have frequently insufficient (48.5%) or deficient (25.4%) 25(OH)-vitamin D levels and higher risk of low bone mass, osteoporosis (16.8%) and osteopenia (31.5%). This study, performed in a very large cohort of subjects, showed that hypogonadism and low vitamin D levels are very frequent in infertile males. Both conditions, caused by Leydig cell dysfunction, are implicated in the frequent low bone mass seen in these patients. Metabolic and other clinical conditions associated with low T and low vitamin D levels need therefore to be accurately evaluated in these subjects, and treatment should consider also these aspects other than specific treatment only of infertility.

 

Nothing to Disclose: AF, AG, RS, NC, DP, CF