The adverse effects of psychotropic drugs as an endocrine disrupting chemicals on the hypothalamic-pituitary regulation in male

Abstract

Adverse effects of drugs on male reproductive system can be categorized as pre-testicular, testicular, and post-testicular. Pre-testicular adverse effects disrupt the hypothalamic–pituitary–gonadal (HPG) axis, generally by interfering with endocrine function. It is known that the HPG axis has roles in the maintenance of spermatogenesis and sexual function. The hypothalamus secretes gonadotropin-releasing hormone (GnRH) which enters the hypophyseal portal system to stimulate the anterior pituitary. The anterior pituitary secretes gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) which are vital for spermatogenesis, into the blood. The FSH stimulates the Sertoli cells for the production of regulatory molecules and nutrients needed for the maintenance of spermatogenesis, while the LH stimulates the Leydig cells to produce and secrete testosterone. Many neurotransmitters influence the hypothalamic-pituitary regulation, consequently the HPG axis, and can consequently affect spermatogenesis and sexual function. Psychotropic drugs including antipsychotics, antidepressants, and mood stabilizers that all commonly modulate dopamine, serotonin, and GABA, can affect male spermatogenesis and sexual function by impairment of the hypothalamic-pituitary regulation, act like endocrine-disrupting chemicals. Otherwise, studies have shown the relationship between decreased sperm quality and psychotropic drugs treatment. Therefore, it is important to investigate the adverse reproductive effects of psychotropic drugs which are frequently used during reproductive ages in males and to determine the role of the hypothalamic-pituitary regulation axis on possible pathologies.

Introduction

During the last decades, it has been demonstrated by studies that drugs-induced noxious and unintended responses are one of the important health problems [1,2]. Adverse drug reactions can adversely affect an individual's quality of life, often causing considerable morbidity and mortality [3,4]. It has been attention male infertility increases and sperm quality decreases in today's world [[5], [6], [7]], therefore, it is really very important to determine the adverse reproductive effects of drugs.

As known, the incidence of diseases increases with age, therefore the use of drugs increases [8], so when we get older we use more drugs. Research shows that 40% of men aged 18 to 34 use prescription drugs and over the counter (OTC) drugs, while this rate increases to 50% in men aged 35 to 49 and up to 70% in men aged 50 to 64 [9]. Although it is known that fertility decreases with age, men can be fertile up to 60; which means that a significant portion of drug exposures occur in men at reproductive ages. But, during any drug treatment, reproductive plans of men are not questioned. Because the awareness that drugs can cause adverse reproductive effects and reduce fertility potential in men is not enough. In fact, for drugs that were introduced to the market before 2011, it was not even mandatory to assess the reproductive toxicity in men. However, in 2011, reproductive toxicity testing in men have been a part of pre-marketing studies [[10], [11], [12], [13]]. But, when it has been considered that most of the drugs used in treatment today have been introduced before 2011, it becomes that insufficient knowledge about the adverse reproductive effects induced with drugs in men.