hCG therapy in hypogonadic severe-oligozoospermic men and its effect on semen parameters

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Objective: This study aimed to evaluate whether human chorionic gonadotropin (hCG) therapy is beneficial for improving semen parameters and clinical hypogonadism symptoms in hypogonadic oligozoospermic or severe oligozoospermic men with low or borderline testosterone levels.

Methods: A weekly dose of 250 μg (equivalent to approximately 6,500 IU) of hCG was administered subcutaneously for 3–6 months to 56 hypogonadic oligozoospermic or severe oligozoospermic men. Semen, biochemical, and genetic analyses were performed before the start of treatment followed by analyzing semen parameters every 3 months after the start of therapy. We grouped participants into responders and non-responders depending on positive changes in semen parameters.

Results: Out of 56 men, 47 (83.93%) responded, while 9 (16.07%) did not. Upon statistical analysis, it was found that age did not affect the overall outcomes (p=0.292); however, men with higher body mass index (BMI; 28.09±3.48 kg/m2 ) showed better outcomes than those with low BMI (25.33±3.06 kg/m2 ) (p=0.042). The duration of therapy (in months) was higher in non-responders than in responders (p=0.020). We found significant improvements in sperm concentration (p=0.006) and count (p=0.005) after 3 months of therapy. Sperm motility and progressive motility were also found to be higher in responders but did not show statistically significant changes.

Conclusion: We conclude that hCG therapy can be beneficial in men with hypogonadic oligozoospermia or severe oligozoospermia.




Introduction

Male and female factors contribute equally to about 15% of couples with fertility issues [1]. Men with hypogonadism have diminished levels of testosterone, and hypogonadism coupled with reduced gonadotropin levels (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) is known as hypogonadic hypogonadism (HH). HH can either be congenital or acquired. The classical example of congenital hypogonadism is Kallmann syndrome, while acquired hypogonadism can occur due to pituitary lesions causing hyperprolactinemia or as a result of anabolic steroid usage. During spermatogenesis, which is regulated by hormones, the differentiation of stem cells starts in the testes. Gonadotropin-releasing hormone (GnRH) from the hypothalamus is released in a pulsatile manner to stimulate the production of FSH and LH in the anterior lobe of the pituitary gland [2]. FSH helps in spermatogenesis by directly stimulating Sertoli cells, while LH stimulates testosterone production from Leydig cells. Testicular testosterone regulates spermatogenesis by its action on Sertoli cells, while peripheral testosterone plays an important role in sexual function in men in the form of libido, erectile function, and ejaculation [3]. For successful spermatogenesis, the functioning of the hypothalamus-pituitary-gonadal axis is critical and any alterations in this axis can give rise to hypogonadism, which can result in spermatogenic failure and affect male fertility [4].

Generally, testosterone levels start declining after around 40 years, and by 80 years, they are reduced by almost half [5]. Hypogonadism is characterized by low serum testosterone levels coupled with low libido, erectile dysfunction, low energy, depression, anemia, infertility, and many more clinical symptoms [6-8]. Hypogonadism affects 38% of men over 45 years of age and 7% of men under 40 years of age [9,10]. Although the clinical symptoms of hypogonadism are primarily signs of aging in men [6], early-onset hypogonadism may also affect fertility in men of reproductive age. In the past few decades, its prevalence in younger generations has increased exponentially, probably due to the use of anabolic-androgenic steroids [9]. Human chorionic gonadotropin (hCG), an analog of LH that has a longer half-life (36 hours), plays an important role in the treatment of endocrine testicular failures and stimulates testosterone production by acting on Leydig cells [9]. In this study, hCG was administered to 56 hypogonadic infertile men with oligozoospermia with the goal of improving their semen profile.





2. Hormonal therapy

Based on the testosterone levels (low or borderline) and clinical symptoms, a diagnosis of adult-onset hypogonadism (AOH) was made. After diagnosing, the male partners were suggested to receive hCG therapy at a weekly dose of 250 μg. During the treatment, semen analysis was performed after every 4 weeks. No sperm was found in the ejaculate samples even after centrifugation for the first 2 months in any participants. However, after the third month, occasional sperm were found in the ejaculate in two men and at the end of 4 months, six other men responded by showing occasional sperm. All the responders agreed to continue the therapy until 6 months and three men showed normal semen parameters in the ejaculate, while three men showed oligozoospermic parameters. As advised, the couples had regular sexual intercourse.




*Our data suggest that hCG therapy is safe and effective as an alternative to exogenous testosterone therapy. In a direct evaluation of the effects of hCG on semen parameters, our results showed significant improvements in semen concentration and count. The only challenge patients face is financial, as hCG therapy is costly; however, most of the time, the desire to achieve parenthood overcomes this barrier. In men with low or borderline testosterone levels, hCG therapy should be discussed as an option to retain fertility.
 

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madman

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Table 1. Comparison of clinical characteristics between responders and non-responders
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