Author: Elmoataz Elmamoun PharmD Candidate, 2022, South College School of Pharmacy
Insulin-dependent diabetes mellitus, i.e. type 1 diabetes, may be linked to male reproductive dysfunction and fertility issues.
The World Health Organization (WHO) defines infertility as a disease of the male or female reproductive system characterized by failing to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse, affecting an estimated 10% of reproductive-aged couples globally. At the same time, secondary infertility is linked to the causes of most female infertility worldwide and is often caused by reproductive tract infection. Male infertility accounts for 20-30% of all cases but contributes to 50% of all cases and is often attributed to sperm formation deficiencies, concentration, or transportation. Several etiologies are responsible for male infertility and are classified based on their general underlying cause, including endocrine disorders, primary testicular defects, congenital urogenital abnormalities, and idiopathic. Diagnosis of male infertility is based primarily on semen analysis and includes assessing semen volume, quality, density, total motility, morphology, and signs of infection.
Diabetes mellitus (DM) has been implicated in many systemic complications and is a significant cause of long-term morbidity, organ dysfunction, and failures, including disturbance in the male reproductive system, leading to various complications such as impotence and retrograde ejaculation, and hypogonadism. These complications can be seen in either type 1 or type 2 diabetes mellitus. In addition, they can have unfavorable effects on male fertility, especially on sperm motility, sperm DNA integrity, and ingredients of seminal plasma, although the exact mechanism by which DM may affect male fertility has not been fully elucidated. Yet, despite the favorable effect of insulin on gonadal function and spermatogenesis, research has shown that the sperm plasma membrane and acrosome are affected by serum insulin levels. In addition, insulin resistance or insulin deficiency may affect seminal levels of reactive oxygen species (ROS) and the processes that ensue during pre-testicular, testicular, and post-testicular, all of which can lead to alterations, spermatogenesis.
A recent systemic review meta-analyzed data on male fertility testis functions in patients with diabetes mellitus type 1 (DM1) from eight studies out of a total of 14 prospective and retrospective studies that evaluated paternity rate (rate of children by natural fertility), hormonal (male hypothalamic-pituitary-gonadal axis-HPG axis) and seminal quality in men with DM1. Several semen parameters (semen volume and pH, sperm concentration, total sperm count, sperm motility, and morphology) men with DM1 were used as primary outcomes, with men without DM1 as controls. Cochrane criteria were used to assess the quality of the trials, including design limitations, the potential for selection bias and confounding, and the potential to report biases.
The study noted that the rate of children was significantly lower in men (51.1%) and women (35.7%), p < 0.0001, with DM1, compared to the general population, with a fertility rate of 0.65 among men. Additionally, a cohort of men and women with childhood-onset of DM1 showed that they were less likely to have a first child compared to controls. This rate of having a first child was statistically significantly higher among men diagnosed with later onset of diabetes (p = 0.04). Data on the male gonadal hormonal profile of patients with DM1 were few, heterogeneous, and therefore not conclusive. However, meta analysis of seminal parameters in men with DM1 compared to controls reported that the men with DM1 have significantly lower normal sperm morphology (-0.36% (-0.66, -0.06) y, sperm progressive motility (-33.62% (-0.39.13, -28.11), and low seminal volume (-0.51(-1.03, -0.02). The analysis concluded that only a few studies had performed a comprehensive and well-defined assessment of male fertility in men with DM1. Furthermore, this review and meta-analysis suggest that DM1 can alter reproductive health to varying degrees, including alterations in sperm function and decreased fertility rates in this population. Further studies are needed to study the effects of DM1 on male fertility compared with healthy controls.
- Although the exact mechanism by which DM may affect male fertility has not been fully understood, insulin resistance or insulin deficiency may affect seminal levels of reactive oxygen species (ROS).
- Diabetes mellitus type 1 may affect male fertility and testicular functions, including spermatogenesis.
- Further studies are needed to study the effect of DM1 on male fertility.
World Health Organization (WHO). International Classification of Diseases, 11th Revision (ICD-11) Geneva: WHO 20
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Ding, Guo-Lian et al. “The effects of diabetes on male fertility and epigenetic regulation during spermatogenesis.” Asian journal of andrology vol. 17,6 (2015): 948-53. doi:10.4103/1008-682X.150844
Elmoataz Elmamoun PharmD Candidate, 2022, South College School of Pharmacy