Prediabetes may pose threat to male fertility

Prediabetes among men might be related to infertility, a new study suggested.

In a cohort of 744 men with primary infertility, around 15% fit the criteria for having undiagnosed prediabetes, reported Andrea Salonia, MD, PhD, of the University Vita-Salute San Raffaele in Milan, Italy, and colleagues.

"We decided to conduct this study because while previous reports have shown that diabetes mellitus is associated with impaired semen parameters, nuclear DNA fragmentation rates, and chromatin quality, very little is known about the same association with prediabetes," the study's first author, Luca Boeri, MD, of the University of Milan, told MedPage Today.

"Moreover prediabetes is a common and underdiagnosed clinical condition that can be considered a red flag for further metabolic and cardiovascular diseases. Infertility per se is nowadays considered as a proxy of the overall male health,," he said.

Writing in BJU International, the researchers reported elevated median hormonal markers among infertile men, including follicle-stimulating hormone (FSH) and 17β-estradiol (E₂), compared with infertile men without prediabetes (interquartile ranges in parentheses):

• FSH: 6.2 mUI/mL (3.9-20.0) [prediabetes] versus 4.9 mUI/mL (2.9-9.1; P<0.001)
• E₂: 30.0 pg/mL (24-41.5) vs 25.0 pg/mL (24-34; P=0.03)

In addition, medians for several other hormonal markers were significantly lower among infertile men with prediabetes compared with infertile men who had normal glucose levels (interquartile ranges in parentheses)

• Total testosterone: 3.7 ng/mL (2.9-5.3) [prediabetes] versus 4.5 ng/mL (3.4-5.7; P<0.01)
• Sex hormone-binding globulin: 30.7 nmol/L (24.7-40) versus 33.1 nmol/L (25.1-43.8; P=0.035)
• Inhibin B: 73.9 pg/mL (16.9-140.5) versus 116.8 pg/mL (60.5-167.3; P=0.001)

Despite similar sperm concentrations and semen volumes between the two groups, significantly more men with prediabetes also had sperm DNA fragmentation over the threshold of 30% (58.4% prediabetes versus 41.8%, P=0.005), the researchers reported.

For the analysis, they used the American Diabetes Association's criteria for prediabetes, defined as a fasting plasma glucose level of 100-125 mg/dL, a 2-hour, 75 g oral glucose tolerance test of 140-199 mg/dL, or an HbA1c of 5.7-6.4%.

Boeri said that although this was the first study to look at the link between prediabetes and male infertility, the findings were not especially surprising -- mainly due to the known relationship between hyperinsulinemia and androgen deficiency.

"Interestingly enough, we also found that semen parameters -- in terms of volume, count, motility and morphology -- did not differ according to the glycemic status," he explained, adding that "speculatively, we could hypothesize that these counterintuitive findings could be explained through the various evidences that testes develop glucose adaptive metabolic mechanisms to ensure an adequate microenvironment for germ cells development."

Boeri said that he recommends that clinicians assess glucose levels in male patients with infertility problems and recognize the clinical importance of prediabetes. By identifying prediabetes early, this will allow "the possible countermeasures to be taken as early as possible in relatively young persons," he said.

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