Metabolic syndrome in white European men presenting for primary couple's infertility: investigation of the clinical and reproductive burden

Abstract

SUMMARYDespite complex interactions between obesity, dyslipidemia, hyperinsulinaemia, and the reproductive axis, the impact of metabolic syndrome on human male reproductive function has not been analysed comprehensively. Complete demographic, clinical, and laboratory data from 1337 consecutive primary infertile men were analysed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (categorised 0 vs. 1 vs. 2 or higher). NCEP-ATPIII criteria were used to define metabolic syndrome. Semen analysis values were assessed based on the 2010 World Health Organisation (WHO) reference criteria. Descriptive statistics and logistic regression models tested the association between semen parameters and clinical characteristics and metabolic syndrome. Metabolic syndrome was found in 128 (9.6%) of 1337 men. Patients with metabolic syndrome were older (p < 0.001) and had a greater Charlson Comorbidity Index of 1 or higher (chi-square: 15.6; p < 0.001) compared with those without metabolic syndrome. Metabolic syndrome patients had lower levels of total testosterone (p < 0.001), sex hormone-binding globulin (p = 0.004), inhibin B (p = 0.03), and anti-M€ ullerian hormone (p = 0.009), and they were hypogonadal at a higher rate (chi-square: 32.0; p < 0.001) than patients without metabolic syndrome. Conversely, the two groups did not differ significantly in further hormonal levels, semen parameters, and rate of either obstructive or non-obstructive azoospermia. At multivariate logistic regression analysis, testicular volume (OR: 0.90; p = 0.002) achieved independent predictor status for WHO pathological semen concentration; conversely, age, Charlson Comorbidity Index scores, metabolic syndrome, and inhibin B values did not. No parameters predicted normal sperm morphology and total progressive motility. Metabolic syndrome accounts for roughly 9% of men presenting for primary couple's infertility. Although metabolic syndrome patients have a lower general male health status, semen analysis values seem independent of the presence of metabolic syndrome.

Effect of clomiphene citrate treatment on the Sertoli cells of dysmetabolic obese men with low testosterone levels

“…These results strengthen previously compelling evidence indicating that obesity, metabolic syndrome and type 2 diabetes mellitus cause a severe damage to SC, irrespective of the fertility condition and of the age of the male . Furthermore, the testes impairment has been associated with the individual components of metabolic syndrome …”

“…Our in‐house reference range obtained from a different population of 40 adult fertile nonobese men aged 24‐40 years was 35‐305 pg/mL or ng/L. These values are in line with other studies that used the same kit . As reported in our previous study, serum steroid hormones were measured by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) using reference intervals in healthy adult men by Fanelli et al Gonadotropins and sex hormone‐binding globulin (SHBG) were measured at the Central Laboratory of S.Orsola Malpighi Hospital (Bologna, Italy) by Modular Analytics E 170 (Roche Diagnostics) and by Immulite 2000 (Siemens Healthcare Diagnostics), respectively, as previously described …”

“…However, to date, there is the unequivocal evidence regarding SC function in men with dysmetabolic conditions. [11][12][13] Recently, we performed a randomized controlled study (RCT) on obese DHH patients with low T showing that CC at low doses (25 mg/day) significantly increased LH secretion and in turn, elicited T response from LCs, reinforcing the theory that these are reversible forms of hypogonadism. 9 We therefore decided to analyse the functional state of SC by measuring the serum levels of Inhibin (IB) and anti-Mullerian hormone (AMH) in 10 subjects from the same population and treatment strategy.…”

“…Interestingly, circulating IB and AMH levels have been described to be lower in patients with metabolic disturbances than in infertile men without metabolic syndrome or/and prediabetes. This suggests the negative impact of dysmetabolic conditions on SC function, besides the well‐known effect on LC …”

Epidemiological and Clinical Profile in an Azoospermic Male-A Tertiary Care Experience

“…Majority of them were diabetic followed by systemic hypertension. 8 Another important point to note was history of mumps orchitis in the childhood (11%) which is a vaccine preventable disease. Thirty two percent had an identifiable testicular problem.…”