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Is thyroid hormones evaluation of clinical value in the work-up of males of infertile couples?

Authors: Lotti F, Maseroli E, Fralassi N, Degl’Innocenti S, Boni L, Baldi E, Maggi M.
DOI: 10.1093/humrep/dev338
Abstract

STUDY QUESTION:
Is thyroid hormones (TH) evaluation of clinical value in the work-up of males of infertile couples?

STUDY ANSWER:
Our results suggest that TH evaluation is not mandatory in the work-up of male infertility.

WHAT IS KNOWN ALREADY:
A few previous studies performed on a limited series of subjects reported a negative impact of hyper- and hypo-thyroidism on semen volume, sperm concentration, progressive motility and normal morphology. No previous study has systematically evaluated associations between TH variation, semen parameters and ultrasound characteristics of the male genital tract.

STUDY DESIGN, SIZE AND DURATION:
Cross-sectional analysis of a consecutive series of 172 subjects seeking medical care for couple infertility from September 2010 to November 2014.

PARTICIPANTS/MATERIALS, SETTING, METHODS:
Of the entire cohort, 163 men (age 38.9 ± 8.0 years) free of genetic abnormalities were studied. All subjects underwent a complete andrological and physical examination, biochemical and hormonal assessment, scrotal and transrectal colour-Doppler ultrasound (CDUS) and semen analysis (including seminal interleukin 8 levels, sIL-8) evaluation within the same day.

MAIN RESULTS AND THE ROLE OF CHANCE:
Among the patients studied, 145 (88.9%) showed euthyroidism, 6 (3.7%) subclinical hyper- and 12 (7.4%) subclinical hypo-thyroidism. No subjects showed overt hyper- or hypo-thyroidism. At univariate analysis, no associations among thyroid-stimulating hormone (TSH) or TH levels and sperm parameters were observed. Conversely, we observed positive associations among free triiodothyronine (fT3) and free thyroxine (fT4) levels, ejaculate volume and seminal fructose levels. In a multivariate model, after adjusting for confounders such as age, body mass index, smoking habit, sexual abstinence, calculated free testosterone, prolactin and sIL-8 levels, only the associations found for fT3 levels were confirmed. When CDUS features were investigated, using the same multivariate model, we found positive associations between fT3 levels and seminal vesicles (SV) volume, both before and after ejaculation (adj. r = 0.354 and adj. r = 0.318, both P < 0.0001), as well as with SV emptying (ΔSV volume; adj. r = 0.346, P < 0.0001) and echo-texture inhomogeneity. In addition, after adjusting for confounders, negative associations between fT4 levels and epididymal body and tail diameters were found. No significant associations between TSH or TH levels and CDUS features of other organs of the male genital tract, including testis and prostate, were found. Finally, when the features of subjects with euthyroidism, subclinical hypo- and hyper-thyroidism were compared, no significant differences in seminal or hormonal parameters were found. Conversely, evaluating CDUS parameters, subjects with subclinical hyperthyroidism showed a higher difference between the SV longitudinal diameters measured before and after ejaculation when compared with that of subclinical hypothyroid men, even after adjusting for confounders (P < 0.007). All the other male genital tract CDUS characteristics did not differ among groups.

LIMITATIONS, REASONS FOR CAUTION:
First, the number of patients investigated is relatively small and those with (subclinical) thyroid dysfunctions are an even smaller number; hence, it is therefore difficult to draw firm conclusions. Moreover, the present results are derived from patients consulting an Italian Andrology Clinic for couple infertility, and could have different characteristics from the male general population or from those males consulting general practitioners for reasons other than couple infertility. Finally, due to the cross-sectional nature of the study, neither a causality hypothesis nor mechanistic models can be inferred.

WIDER IMPLICATIONS OF THE FINDINGS:
Although no associations between TH and sperm parameters were observed, present data support a positive effect of TH on SV size and a permissive role on the ejaculatory machinery, likely through an action on SV and epididymal contractility. This is the first study reporting such evidence. However, in contrast with the view that TH assessment is important for female fertility, our results do not support a systematic evaluation of thyroid function in males of infertile couples. How TH abnormalities impact male fertility needs to be addressed by further studies.

STUDY FUNDING/COMPETING INTERESTS:
No funding was received for the study. None of the authors have any conflict of interest to declare.

© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

KEYWORDS:
ejaculate volume; fructose; infertile men; seminal vesicles ultrasound; thyroid hormones

m_dev33801

Associations between TH and significant seminal parameters. Associations between fT3 and fT4 levels and ejaculate volume (A and B, respectively) and seminal fructose levels (C and D, respectively) are reported. r and P value of the univariate analysis are reported. For each panel, a scale of circles of increasing size with a number on the right shows the number of subjects represented by each circle.

m_dev33802

Associations between fT3 or subclinical hyperthyroidism and significant SV ultrasound features. Associations between fT3 levels and SV total volume before (A) and after (B) ejaculation, and with their difference (Δ SV volume, C). r and P value of the univariate analysis are reported. For each panel, a scale of circles of increasing size with a number on the right shows the number of subjects represented by each circle. (D) The difference in reduction (Δ) of SV longitudinal diameters with ejaculation comparing subjects with euthyroidism, subclinical hypo- and hyper-thyroidism. * P< 0.01 versus other groups at Mann–Whitney analysis.

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