title: Is thyroid hormones evaluation of clinical value in the work-up of males of infertile couples?
abstract: OBJECTIVE
  Is thyroid hormones (TH) evaluation of clinical value in the work-up of males of infertile couples?
  
  
  CONCLUSIONS
  Our results suggest that TH evaluation is not mandatory in the work-up of male infertility.
  
  
  BACKGROUND
  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.
  
  
  METHODS
  Cross-sectional analysis of a consecutive series of 172 subjects seeking medical care for couple infertility from September 2010 to November 2014.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  No funding was received for the study. None of the authors have any conflict of interest to declare.
authors.affiliation: Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Lotti
authors.affiliation: Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Maseroli
authors.affiliation: Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Fralassi
authors.affiliation: Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Degl'Innocenti
authors.affiliation: Department of Oncology, Istituto Toscano Tumori/AOU Careggi, Florence, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Boni
authors.affiliation: Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Baldi
authors.affiliation: Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy m.maggi@dfc.unifi.it.
authors.forename: M
authors.initials: M
authors.lastname: Maggi
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005632:Fructose / Q000378:metabolism; D005837:Genitalia, Male / Q000000981:diagnostic imaging; D006801:Humans; D007248:Infertility, Male / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012661:Semen / Q000378:metabolism; D055101:Semen Analysis; D013739:Testosterone / Q000097:blood; D013959:Thyroid Diseases / Q000097:blood / Q000150:complications; D013963:Thyroid Hormones / Q000097:blood*
chemical_list: D016209:Interleukin-8; D013963:Thyroid Hormones; D005632:Fructose; D013739:Testosterone
keywords: ejaculate volume; fructose; infertile men; seminal vesicles ultrasound; thyroid hormones