A correlative interaction between thyroid dysfunction and semen parameters in male infertility: A prospective case control study
Pubblicato online: 22 dic 2022
Pagine: 129 - 143
Ricevuto: 18 lug 2022
Accettato: 26 ago 2022
DOI: https://doi.org/10.2478/acm-2022-0015
Parole chiave
© 2022 Venkateswara Rao et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Infertility estimates ~15% of couples globally. Males are found to be solely responsible for 20-30% of infertility cases, and contribute to 50% of all cases (1). According to the Indian Society of Assisted Reproduction, infertility affects 10 to 14% of the Indian population, with higher rates in urban areas (2). In India, nearly 27.5 million couples are actively trying to conceive and suffer from infertility (3). According to the National Health Portal of India, 5% of infertility seen in Andhra Pradesh state and 15% of infertility in Kashmir state (4, 5).
Previous research shows that a significant proportion of male infertility is idiopathic, and the underlying molecular mechanisms is still unknown (6). The significant factors of male infertility are low sperm concentration (oligospermia), poor sperm motility (asthenospermia), and abnormal sperm morphology (teratospermia), and other less associated male infertility factors are semen volume and seminal markers of epididymal, prostatic, and seminal vesicle function (7, 8). Although several causes of male infertility have been identified (9), the exact aetiology and pathogenesis of male infertility remain unknown (10, 11). Infertility aetiology varies from region to region, population to population, and even locality to locality within the same population (12).
Although the effects of hyperthyroidism and hypothyroidism on female reproduction are well established, the effects of thyroid disorders on male infertility have not been extensively studied, most likely because attention in thyrotoxic males is usually focused on other manifestations of the disease, and fertility status is frequently not evaluated (13, 14). Thyroid hormones interfere with both androgen biosynthesis and spermatogenesis, either directly on Leydig and Sertoli cells or indirectly by modulating gonadotropin secretion (15). Thyroid hormones act on various cells of the male reproductive system via genomic and nongenomic mechanisms to regulate testicular testosterone secretion and the concentration of seminal plasma components such as calcium, fructose, magnesium, zinc, etc.
The optimal concentration of intratesticular testosterone promotes spermatogenesis, while other seminal properties improve sperm motility and viability and keep the sperm volume stable (16). Thyrotoxicosis can cause oligozoospermia, asthenozoospermia, and/or teratozoospermia, as well as decreased sperm volume (17). Hypothyroidism has also been associated with a decrease in serum testosterone levels. Hence, it is associated to erectile dysfunction, delayed ejaculation, hypoactive sexual desire, and poor sperm quality (18).
Hence, developing an effective preventive therapeutic intervention for male infertility necessitates a thorough understanding of the relationship between thyroid function and sperm quality. Extensive research is required to reveal the role of thyroid function and its disorders in the maintenance and deterioration of male infertility and to draw more reliable conclusions that can be used in clinical practise.
Hence, the current study investigated the relationship between thyroid hormone levels and sperm quality in a population of men recruited from an infertility clinic to detect associations between thyroid hormone levels and sperm quality and also with aetiology.
A prospective case control investigative clinical Study conducted from September 2019 to September 2022 at the department of Anatomy, Narayana Medical College, Nellore, Andhra Pradesh.
The current study was carried out by a random sampling technique selecting the infertile males those were attending to the fertility clinic.
The sample size calculation was done by formula,:
Sample size (n) = Z2 PQ/ d2
Where, Z2 value is fixed at 95% of confidence interval was 1.96,.
Prevalence (P) = 7%, i.e., 0.07 (based on previous studies)
Q = 1-P.
Error (d) is fixed at 5%., i.e., 0.05.
The sample size (n) = (1.96*1.96) *(0.07) *(0.93) / (0.05*0.05) = 0.2501 / 0.0025 = 100.04 => 100.
Therefore, the sample size = 100.
A total of 100 group I (male infertility) cases, and an age matched 100 group II subjects (fertile male) were enrolled in the study. The Institutional Ethics Committee, Narayana Medical College, Nellore, India; an approval has been taken for the study protocol. A written informed consent form was taken from all the study subjects.
Group I (case) – Infertile males who fits into the inclusion criteria.
Group II (control) – Age matched fertile males without any co-morbidities.
• Males with >24 years of age having no children for more than 2 years; even with unprotected sex and without achieving pregnancy.
• Physically and Mentally healthy males.
• Males without any congenital anomalies and co-morbidities.
• Males with prostate cancer.
• Males with erectile dysfunction.
• Males with venereal diseases.
• Males with HIV.
• Psychologically unhealthy males.
• Males with co-morbidities like diabetes (both I & II), renal pathology.
• Patients with congenital anomalies of genital organ like hypospadias.
• Klinefelters syndrome.
• Hypogondotropic hypogonadism.
• Y-chromosome microdeletion or abnormality.
• Obstructive azoospermia.
• History of treatment with Cytotoxic drugs, irradiation, or sulfasalazopyrine.
• Patients who refuse to participate in the study. :
Interviews for medical and nutritional history were part of the participant's examination.
After the detailed explanation about the procedure, the subjects were instructed to refrain from ejaculating for at least 72 hours before providing a sample of sperm. Masturbation in a clean wide mouth plastic container provided by the laboratory yielded the entire sample. The container was labelled with the patient's details, and the time and date of collection. The sample was liquefied for at least 20 minutes, but no more than 1 hour before performing a routine semen analysis, which included volume, pH, sperm concentration, sperm motility, progressive motility, and sperm morphology measurements. A fructose biochemical test was also performed. Sperm count performed using a Neubauer counting chamber and stained with Field's stain to check the sperm morphology.
Motile sperm was defined according to WHO grade as ‘A’ grade sperm (rapidly progressive with a velocity >25 μm/s at 37°C) and ‘B’ grade sperm (slow/sluggish progressive with a velocity >5 μm/s but <25 μm/s) (19).
Method for sperm motility: Morphological evaluation was carried out using an Olympus microscope and oil immersion. A coverslip was covered after placing a drop of sperm on the glass slide and examined under high power (40 ×) field. Motile spermatozoa were counted out of the 100. The percentages of motile and nonmotile spermatozoa were recorded.
Method of Sperm count: Semen was diluted 1:20 with formalin (0.1 ml semen and 1.9 ml formalin) and added the Neubauer++ chamber with diluted semen and allowed to settle for 15 minutes. The chamber was placed under the microscope and spermatozoa counted in 4 large corners squares using either 20 × or 40 × objective.
A drop of semen was placed on a glass slide, and prepared a smear, and stained the smear with field stain. Approximately 200 spermatozoa were counted under oil immersion. The percentage of normal & abnormal spermatozoa was recorded (20).
Sperm count per ml was calculated as follows:
Sperms counted (N) × correction factor for dilution (20)
= ---------------------------------------------------------------------------- × 1000 Number of squares counted (4) × volume of one square (0.1)
= N × 50000/ml.
On the same day of the sperm sample was collected, a blood sample was drawn using an aseptic technique after a 12-hour overnight fast. Sera were extracted from the blood samples. Total T3, T4, and TSH levels were assessed using Chemiluminescence Immunoassay (CLIA) assay.
The data was entered into a MS-Excel, and the statistics performed using the statistical package for Social Science Program (SPSS, IBM, US) for Windows Version 25.0. The data values for categorical variables were expressed as numbers and percentages, and the chi-square test were used to test the association between the groups. The data values for the continuous variables were expressed as mean and standard deviation, and to test mean differences between the two groups, the student's t-test was used. One-way analysis of variance (ANOVA) test was used to test mean differences among three or more groups. Pearson's correlation analysis was used to test the relationships between the parameters. All p-values less than 0.05 are considered statistically significant.
The Group I consists 100 men with a mean age of 32.4 ± 4.5 years (range: 25- 40 years), and the group II comprised of 100 men with a mean age of 31.5 ± 4.8 years (range: 25 to 40 years).
In the group I, sperm counts varied from 9 to 60 million/ml with a mean of 28.32 ± 14.60, the percentage of sperm motility varied from 15 to 70 with a mean of 40.1 ± 13.8, and the percentage of normal sperm morphology varied from 40 to 70 with a mean of 55.92 ± 5.27, Whereas in the group II, the percentage of sperm counts varied from varied from 45 to 80 million/ml with a mean of 66.5 ± 10.5, the percentage of sperm motility with a mean of 64.8 ± 7.85, and the percentage of normal sperm morphology with a mean of 83.5 ± 5.25 with a statistical difference in sperm quality between the two groups (p<0.05) (Table 1).
Out of 100 infertile male, oligozoospermia was observed in 32 cases (32%, 95% confidence interval [CI], 27.5% - 35.5%), asthenozoospermia in 48 cases (48%, 95% confidence interval [CI], 41.5% - 50.5%), and oligo-asthenozoospermia in 20 men respectively (20%, 95% confidence interval [CI], 16.85% - 22.8%).
Total T3 of oligozoospermic men ranged from 0.60 to 1.61 with mean of 115 ± 0.4, total T4 varied from 5.5 to 9.1 with a mean of 7.35 ± 1.42, and TSH (μIU/ml) ranged from 0.89 to 2.65 with a mean of 1.69 ± 0.55.
Whereas in asthenozoospermic men total T3 ranged from 0.72 to 2.65 ng/ml with a mean of 1.29 ± 0.59, total T4 varied from 6.98 to 12.8 with the mean of 9.15 ± 1.85, and TSH (μIU/ml) ranged from 1.1 to 6.75 with a mean of 2.12 ± 1.45. Only total T4 was significantly higher in asthenozoospermic men compared to those with normal sperm profiles (P<0.05), but it was still well within the normal limits.
Total T3 (ng/ml) of men with oligo-asthenozoospermia ranged from 1.12 to 1.70 with a mean of 1.25 ± 0.32, total T4 varied from 5.5 to 10.5 with the mean of 7.85 ± 1.65, and TSH ranged from 1.60 to 2.20 with a mean of 1.88 ± 0.4.
After adjusting for potential confounders, the study revealed no significant differences in sperm volume, concentration, progressive sperm motility, or morphology between the euthyroid and SCH groups (p>0.05) (Table 2) (Table 3).
Comparison of semen and thyroid profile of normal and abnormal subjects
| Characteristics | Group I (n=100 | Group II (n=100) | P value | |
|---|---|---|---|---|
| Age (Years) | Mean ± SD | 32.4 ± 4.5 | 31.5 ± 4.8 | |
| Age (yr) | 21–25 | 10% | 10% | 0.15 |
| 26–30 | 56% | 58% | ||
| 31–35 | 26% | 23% | ||
| 36–40 | 8% | 9% | ||
| Duration of active married life (yr) | 2–3 | 35 | 34 | 0.26 |
| 3.1–5 | 33 | 30 | ||
| 5.1–7 | 20 | 18 | ||
| 7.1–9 | 8 | 10 | ||
| 9.1–15 | 4 | 8 | ||
| Semen analysis : Quantity (c.c.) | <1 2 | 16 57 | 2 63 | 0.0001* |
| 2.1-3 | 16 | 15 | ||
| >3 | 12 | 20 | ||
| Semen analysis : Sperm density (million/ml) | >15 | 48 | 100 | - |
| 10.1 – 15 | 29 | 0 | - | |
| <10 | 23 | 0 | - | |
| Semen analysis : Sperm motility | Actively motile | 32 | 100 | - |
| Sluggishly motile | 40 | 0 | - | |
| Non-motile | 28 | 0 | - | |
| Semen analysis : Frequency of motile sperm % | >50 | 22 | 100 | - |
| 20.1-50 | 48 | 0 | - | |
| 5-20 | 30 | 0 | - | |
| Semen analysis : Pus cell/HPF | >10 | 16 | - | - |
| 4-10 | 29 | - | - | |
| 2-3 | 55 | 10 | - | |
| Sperm count (106/ml) | Mean ± SD | 28.32 ± 14.60 | 66.5 ± 10.5 | <0.0001* |
| Sperm motility (%) | Mean ± SD | 40.1 ± 13.8 | 64.8 ±7.85 | 0.0045*0.03 |
| Normal morphology (%) | Mean ± SD | 55.92 ± 5.27 | 83.5 ± 5.25 | 8* |
| Total T3 (ng/ml) (0.45 – 1.95) | Mean ± SD | 1.29 ± 0.54 | 1.15 ± 0.55 | 0.25 |
| Total T4 (μg/dl) (4.2 – 9.8) | Mean ± SD | 8.42 ± 1.82* | 7.2 ± 3.2 | 0.02* |
| TSH (μIU/ml) (0.40 – 5.55) | Mean ± SD | 1.98 ± 1.3 | 2.11 ± 1.2 | 0.14 |
p<0.05
Thyroid status of infertile men
| Euthyroid (n=69) | Subclinical hypothyroidism (n=31) | P value | |
|---|---|---|---|
| Suspected hypothyroidism | 19 | 21 | - |
| Obstructive sleep apnoea | 8 | 4 | - |
| Bipolar affective disorders | 6 | 6 | - |
| Headache | 3 | 1 | - |
| Constipation | 6 | 5 | - |
| Speech problems | 1 | 2 | - |
| Oligospermia | 8% | 9% | 0.40 |
| Asthenozoospermia | 7% | 6% | |
| Oligo-asthenoteratospermia | 24% | 20% | |
| Total motile sperm count | 27.5 ± 19.7 x 106 | 26.8 ± 18.4 x 106 | 0.10 |
| Semen volume, mL | 2.9 [1.0–3.2] | 2.6 [1.2–3.6] | 0.45 |
| Sperm motility, % | 42.5 [32.9–37.5] | 37.2 [30.3–36.1] | 0.20 |
| Sperm morphology, % | 47.5 [40.2–60.5] | 30.5 [28.5–55.5] | 0.12 |
| Thyroid profile | 1.38 ± 0.44 | 1.45 ± 0.65 | 0.25 |
| Total T3(ng/ml) | 9.2 ± 1.90 | 8.66 ± 1.7 | 0.02* |
| Total T4 (μg/dl) | |||
| TSH (μIU/ml) | 1.89 ± 1.1 | 2.32 ± 1.5 | 0.043* |
Comparison of thyroid profile, and risk factors in group I and group II subjects
| Group I | Group II | ||||
|---|---|---|---|---|---|
| Ollgozoospermla (n=32) | Asthenozoospermla (n=48) | Oligo-asthenozoospermia (n=20) | |||
| Total T3( ng/ml) | Mean ± SD | 1.15 ± 0.4 | 1.29 ± 0.59 | 1.25 ± 0.32 | 1.2 ± 0.40 |
| Total T4 (μg/dl) | Mean ± SD | 7.35 ± 1.42 | 9.15 ± 1.85* | 7.85 ± 1.65 | 7.2 ± 2.15 |
| TSH (μlU/ml) | Mean ± SD | 1.69 ± 0.55 | 2.12 ± 1.45 | 1.88 ± 0.40 | 2.1 ± 1.20 |
| BMI- | Normal | 19 | 22 | 11 | 71 |
| Overweight | 8 | 14 | 7 | 21 | |
| Obese | 5 | 12 | 2 | 8 | |
| Varicocele | 7 | 14 | 6 | 0 | |
| Alcoholic | Mild | 5 | 4 | 4 | 7 |
| Moderate | 3 | 2 | 2 | 2 | |
| Heavy | 2 | 1 | 1 | 2 | |
| Smoker | Light Smokers | 6 | 4 | 4 | 8 |
| Moderate Smokers | 4 | 2 | 2 | 3 | |
| Heavy Smokers | 2 | 2 | 2 | 2 | |
Mild alcohol: consuming 40g or less; Moderate alcohol: consuming 40-80g; and Heavy alcohol: consuming more than 80g per day. Light Smokers: 01-10 cigarettes/day; Moderate Smokers: 11-20 cigarettes/day; and Heavy Smokers: >21 cigarettes/day.
Total 30% patients were having smoking habit in the infertile male group. 16 out of 30 smo - ker had >50% motility while 14 had a motility of <5%. Also 20 patients of the smoking group had <10% of morphologically normal sperm. Oligozoospermia was present in as high in the alcoholics than in the nonalcoholic cases. All three abnormalities like oligo-asthenozoospermia, asthenozoospermia, and oligozoospermia were seen in 32 patients of the alcoholic group.
10 out of 19 obese patients had sperm motility <5%. Totally, 27 patients were found varicocele, among them 14 had asthenozoospermia, 7 had oligozoospermia, and 6 had oligo-asthenozoospermia.
We evaluated diagnostic accuracies of investigative parameters using ROC curve analysis to predict the accurate value for male infertility occurrence (Table 4). ROC analysis between the group I vs the group II showed a significant increase in sperm count in the group I than the group II, however increase in sperm count was not linear (Figure 1. a). Comparative ROC analysis showed a linear response for cases with >28.32 sperm count vs <28.32 million/ml of Sperm count (Figure 1. b.). ROC analysis did not show a linear response for sperm motility in cases with >40.1, sperm motility vs <40.1% (Figure 1. d). ROC analysis did not show a significant change in normal morphology in the group I compared to the group II (Figure 1.e). Comparative ROC analysis did not show a linear response for normal morphology of >55.92 in the group I, and <55.92 in the group II (Figure 1.f.).
ROC analysis did not show a significant change in total T3 levels in the group I compared to the group II (Figure 2.a.). Comparative ROC analysis did not show a linear response for Total T3 levels in cases with >1.29 Total T3 vs <1.29 Total T3 levels (Figure 2.b). ROC analysis did not show a significant change in total T4 levels in the group I compared to the group II (Figure 2c.). Comparative ROC analysis did not show a linear response for total T4 levels in cases with >8.42 Total T4 vs <8.42 Total T4 levels (Figure 2.d.). ROC analysis did not show a significant change in TSH levels in the group I compared to the group II (Figure 2.e.). Comparative ROC analysis did not show linear response for TSH levels in cases with >1.98 TSH vs <1.98 TSH levels (Figure 2.f.).
Table 5 shows the Pearson correlation analysis of blood thyroid profile with seminal parameters. There were inverse correlations of thyroid profile with sperm count, sperm motility, and normal sperm morphology. There were significant (p<0.01) inverse correlations of serum TSH levels with sperm volume (r= -0.12, p= 0.02), sperm motility (r= -0.26, p= 0.02), and sperm morphology(r= -0.304, p= 0.02). There was a significant correlation seen between Serum T4 levels and sperm count (r= -0.278, p= 0.02), and serum T4 levels and sperm motility (r= -0.249, p= 0.032).
ROC analysis showing Area under the ROC Curve (AUC), sensitivity and specificity of different parameters
| Sperm count | 0.7860 | 87.50 | 50.80 |
| Total T3 | 0.5315 | 50.46 | 52.31 |
| Normal morphology | 0.6390 | 72.36 | 42.63 |
| Sperm motility | 0.7110 | 69.85 | 50 |
| Total T3 | 0.5030 | 46.91 | 54.23 |
| TSH | 0.5740 | 50 | 57.78 |
| Cases with Sperm motility < 40.1 vs Sperm motility > 40.1 | |||
| Sperm count | 1.000 | 93.75 | 68.95 |
| Total T3 | 0.5882 | 57.91 | 50.09 |
| Normal morphology | 0.5579 | 48.35 | 60.06 |
| Sperm motility | 0.5671 | 57.91 | 48.03 |
| Total T3 | 0.6278 | 58.54 | 51.96 |
| TSH | 0.5570 | 62.17 | 44.27 |
Pearson correlation of Total T3, T4, and TSH levels with semen parameters in infertile men
| Semen volume (ml) | -0.147 | 0.22 | -0.095 | 0.430 | -0.12 | 0.02 |
| Sperm count (×106 cells/ml) | -0.150 | 0.32 | -0.278 | 0.020 | -0.26 | 0.22 |
| Sperm motility (%) | -0.091 | 0.42 | -0.249 | 0.032 | -0.26 | 0.02 |
| Morphology (%) | -0.079 | 0.45 | 0.160 | 0.130 | -0.304 | 0.02 |
Fig 1
a. ROC of sperm count between the group I and the group II. b. ROC of sperm count levels between the cases with sperm count <28.32 to >28.32. c. ROC of sperm motility levels between the group I and the group II. d. ROC of sperm motility levels between the cases with sperm motility value >40.1, and <40.1. e. ROC of normal morphology levels between the group I and the group II. f. ROC of Normal morphology between the cases with normal morphology value >55.92 and <55.92.
Fig 2
a. ROC of total T3 levels between the group I and the group II. b. ROC of total T3 levels between the cases with total T3 value >1.29 and <1.29. c. ROC of total T4 levels between the group I and the group II. d. ROC of total T4 levels between the cases with total T4 value >8.42 and <8.42 .e. ROC of TSH between the group I and the group II. f. ROC of TSH between the cases with TSH value >1.98 and <1.98.
Although several causes of male infertility have been identified, the exact aetiology and pathogenesis of approximately half of all male infertility cases remains unknown.
Oligozoospermia was found in 32 (32%, 95% confidence interval [CI], 27.5% - 35.5%), asthenozoospermia in 48 (48%, 95% confidence interval [CI], 41.5%- 50.5%), and oligoasthenozoospermia in 20 men in our study of 100 abnormal subjects (20%, 95% confidence interval [CI], 16.85% - 22.8%). Sharma et al., were also observed the similar results (21).
In the current study, it was observed that the majority of subjects were from urban areas, possibly due to pollution or lifestyle-related factors such as stress and other factors that may affects male fertility. In this study, the age range for presentation was 24 to 39 years, with a mean age of 32.4 ± 4.5 years.
In the current study, 35% had 2 to 3 years of active married life, and 33% had 4 - 5 years of active married life, with a mean of 5.1years. After 6 years of active married life, this was reduced to 5% in patients with 2 years of active married life. Hence, the shorter the duration of male infertility, had the better the prognosis.
It was observed that 16 of 30 smokers had a motility of more than 50%, while 14 had a motility of less than 5%. Sperm motility was less than 5% in 8 percent of light smokers, 4% of moderate smokers, and 4 percent of heavy smokers. This study was comparable to that of Zhang et al., (22) and Tandel and Patel (23).
Zukerman et al., also reported that Oligo-asthenozoospermia, asthenozoospermia, and oligozoospermia in 32% of alcoholics (24). Villalta`s study showed that Oligo-asthenozoospermia, asthenozoospermia, and oligozoospermia in 15% of smokers and 72% in non-alcoholics (25).
In our study, 10 of 19 obese patients had 5% sperm motility. While 4 out of 29 overweight patients and 4 out of 52 normal weight patients had 50% sperm motility, normal weight patients had 50% sperm motility. Korte et al., observed that men with a high BMI (>25) have a low number of normal-motile sperm cells (26).
Infection of the male reproductive tract is represented by the presence of >4 pus cells in the sperm. A pus cell count of 4-10 pus cells/HPF indicated a moderate infection in 29% of patients, and >10 pus cells/HPF indicated a severe infection in 16% of patients in our study. According to Saxena, 20% of cases had severe infections (27).
In our study, 27% of the cases had varicocele, 14% had asthenozoospermia, 7% had oligospermia, and 6% had oligo-asthenozoospermia. Ali study showed 36% asthenozoospermia, 25% oligospermia, and 21% teratozoospermia (28, 29).
Thyroid hormone levels have been shown to correlate positively with serum testosterone levels. This condition is associated to a number of male reproductive disorders, including hypoactive sexual behaviour, erectile dysfunction, delayed ejaculation, and poor sperm quality (30). Various studies have described an association between the hypothyroidism and male infertility, but it is unclear that hypothyroidism may directly affects the sperm quality (31-34).
In our current study, 31% of the subjects had a subclinical hypothyroidism. Subclinical thyroid dysfunction was associated with an altered sperm count but not sperm motility or morphology. This finding is consistent with the findings of other studies (35).
There were inverse correlations of thyroid profile with sperm count, sperm motility, and normal sperm morphology. There were significant (p < 0.01) inverse correlations of serum TSH levels with sperm volume (r= -0.12, p= 0.02), sperm motility (r= -0.26, p= 0.02), and sperm morphology(r= -0.304, p= 0.02). Similarly, serum T4 levels were significantly (p<0.01) correlated with sperm count (r= -0.278, p= 0.02), and sperm motility (r= -0.249, p= 0.032).
Both hyperthyroidism and hypothyroidism affects the testicular function and neuroendocrine regulation of reproductive functions via the hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-gonadal (HPG) axis crosstalk. TSH is critical in the regulation of the HPT axis. The HPG axis normally regulates testicular function. Thyroid hormones work biologically by binding to two nuclear thyroid hormone receptors (TRs): TR and THR. Thyroid hormones are also important in the initiation of Leydig cell differentiation before puberty (36).
T3 binds to TRs on postpubertal Sertoli cells, inhibiting the synthesis of aromatase and androgen-binding protein, as well as modulating testosterone conversion to 17-estradiol and testosterone concentration in the seminiferous tubules. Thyroid hormones promote testosterone steroidogenesis in adult Leydig cells by activating the steroidogenic acute regulatory (StAR) protein, which is involved in cholesterol transport into the mitochondria (31).
Many conditions may influence the sperm quality of males. Oxidative stress is well-known to be harmful to sperm quality, primarily by causing DNA damage in sperm cells. Thyroid hormone physiological ranges regulate metabolism, including cell oxygen consumption, and both hyperthyroidism and hypothyroidism are associated with oxidative damage.
A low sperm volume was reported in a small series of subclinical hypothyroidism (n =31); in our study, no subjects were overtly hypothyroid/hyperthyroid, though a few had lower TSH levels (32, 33).
In our study, the mean T3, T4, and TSH levels in infertile male subjects were 1.29 ± 0.54 ng/ml, 8.42 ± 1.82 g/dl, and 1.98 ±1.3 IU/ml, respectively. Within the normal range of TSH values, the relationship of TSH with the sperm parameters was more pronounced in our study. In our study, 31% of the subjects had subclinical hypothyroidism and lower sperm counts. In other studies, 24-25% of hypothyroid subjects had lower sperm counts, with no significant difference in sperm volume (34-38).
In the current study, total T3 of oligozoospermic men with a mean of 115 ± 0.4 ng/ml, total T4 with a mean of 7.35 ± 1.42 μg/dl, and TSH with a mean of 1.69 ± 0.55 IU/ml, whereas in asthenozoospermic men total T3 with mean of 1.29 ± 0.59 ng/ml, total T4 with the mean of 9.15 ± 1.85 μg/dl, and TSH ranged with mean of 2.12 ± 1.45 IU/ml.
Clyde et al. (39) studied three young thyrotoxic males and observed that two had marked oligozoospermia with a decreased motility and the third had borderline low sperm counts with a decreased motility. Kidd et al. (40) studied Grave's disease patients and observed that four of the five had total sperm counts less than 40 million/ml and only one had sperm density less than 24 million/ml.
Furthermore, total T4 was found to be significantly higher in men with asthenozoospermia, but no relationship between T3 and/or TSH and oligozoospermia, asthenozoospermia, or oligoasthenozoospermia was found, which is consistent with Kumar et al. (19).
Our findings are consistent with the findings of Lotti et al. (18), who observed that euthyroid subjects (n=145) had lower semen volumes compared to those with subclinical hyperthyroidism (n=6) and higher than those with subclinical hypothyroidism (n=12); however, no relationship between the semen parameters and TSH was found. Thyroid function abnormalities appear to have the most significant effect on sperm parameters, namely impaired motility and/or morphology (41).
Hence, the most noticeable effect of thyroid function abnormalities on sperm parameters was impaired motility and/or morphology. Based on our findings, we concluded that the relationship between TSH and sperm volume/count was stronger.
Smoking, obesity, and infection all reduce fertility by lowering sperm count, motility, and changing the morphology of sperm. We observed a significant relationship between TSH and sperm volume and motility. These findings suggest that normal thyroid function is a component of good sperm quality.