Comparative characteristics of endocrine profile in males with infertility as well as in adolescents with varicocele

Introduction. Male infertility poses a pressing issue due to escalating prevalence of males with reproductive system diseases, the most common among which is varicocele being diagnosed in childhood and adolescence. Measuring level of hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and estradiol is the key element while assessing the reproductive male potential.

Aim: to compare the parameters of hormonal status in adolescents with varicocele as well as males with diagnosed infertility and identify predictors of hypogonadism in pubertal period.

Materials and Methods. Males with diagnosed infertility as well fertile males underwent a single measurement of serum FSH, LH, testosterone and estradiol levels. Adolescents with/without varicocele were measured the serum hormones noted above in dynamics annually between studies for the period within the 14 to 17 years of age. The data obtained were compared in infertile and fertile males, adolescents with/without varicocele, as well as assessed hormone status between different age groups in both cohorts and adolescents aged 17 years.

Results. Our study allowed to identify significant differences in hormone level in male patients with infertility and varicocele lacking reproductive pathology. Infertile males had significantly higher levels of LH and estradiol (for both: p < 0.001). The LH level in infertile vs. fertile males was 5.01 ± 2.69 IU/L vs. 3.40 ± 1.17 IU/L, respectively, whereas estradiol level was 136.51 ± 92.79 pmol/l and 82.49 ± 48.33 pmol/l, respectively that might indicate at lowered testosterone level. Fifteenand sixteen-year-old-adolescents with varicocele had significantly lower LH level: 15 years old – 3.72 ± 1.92 IU/L vs. 2.71 ± 1.65 IU/L (p < 0.0123) in subjects without vs. with varicocele; 16 years old – 3.42 ± 1.16 IU/L vs. 2.81 ± 1.66 IU/L (p < 0.0381) in subjects without vs. with varicocele. It may account for decreased testosterone level. Active puberty in adolescents is accompanied by dynamically increased testosterone levels. Starting from the age of 15 years, adolescents with varicocele had significantly increased testosterone level in each subsequent age group. Thus, at 14 and 15 years of age, testosterone level in adolescents with varicocele was 10.61 ± 4.70 nmol/l and 13.60 ± 5.64 nmol/l (p < 0.0001), respectively, whereas at 16 and 17 years of age it continued to rise reaching 16.65 ± 6.44 nmol/l (p < 0.001) and 19.22 ± 7.36 nmol/l (p < 0.0160), respectively. In contrast, age-matched adolescents without varicocele had significantly elevated testosterone level solely at age of 15 vs. 14 years. Whereas at 14 years of age testosterone level in comparison group was 15.73 ± 7.2 nmol/l, at 15 years of age it was significantly increased up to 21.45 ± 9.51 nmol/l (p < 0.0113). In the subsequent age categories of this group, no significant difference in testosterone level was found. While comparing such parameter between the main and control adolescent groups, testosterone level was significantly higher in adolescents lacking varicocele at the age of 14, 15 and 16 years compared with age-matched subjects with varicocele. At 14 years of age, testosterone level in adolescents without/with varicocele was 15.73 ± 7.2 nmol/l vs. 10.61 ± 4.7 nmol/l (p < 0.0007), respectively, at 15 years of age – 21.45 ± 9.57 nmol/l vs. 13.60 ± 5.64 nmol/l (p < 0.0001), respectively, at 16 years of age – 20.02 ± 5.84 nmol/l vs. 16.65 ± 6.44 nmol/l (p < 0.0268), respectively. The FSH level in infertile males and adolescents with varicocele was 5.16 ± 2.67 IU/L and 4.1 ±

2.63 IU/L (p < 0.0081), whereas LH level was 5.01 ± 2.69 IU/L and 2.76 ± 1.65 IU/L (p < 0.04), respectively. In adolescents with varicocele and infertile males, estradiol level was 177.45 ± 70.63 pmol/l and 136.51 ± 92.79 pmol/l (p < 0.001), respectively. While comparing hormone levels in fertile males and adolescents lacking varicocele, a significantly higher estradiol level was found in adolescents 181,87 ± 27.14 pmol/l vs. 82.49 ± 48.33 pmol/l (p < 0.001).

Conclusion. A study of the hormonal status in infertile vs. fertile males revealed decreased testosterone production accompanied with higher levels of LH and estradiol. Due to profound changes in LH and testosterone levels detected in adolescents with varicocele as well as in infertile males, it is plausible that such hormones may serve as predictors of hypogonadism in the pubertal period. Adolescents with varicocele taking into consideration progressive course of the disease and verified lower testosterone level require further monitoring of hormone level to prevent endocrine infertility.

1. Apolikhin O.I., Moskaleva N.G., Komarova V.A. Contemporary demographic situation and problems of improving the reproductive health of Russian population. [Sovremennaya demograficheskaya situaciya i problemy uluchsheniya reproduktivnogo zdorov'ya naseleniya Rossii]. Eksperimental'naya i klinicheskaya urologiya. 2015;(4):4–14. (In Russ.).

2. Shirshov V.N. Current state of the male infertility problem: the review of European Association of Urology clinical guidelines. [Sovremennoe sostoyanie problemy muzhskogo besplodiya: obzor klinicheskih rekomendacij evropejskoj associacii urologov]. Klinicheskaya praktika. 2016;(1):39–49. (In Russ.).

3. Osipova A.M., Dekhtiar S.K., Tarusin D.I. The importance of evaluating inhibitor B in boys-teenagers with diseases of irreproductive system. [Znachimost' opredeleniya koncentracii ingibina V v krovi u yunoshejpodrostkov s zabolevaniyami organov reproduktivnoj sistemy]. Kremlevskaya medicina. Klinicheskij vestnik. 2016;(3):110–3. (In Russ.).

4. Khayrutdinov K.N., Sitdykova M.Z., Zubkov A.Yu. Male infertility is the problem of XXI century. [Muzhskoe besplodie – problema XXI veka]. Prakticheskaya medicina. 2018;(6):185–9. (In Russ.).

5. Guseva O.E., Loschenko M.A., Lebedko O.A., Anufrieva A.V. Some parameters of the reproductive status of adolescent males with obesity. [Nekotorye parametry reproduktivnogo statusa mal'chikov podrostkov s ozhireniem]. Dal'nevostochnyj medicinskij zhurnal. 2016;(3):69–74. (In Russ.).

6. Solodilova E.A., Kondratyeva E.I., Kravets E.B., Gorbatenko E.V. Peculiarities of puberty in boys with obesity. [Osobennosti polovogo sozrevaniya u mal'chikov s ozhireniem]. Kubanskij nauchnyj medicinskij vestnik. 2011;(3):158–64. (In Russ.).

7. Evdokimov V.V., Zakharikov S.V., Kastrikin Yu.V. The varicocele in children and adolescents. [Varikocele u detej i podrostkov]. Lechenie i profilaktika. 2017;(1):53–6. (In Russ.).

8. Kodirova A.M., Negmatova M.N. Polyetiology of male infertility. Medical culture. [Polietiologichnost' muzhskogo besplodiya. Medicinskaya kul'tura]. Elektronnyj nauchno-obrazovatel'nyj vestnik «Zdorov'e i obrazovanie v XXI veke». 2017;19(12):138–40. (In Russ.).

9. Alkaram A., McCullough A. Varicocele and its effect on testosterone: implications for the adolescent. Transl Androl Urol. 2014;3(4):413–7. https://doi.org/10.3978/j.issn.2223-4683.

10. Kalinina S.N., Korenkov D.G., Fesenko V.N. Treatment of spermatologic disorders and oxidative stress after reproductively significant diseases caused by sexually transmitted infections. [Lechenie spermatologicheskih narushenij i oksidativnogo stressa posle perenesennyh reproduktivno znachimyh zabolevanij, vyzvannyh infekciyami, peredayushchimisya polovym putem]. Urologicheskie vedomosti. 2018;8(4):5–14. (In Russ.). https://doi.org/10.17816/uroved845-15.

11. Dabaja A.A., Goldstein M. When is a varicocele repair indicated: the dilemma of hypogonadism and erectile dysfunction? Asian J Androl. 2016;18(2):213–6. https://doi.org/10.4103/1008-682X.169560.

12. Zhiborev B.N. Varicocele, male hypogonadism and reproductive prognosis. [Varikocele, muzhskoj gipogonadizm i reproduktivnyj prognoz]. Rossijskij mediko-biologicheskij vestnik imeni akademika I.P. Pavlova. 2008;16(2):7–14. (In Russ.).

13. Komarova S.Yu., Tsap N.A. Ways to reduce the risk of reproductive loss in children with varicocele. [Puti snizheniya riska reproduktivnyh poter' u detej s varikocele]. Medicinskaya nauka i obrazovanie na Urale. 2017;(1):98–101. (In Russ.).

14. Kucherov V.A., Kravtsov Yu.A., Matveev S.V. Opportunities and prospects of the intraoperative study of sex hormones with varicocele. [Vozmozhnosti i perspektivy intraoperacionnogo issledovaniya polovyh gormonov pri varikocele]. Ural'skij medicinskij zhurnal. 2018;(5):100–5. (In Russ.).

15. Cho C.L., Esteves S.C., Agarwal A. Indications and outcomes of varicocele repair. Panminerva Med. 2019;61(2):152–63. https://doi.org/10.23736/S0031-0808.18.03528-0.

16. Shevyrin A.A. Modern view on treatment of male infertility. [Sovremennyj vzglyad na lechenie narushenij muzhskoj fertil'noj funkcii]. RMZh. Medicinskoe obozrenie. 2018;2(12):30–5. (In Russ.).

17. Nishlag E., Bere G.M. Andrology. Male health and reproductive dysfunction. Eds. E. Nishlag and G.M. Bere. Moscow: MIA, 2005. 551 p. (In Russ.).

18. Barati E., Nikzad H., Karimian M. Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management. Cell Mol Life Sci. 2020;77(1):93–113. https://doi.org/10.1007/s00018-019-03253-8.

19. Shiraishi K., Matsuyama H. Effects of medical comorbidity on male infertility and comorbidity treatment on spermatogenesis. Fertil Steril. 2018;110(6):1006–11.e2. https://doi.org/10.1016/j.fertnstert.2018.07.002.

20. Busetto G.M., Del Giudice F., Virmani A. et al. Body mass index and age correlate with antioxidant supplementation effects on sperm quality: post hoc analyses from a Double-Blind Placebo-Controlled Trial. Andrologia. 2020;52(3):e13523. https://doi.org/10.1111/and.13523.

21. Al-Adl A.M., El-Karamany T., Issa H., Zaazaa M. The influence of antisperm antibodies, intratesticular haemodynamics and the surgical approach to varicocelectomy on seminal variables. Arab J Urol. 2014;12(4):309–17. https://doi.org/10.1016/j.aju.2014.07.001.