Letrozole in Oligospermia With Eugonadotropic-Hypogonadism and Low Testosterone Estradiol Ratio

This was a quasi-experimental study carried out from July 2023 to December 2024 in the Department of Reproductive Endocrinology and Infertility, Bangladesh Medical University. The ethical clearance was obtained from the Institutional Review Board of the Medical University (IRB approval no…..). The trial was registered with clinical trials.gov ……… The study participants were infertile male, age 20 -45 years, with oligospermia (sperm count \< 10 million/ml) or azoospermia with low serum testosterone (\<300 ng/dl), normal gonadotropin level (FSH, LH 2-7 IU/L), and low (\<10:1) testosterone to estradiol ratio. Exclusion criteria were medical and endocrine disorders, genital diseases \& genital surgery, alcohol or substance abuse, previous chemotherapy or radiotherapy, concomitant use of anticonvulsants, androgens or antiandrogen and antioxidant supplements in the previous 3 months. Informed consent was obtained from the participants.

A total of 60 eligible participants were enrolled and allocated into two groups: experimental (letrol) arm where participants received tab. letrozole 2.5 mg once daily for 3 months and control (placebo) arm where participants received placebo once daily for 3 months. During the study period, participants were contacted every month over telephone and inquired about compliance to the regimen as well as any side effects. All participants were instructed not to take any medications during the study except after consulting the physician. Second visit was scheduled at the end of 3 months to asses the treatment outcome. After 3 months of treatment, semen analysis, serum testosterone, and serum estradiol level were done. Testosterone, estradiol ratio was calculated using specific formula. Comparison was made between the effects of letrozole and placebo on sperm parameters and hormonal parameters in infertile male with eugonadotropic hypogonadism, low testerone level and low testosterone estradiol ratio. Patients were advised to timed sexual intercourse and for urinary pregnancy test in case of missed periods.

Primary outcome variable were change in sperm count, changes in the sperm motility and appearance of sperm in semen in azoospermia. Secondary outcome variables serum total testosterone level and testosterone-estradiol ratio. Total sperm count is the total number of sperm in the entire ejaculate (sperm concentration times semen volume). To calculate the total sperm count (i.e. the number of sperm cells in an individual semen sample), sperm concentration is multiplied the by the total volume of the sample. Sperm motility is the percentage of progressive \& non-progressive motility. Total motile sperm count was calculated by multiplying the concentration of sperm by the total semen volume and by the percentage of progressive motility.

Statistical analyses were carried out by using the Statistical Package for Social Sciences version 26.0 for Windows (SPSS Inc., Chicago, Illinois, USA). The mean ± SD values were calculated for continuous variables and percentages were calculated for categorical variables. Data was tested using the t-test, chi-square test as appropriate. For comparing categorical data, the Chi-square (x2) test was performed. Comparison of quantitative variables between the study groups was done using Student's t-test/unpaired t-test for independent samples when normally distributed. Paired t-test was used for quantitative variables within the group, when compared pre-treatment versus post treatment. P values \<0.05 was considered as statistically significant.