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Effect of chronic aromatase inhibition by delta 1-testolactone on pituitary-gonadal function in oligozoospermic men
Abstract:
Aromatase inhibition by delta 1-testolactone (Teslac, 500 mg twice daily) for 6 months in 9 patients with idiopathic oligozoospermia lowered the levels of serum estradiol (E2) and thereby sex hormone binding globulin (SHBG) (rS = +0.40, p less than 0.025) to values -35 and -25%, respectively, below the pretreatment values (P less than 0.001 and less than 0.005). The E2 decrease was accompanied by a temporary increase (+50%) in the levels of follicle stimulating hormone (FSH), not of luteinizing hormone (LH), and of 17 alpha-hydroxyprogesterone (17 alpha-OHP), but less of testosterone (T) (+30%), which led to a transient rise in the 17 alpha-OHP/T ratio. The T/E2 ratio and "free T" index (T/SHBG) almost doubled until the end of the treatment period. During delta 1-testolactone treatment the mean sperm density gradually rose from 8.1 +/- 1.3 (SEM) before to 21.3 +/- 6.7 X 10(6)/ml after 6 months (P less than 0.01), whereas the total sperm count almost threefold increased (P less than 0.05). Sperm concentrations exceeding 20 X 10(6)/ml were achieved in 4 of the 9 patients. Two of these patients' wives became pregnant. Although the data point to a pivotal role of estrogens in the pathogenesis of the spermatogenic lesion in some patients with idiopathic oligozoospermia, the lack of a beneficial effect of estrogen lowering in others points to a multicausal nature of the disease entity.
Insights
Aromatase inhibition using delta 1-testolactone improved sperm parameters in men with idiopathic oligozoospermia by reducing estradiol levels. This suggests a role for estrogens in male infertility, though other factors may also be involved.
Area of Science:
- Reproductive Endocrinology
- Male Infertility Research
- Pharmacological Intervention
Background:
- Idiopathic oligozoospermia is a complex condition affecting male fertility.
- Elevated estrogen levels may contribute to impaired sperm production in some men.
- Aromatase inhibitors offer a potential therapeutic strategy by modulating hormone levels.
Purpose of the Study:
- To investigate the effects of delta 1-testolactone, an aromatase inhibitor, on hormonal profiles and sperm parameters in patients with idiopathic oligozoospermia.
- To assess the potential role of estrogen reduction in improving sperm quality and fertility outcomes.
Main Methods:
- Nine patients with idiopathic oligozoospermia received delta 1-testolactone (500 mg twice daily) for six months.
- Serum levels of estradiol (E2), sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17 alpha-hydroxyprogesterone (17 alpha-OHP), and testosterone (T) were monitored.
- Sperm density and total sperm count were assessed before and after treatment.
Main Results:
- Delta 1-testolactone significantly reduced serum estradiol (-35%) and SHBG (-25%) levels.
- Follicle-stimulating hormone (FSH) and 17 alpha-hydroxyprogesterone (17 alpha-OHP) levels temporarily increased, while testosterone (T) showed a moderate increase (+30%).
- Mean sperm density increased from 8.1 to 21.3 x 10(6)/ml (P < 0.01), and total sperm count nearly tripled (P < 0.05).
- Four patients achieved sperm concentrations >20 x 10(6)/ml, and two achieved pregnancies.
Conclusions:
- Aromatase inhibition with delta 1-testolactone can improve sperm parameters in a subset of men with idiopathic oligozoospermia.
- Estrogens play a significant role in the pathogenesis of spermatogenic dysfunction in some cases.
- The multifactorial nature of idiopathic oligozoospermia is highlighted by the varied response to estrogen-lowering therapy.