Ceiling effect of clomiphene citrate on the testosterone to estradiol ratio in eugonadal infertile men

Abstract

Introduction The testosterone to estradiol ratio (T/E2 ratio) reportedly exerts a stronger effect on semen quality and sexual desire than does testosterone alone. Clomiphene citrate is a selective estrogen receptor modulator that has long been used as an empirical treatment option in the management of idiopathic oligozoospermia. Clomiphene may change the hypothalamus–pituitary–gonad axis and result in the alteration of the T/E2 ratio. No reliable data are available regarding the change in the T/E2 ratio after clomiphene use in eugonadism. Methods This study included 24 male patients who were diagnosed with idiopathic infertility with eugonadism. They all received clomiphene citrate (25 mg/day) as empirical treatment. Blood tests for serum testosterone, estradiol, prolactin, luteinizing hormone, and follicle stimulating hormone were performed before and after 4 weeks of clomiphene use. Paired t-tests were used to evaluate the significance of the hormone level change. Results Overall, the patients’ T/E2 ratio did not increase significantly after clomiphene use. In the subgroup analysis, the T/E2 ratio of patients with a baseline ratio of <200 increased significantly after clomiphene use. Conclusions Clomiphene citrate may significantly increase the T/E2 ratio in eugonadal men under the premise of its ceiling effect (T/E2 ratio < 200), providing practitioners with guidance on the use of clomiphene in this demographic.

Evaluation of Ovarian Histomorphology and Function Following Clomiphene Citrate and Human Chorionic Gonadotropin Administration in Wistar Rats

“…This indicates that clomiphene citrate can stimulate the ovaries to secrete more estrogen, which is crucial for the IDEMUDIA, O. U; ATAMAN, J. E menstrual cycle and pregnancy (Liao et al 2022). Moreover, high levels of estradiol have been suggested to cause irregular periods and may worsen conditions that affect reproductive health, such conditions include PCOS (Cleveland Clinic 2022b) This could potentially make clomiphene citrate detrimental to reproductive health (Liao et al 2022). A previous study by Hussein et al (2017), reported an increase in estradiol level on the day HGC was administered, thus suggesting that HGC could be responsible for the increased level of estradiol.…”

“…Estradiol level was significantly higher in groups B, C, and D compared to the control group. This indicates that clomiphene citrate can stimulate the ovaries to secrete more estrogen, which is crucial for the IDEMUDIA, O. U; ATAMAN, J. E menstrual cycle and pregnancy (Liao et al 2022). Moreover, high levels of estradiol have been suggested to cause irregular periods and may worsen conditions that affect reproductive health, such conditions include PCOS (Cleveland Clinic 2022b) This could potentially make clomiphene citrate detrimental to reproductive health (Liao et al 2022).…”

A proprietary blend of standardized Punica granatum fruit rind and Theobroma cocoa seed extracts mitigates aging males' symptoms: A randomized, double-blind, placebo-controlled study

“…An interesting observation from the present study is a significantly increased TT/E2 ratio in the LN18178 supplemented subjects. It is worth noting that a positive correlation exists between the TT/E2 ratio and increased sexual desire, semen quality, and libido in men 40 . Therefore, the improved score in the sexual behavior domain of the AMS questionnaire in association with increased testosterone level in the herbal supplemented subjects is noteworthy.…”

Clomiphene citrate treatment during perinatal development alters adult partner preference, mating behaviour and androgen receptor and vasopressin in the male mandarin vole Microtus mandarinus

“…Androgen receptors are blocked by clomiphene citrate. However, we think that clomiphene citrate might also have an indirect effect on androgen receptors because clomiphene citrate, an oestrogen receptor blocker or anti-oestrogen, might downregulate ERs through the ubiquitin-proteasome pathway (Amita et al, 2016), Furthermore, clomiphene may change the hypothalamus-pituitary-gonad axis, resulting in alteration of the T/oestradiol ratio (Liao et al, 2022), while T normally acts through ERs to upregulate AR (Zuloaga et al, 2008). Therefore, we suggest that exposure to clomiphene citrate during development reduces the expression of oestrogen receptors, thereby reducing the expression of AR in MT male brain regions related to sexual behaviour by antagonizing the activity of the oestrogen receptor.…”