From the Guidelines
Clomiphene citrate is known to increase sex hormone binding globulin (SHBG) levels in the body. When prescribed at standard doses, clomiphene works as a selective estrogen receptor modulator (SERM) that blocks estrogen receptors in the hypothalamus, leading to increased gonadotropin release (LH and FSH) 1. This stimulates testosterone production in men and ovulation in women. The increased estrogen activity that results from this hormonal cascade tends to elevate SHBG production in the liver. Higher SHBG levels can bind more testosterone, potentially reducing free testosterone availability despite increasing total testosterone.
Some key points to consider when using clomiphene citrate include:
- The medication is effective in inducing ovulation in women with polycystic ovary syndrome (PCOS), with about 80 percent of women ovulating and one half of these patients conceiving 1
- The American College of Obstetricians and Gynecologists (ACOG) recommends treatment with clomiphene citrate due to its effectiveness, based on good and consistent scientific evidence 1
- Monitoring both total and free testosterone levels during clomiphene therapy is recommended to ensure optimal treatment outcomes, particularly in men with already elevated SHBG.
It is essential to weigh the benefits and potential drawbacks of clomiphene citrate therapy, considering its effects on SHBG and testosterone levels, to provide the best possible treatment outcomes for patients.
From the Research
Clomiphene Effects on Sex Hormone Binding Globulin
- Clomiphene citrate has been shown to increase sex hormone binding globulin (SHBG) levels in various studies 2, 3, 4.
- A study published in 1981 found that SHBG concentration rose from 38.1 +/- 18.3 to 54.3 +/- 16.0 nmol/l (P less than 0.01) in oligozoospermic patients treated with clomiphene citrate 2.
- Another study published in 1995 found that clomiphene citrate increased SHBG levels by 23% in women with polycystic ovary syndrome 3.
- A systematic review and meta-analysis published in 2022 found that clomiphene citrate therapy increased SHBG levels in men with hypogonadism 4.
- However, not all studies have found a significant increase in SHBG levels with clomiphene citrate treatment. A study published in 2015 found that SHBG levels did not change significantly in hypogonadal infertile men treated with clomiphene citrate 5.
- The increase in SHBG levels with clomiphene citrate treatment may be related to the rise in estradiol (E2) levels, as suggested by a study published in 1981 2.
Mechanism of Action
- Clomiphene citrate may increase SHBG levels by stimulating the production of E2, which in turn increases SHBG production 2.
- The increase in SHBG levels may lead to a decrease in free testosterone levels, which could affect the efficacy of clomiphene citrate treatment 2.
- The mechanism of action of clomiphene citrate on SHBG levels is not fully understood and may involve complex interactions between hormones and hormone-binding proteins 2, 3, 4.
Clinical Implications
- The increase in SHBG levels with clomiphene citrate treatment may have clinical implications for the management of hypogonadism and infertility 2, 5, 4.
- Clinicians should be aware of the potential effects of clomiphene citrate on SHBG levels and monitor hormone levels regularly in patients undergoing treatment 2, 5, 4.
- Further studies are needed to fully understand the effects of clomiphene citrate on SHBG levels and to determine the clinical significance of these effects 2, 5, 4.