Q. I am already on enclomiphene to increase testosterone while preserving fertility. Can I use it with any other meds that will support fertility goals even further?
A. Yes. Low dose gonadorelin or hCG are often used in men on exogenous testosterone to help protect from fertility collapse. But keep in mind that gonadorelin and hCG can also be used in men on enclomiphene to further augment fertility.
Q. I want to get the most out of enclomiphene. Will I get a stronger effect using it on all 7 days of a week?
A. Enclomiphene may exert more favorable benefits if cycled 5 days out of 7 (or every other day). Enclomiphene opposes estrogen receptors in the hypothalamus to induce a cascade of downstream effects. However, whenever a biological signal is present for prolonged periods, it may potentially down-regulate the receptors it acts upon. Cycling the enclomiphene is a best-practice to ensure the medication does not weaken over time.
Q. I understand enclomiphene is frequently used in men with fertility aspirations in place of testosterone replacement. Are there other clinical reasons someone might choose enclomiphene?
A. Testosterone replacement can be administered within physiologic ranges; however, some patients remain cautious about direct hormonal replacement. Testosterone replacement may be associated with changes in clinical markers such as hematocrit, prostate-specific antigen (PSA), and serum lipid levels, which is why routine monitoring is typically recommended.
Enclomiphene works by stimulating the body’s endogenous production of testosterone rather than providing exogenous hormone. In clinical studies, enclomiphene has generally maintained testosterone levels within physiologic ranges and has shown minimal impact on certain serum biomarkers. By supporting endogenous testosterone production within normal ranges, enclomiphene may help limit the likelihood of side effects sometimes associated with supraphysiologic testosterone levels, such as acne or hirsutism.4
Q. You also offer a Test Booster that appears comparable to enclomiphene. How do these options differ, and which one might be most appropriate for my situation?
A. The SERM used in Test Booster is clomiphene, which is a racemic mixture of both enclomiphene and zuclomiphene. Whereas enclomiphene exerts desirable pharmacological effects, zuclomiphene is responsible for estrogenic side effects. As such, enclomiphene exhibits a more favorable adverse effect profile than clomiphene.2,3 Furthermore, when zuclomiphene was administered in isolation, it adversely affected testicular histology such as Leydig cells, seminal vesicles and epididymis.5 This is echoed in the finding that compared to clomiphene, enclomiphene not only induces a more robust gonadotropin release, but is also associated with an improvement in total motile sperm cell counts.3 The choice of whether to use Test Booster or enclomiphene would also factor in patient preference.
Q. Other than tracking sex steroid hormones and related biomarkers such as SHBG, is it necessary to monitor any other labs with enclomiphene?
A. As enclomiphene supports endogenous testosterone production rather than introducing exogenous testosterone, changes in serum PSA, lipid levels, and hematocrit may depend on individual patient risk factors. Monitoring decisions should be guided by the patient’s overall clinical context.
Q. My estrogen labs have risen in addition to my testosterone on this med. Should I be concerned?
A. A modest increase in estrogens along with testosterone is nothing to be concerned about. As part of normal physiology, your body will covert some testosterone to estrogen. Enclomiphene generally induces the fewest estrogenic side effects amongst SERMs. It is a misconception that estrogen and testosterone necessarily antagonize each other. When testosterone and estrogen increase in tandem, it may amplify an array of anabolic and libido effects. By itself, estrogen has a weak anabolic effect. But it does play a role in muscle regulation, sensitizing it to exercise stimuli and testosterone’s actions. The increase in estrogen may also have cardioprotective and neuroprotective effects, support bone mineral density and body composition, and contribute to mood and cognitive function.6,7
