Enclomiphene for men on TRT

November 9, 2023

What is enclomiphene used for in males?

Enclomiphene is a medication that is used by both men and women to treat infertility. In women it works by stimulating ovulation and is often prescribed for females who have irregular periods or PCOS, which stands for polycystic ovary syndrome. Men, however, may use Enclomiphene for more than just fertility, as it may help address hypogonadism, which is a condition where the body isn’t producing enough testosterone.

Enclomiphene may work in men by stimulating the production of testosterone in patients, which makes it a potential treatment for low T. Some men take it in conjunction with testosterone as part of their hormone replacement therapy protocol.

What is Enclomiphene?

Enclomiphene citrate is a medication that is the trans isomer Clomiphene Citrate, commonly known as Clomid. It is a non-steroidal estrogen receptor antagonist, which has been approved by the FDA for treating ovarian dysfunction in women. It has also been used off label by physicians for many years in the treatment of secondary male hypogonadism.

"Hypogonadism is a clinical syndrome that results from failure of the testis to produce physiological concentrations of testosterone (T) (T deficiency) and/or a normal number of spermatozoa due to pathology at one or more concentrations of the hypothalamic–pituitary– testicular axis" - The Journal of Clinical Endocrinology & Metabolism
It has been commonly prescribed for men receiving infertility treatment, however, it is now a popular medication being utilized for the purposes of testosterone replacement therapy. This is especially true now due to recent regulatory changes regarding human chorionic gonadotropin, or hCG, which was commonly prescribed for men. As there is an increase in demand and a decrease in availability, the costs of hCG have gone up in the past few years and patients and providers alike are utilizing alternatives such as gonadorelin, kisspeptin, clomid and enclomiphene instead.

HCG is a similar medication, and it helps stimulate both testosterone and sperm production in men and can prevent testicular atrophy for men on TRT who may be experiencing that as a side effect.

What is The Difference Between Clomid and Enclomiphene?

Clomid and enclomiphene are similar medications. Enclomiphene is the active form of Clomid and both have been used to treat low testosterone and men, however, individual responses will differ, and the choice between which medication to use will depend on factors like side effects, patient preferences, medical need, and the recommendation from your healthcare provider. Clomid contains a mixture of two different isomers: 1 is zuclomiphene and the other is enclomiphene. Enclomiphene is the active isomer which is believed to be responsible for the medication's effect on the treatment is infertility and low T. Enclomiphene citrate is a more targeted form of this active isomer and more commonly prescribed by TRT providers. So, while Clomid contains both isomers, enclomiphene itself focuses just on the one beneficial isomer for these specific treatments.

As it turns out, Enclomiphene citrate has been shown to be successful in raising of serum testosterone levels by increasing luteinizing hormone and follicle stimulating hormone levels (LH and FSH) in men. This occurs without negatively impacting the production of semen. This ability to help improve testosterone levels and men with androgen deficiency without the negative impact of fertility, helps to support the role of this medication for its use in treating men when testosterone therapy itself is not necessarily a viable option.

How Does Enclomiphene Work?

In men, Enclomiphene works through the blocking of estrogen, receptors in the brain which will tend to lead to an increase in the production of LH and FSH, which increases production of testosterone in the testes and increase sperm production as well.

Testosterone and estrogen have been traditionally, considered to be both men and women’s sex hormones respectively, however, both hormones play a significant role for both men and women. Estradiol is vital in the regulation of sex drive in men, as well as formation of sperm cells, and erectile functioning. Estrogen, receptors, and aromatase, which is an enzyme that transforms testosterone into estrogen, are found within the brain, testes and penis and are vital for sexual functioning. In a man’s brain, the synthesis of estradiol increases in the regions that are related to sexual arousal. Also, in a man’s penis, the same estrogen, receptors can be located throughout the corpus cavernosum, and are highly concentrated near neurovascular bundles. Elevated levels of estrogen and decreased levels of testosterone will increase the occurrences of ED or erectile dysfunction, independently of one another.

Within the testes, the formation of sperm, otherwise known as spermatogenesis, is highly regulated at every level by Estrogen, starting with the HPG axis (hypothalamus–pituitary–gonadal), this releases, LH and FSH to stimulate the Leydig, Sertoli, and germ cells in the testes. This also regulates cells within the ductal epithelium. After sperm leaves the testes, the sperm passes through the epididymis, ductus deferens, ejaculatory duct, and urethra which are all regulated in part through estrogen.

The regulation of these testicular cells by estradiol, as indicated, both a stimulatory and inhibitory influence, which shows there is a complex relationship between hormone levels within the body. Any medication, such as testosterone, hCG, Clomid, enclomiphene or an aromatase inhibitor, (AI) such as anastrozole, needs to be carefully considered, and monitored by an experienced physician, due to the importance that these hormones play, in balancing such important overall roles in men, such as spermatogenesis, libido and erectile functioning. Any increase or decrease in one hormone will directly influence the others.

What Effect Does Enclomiphene Have on Estrogen Production?

Testosterone can be turned into estrogen through the process called aromatization. Higher testosterone levels often lead to increases in estrogen levels. Maintaining the balance between testosterone and estrogen is vital for the overall hormonal health in both men and women alike. Enclomiphene also blocks the binding of estrogen to estrogen receptors at the hypothalamus and pituitary glad in the brain. Enclomiphene has a shorter half life than clomid and stays in the blood stream for less time making it a viable option for HRTR.

Conversely, high levels of estrogen in men could suppress the production of testosterone. A males body typically maintains a delicate balance between testosterone and estrogen, and an increase of estrogen could potentially have a negative effect on the feedback mechanisms which regulate testosterone production in the testes.

What are the Side Effects of Enclomiphene?

Some of possible side effects from enclomiphene in men could include hot flashes, headaches, and even an increased libido. (An increase in sex drive may or may not be welcome depending on the individual). It’s extremely important to have a consultation with a medical professional or healthcare provider for individual advice, and to not only carefully consider but monitor any of the possible side effects that may occur during treatment. Depending on the patient’s bloodwork, past medical history, tolerance to a medication, they may be prescribed enclomiphene for low T treatment. The typical starting dose for patients prescribed enclomiphene is normally 12.5 to 25 mg a day for men. The exact dosage may vary based on individual factors and needs to be prescribed by a licensed and experienced healthcare provider. It’s vital to monitor and assess the response and make adjustments to the dose as needed.