Clomid vs enclomiphene is a common comparison because the two are closely related. Clomid (clomiphene citrate) is actually a mixture of two forms of the same molecule, and enclomiphene is one of them. Both can raise testosterone in men by changing the body’s hormonal signals, but they differ in how they act, in their approval status, and in how much research supports them.
This article explains what each drug is, how they differ, how they affect testosterone, their side effects, and their regulatory status.
What is Clomid?
Clomid is a brand name for clomiphene citrate, a selective estrogen receptor modulator (SERM). It is approved in the United States to induce ovulation in women with certain types of ovulatory dysfunction.
Clomiphene is a mixture of two isomers, mirror-image forms of the same molecule: enclomiphene, which makes up roughly 60% of the mixture, and zuclomiphene, which makes up the rest. The two isomers behave quite differently in the body.
Doctors sometimes prescribe clomiphene off-label for men with certain types of low testosterone, particularly when low testosterone is caused by reduced signaling from the brain rather than by the testes themselves, and when preserving fertility is a priority.
What is enclomiphene?
Enclomiphene is the trans-isomer of clomiphene, separated from the mixture. It was developed as a potential treatment for secondary hypogonadism in men, low testosterone caused by insufficient signaling from the pituitary gland.
In clinical trials in men with this condition, enclomiphene raised testosterone levels while preserving sperm counts. In contrast, topical testosterone raised testosterone but lowered sperm counts (Kim et al., 2016).
Despite these trials, enclomiphene has never been approved by the US Food and Drug Administration (FDA).
How do clomiphene and enclomiphene differ?
The role of zuclomiphene
The main difference between the two lies in zuclomiphene, the isomer present in clomiphene but not in enclomiphene. Enclomiphene acts mainly as an estrogen blocker, while zuclomiphene has more estrogen-like activity. Zuclomiphene is also cleared from the body much more slowly, so it can build up over time with continued use.
Because of this, enclomiphene has been proposed as a more targeted option for raising testosterone, without the estrogen-like effects of zuclomiphene.
Strength of the evidence
Clomiphene has been used for decades and has a long record of use, although its use in men is off-label. Enclomiphene has been studied in a smaller number of clinical trials of limited duration. Claims that enclomiphene causes fewer side effects than clomiphene are plausible, but they are not yet supported by large, long-term comparative studies.
How do they affect testosterone?
In men, estrogen is part of the feedback system that controls testosterone production. It signals to the hypothalamus and pituitary gland that hormone levels are sufficient, reducing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
Clomiphene and enclomiphene block estrogen receptors in the brain, so the brain senses less estrogen and increases LH and FSH. This stimulates the testes to produce more testosterone and supports sperm production. This differs from testosterone therapy, which supplies testosterone directly and suppresses the body’s own production and sperm output.
This mechanism is why both drugs are discussed in the context of recovering natural testosterone after anabolic steroid use. However, using them for that purpose is not an approved indication, and recovery after steroid use varies widely, as explained in our article on testosterone recovery after steroids. Our article on steroids and male fertility explains how steroid use affects sperm production.
What are the side effects?
Clomiphene
Reported side effects of clomiphene include hot flashes, mood changes, headache, and breast tenderness. It can also cause visual disturbances, such as blurred vision or seeing spots or flashes. These are uncommon, but anyone who experiences vision changes while taking clomiphene should stop and contact their doctor.
Enclomiphene
In clinical trials, enclomiphene was generally well tolerated, with side effects such as headache reported. Because the trials were relatively small and short, its long-term safety is not well established.
How do they compare with Nolvadex and Arimidex?
Clomiphene and enclomiphene belong to the same broad drug class as tamoxifen (Nolvadex), since all are SERMs. Anastrozole (Arimidex) works differently, by lowering estrogen production rather than blocking its receptors. Our article on Nolvadex vs Arimidex explains these differences.
Are clomiphene and enclomiphene regulated?
Clomiphene is an FDA-approved prescription medication. Enclomiphene has no FDA-approved product in the United States. It is available only through compounding pharmacies with a prescription, and compounded drugs are not reviewed by the FDA for safety, effectiveness, or quality.
Enclomiphene’s compounding status is under review. It is listed in the FDA’s Category 1 of bulk drug substances under evaluation, which compounding pharmacies may use while the review is pending (FDA, 2026). In 2022, an FDA advisory committee voted against adding it to the list of substances permanently approved for compounding, although the FDA has not yet made a final decision.
In competitive sport, SERMs, including clomiphene and enclomiphene, are prohibited at all times under the World Anti-Doping Agency (WADA) Prohibited List (WADA, 2026).
When to speak with a doctor
Symptoms of low testosterone, such as low sex drive, fatigue, and low mood, can have many causes. A doctor can test hormone levels, identify the type and cause of low testosterone, and discuss appropriate treatment, including options that protect fertility if that is a priority. Anyone taking clomiphene or enclomiphene should do so under medical supervision.
The bottom line
The difference between Clomid vs enclomiphene comes down to composition. Clomid is a mixture of two isomers, enclomiphene and zuclomiphene, while enclomiphene is one isomer on its own, without zuclomiphene’s estrogen-like activity and slow clearance. Both can raise testosterone in men by increasing LH and FSH, which also supports sperm production.
Clomiphene is FDA-approved for ovulation induction in women and used off-label in men, while enclomiphene has never been FDA-approved and is available only through compounding. Evidence that enclomiphene causes fewer side effects is still limited. Anyone considering either should speak with a qualified healthcare professional.
References
Food and Drug Administration. Bulk drug substances nominated for use in compounding under section 503A of the FD&C Act. List updated May 14, 2026.
Kim ED, McCullough A, Kaminetsky J. Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: two parallel randomized phase II clinical trials. BJU International. 2016;117(4):677–685. World Anti-Doping Agency. The 2026 Prohibited List. World Anti-Doping Code International Standard.
