Enclomiphene Citrate, Pregnancy, and Lactation: What Is Known, and Not Known

What enclomiphene is

Enclomiphene is the trans isomer of clomiphene citrate and an oral selective estrogen receptor modulator. It blocks estrogen receptors in the pituitary, so more LH and FSH are released and the testes produce more testosterone [1]. Clomiphene citrate is the mixture of enclomiphene and zuclomiphene, with enclomiphene making up 50 to 70 percent under the USP monograph [1]. Clomiphene is FDA-approved for ovulatory dysfunction in women who want to become pregnant [5]. Enclomiphene has no approved indication [1][2].

Pregnancy and breastfeeding: the evidence

The enclomiphene studies cited here enrolled men. The phase 3 programme compared enclomiphene with testosterone gel in overweight men aged 18 to 60 with secondary hypogonadism [3], and the phase 2 trials enrolled men with the same condition [7][4]. EMA's review of EnCyzix covered four main studies in 588 men with hypogonadotropic hypogonadism [6]. Those studies measured testosterone, LH, FSH and sperm counts, not pregnancy outcomes or infant development [3][4].

What is known is how the drug behaves in the body: after an oral dose it peaks at 2 to 3 hours, has a half-life of about 10 hours, and is excreted mainly in feces [1].

What the clomiphene label says, for a different product

The Clomid label says clomiphene use in pregnant women is contraindicated, as it does not offer benefit in that population; it states that available human data do not suggest an increased risk of congenital anomalies above background when used as indicated, while animal reproductive studies showed increased embryo-fetal loss and structural malformations [5]. The same label notes that zuclomiphene has a longer half-life than enclomiphene, with detectable levels persisting longer than a month, and says it is possible that some active drug may remain in the body during early pregnancy in women who conceive during clomiphene therapy [5]. These statements describe the approved mixture. They are not enclomiphene data.

Safety signals and regulatory history

FDA listed cardiac and thromboembolic events, including pulmonary embolism and deep vein thrombosis in a safety study, plus raised estradiol, PSA and hematocrit, and noted that long-term safety data are lacking [1]. EMA's committee adopted a negative opinion in January 2018 recommending refusal of marketing authorisation for EnCyzix, citing venous thromboembolism risk and studies that showed higher testosterone but did not examine whether symptoms improved [6]; FDA's presentation notes that EMA found a slightly higher rate of cardiac and thromboembolic events than with testosterone [1]. A 2026 BSSM position statement says the manufacturer discontinued development in 2021 and that long-term efficacy and safety data are lacking [2].

Why there is no enclomiphene labelling

With no approved product, there is no FDA pregnancy or lactation labelling for enclomiphene, and FDA lists enclomiphene citrate as a bulk substance under evaluation rather than as an approved drug [1][8]. Clomiphene citrate and enclomiphene are related but not the same drug [1].