Clomifene
Clomifene (clomiphene) is a SERM, a mixture of two isomers (enclomiphene and zuclomiphene). Like tamoxifen it blocks oestrogen feedback at the pituitary to raise LH, FSH and testosterone, and it is widely used in PCT and for male hypogonadism/fertility. Its distinctive drawback is oestrogenic-agonist visual side effects — blurring, floaters and flashes — driven largely by the long-lived zuclomiphene isomer.
01 Overview
Clomifene antagonises oestrogen at the hypothalamus and pituitary, increasing gonadotropin release and thereby stimulating testicular testosterone production. This makes it a common PCT agent to restart the HPTA and a prescribed option for secondary hypogonadism in men who wish to preserve fertility.
It is a 50:50 mixture of enclomiphene (a purer antagonist, cleared quickly) and zuclomiphene (a longer-acting oestrogen agonist that accumulates over weeks). The zuclomiphene fraction is responsible for the visual disturbances that are more associated with clomifene than with tamoxifen; these usually reverse on discontinuation but can be a reason to switch agents.
02 Mechanism
SERM that antagonises oestrogen receptors at the hypothalamus/pituitary, reducing negative feedback and raising LH, FSH and endogenous testosterone.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Male hypogonadism/fertility | 12.5–50 mg/day | Oral | Off-label male use, often every other day; titrate to testosterone and tolerance. |
| PCT | 25–50 mg/day | Oral | Typically 25-50 mg/day for 4-6 weeks; sometimes a higher loading dose initially. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Raised testosterone via LH/FSHReliably increases gonadotropins and endogenous testosterone in men with intact testes. | often doubles testosterone | Clinical | |
| Preserved fertilityUnlike exogenous testosterone it stimulates rather than suppresses the testes, supporting spermatogenesis. | improved sperm parameters | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Visual disturbancesBlurred vision, floaters, flashes and light sensitivity, more common at higher doses and with prolonged use. | Moderate | Uncommon but characteristic | Clinical | |
| Mood changes / irritabilityEmotional lability, low mood or anxiety reported by some men on clomifene. | Mild | Common | Observational | |
| Hot flushesVasomotor flushing during use. | Mild | Common | Clinical |