Clomiphene

• Clomiphene binds to oestrogen receptors in the hypothalamus but does not activate them. It therefore blocks the binding of oestradiol and thus prevents negative feedback inhibition of FSH secretion
• the action of clomiphene results in greater stimulation of ovarian follicles via increased FSH
  • when a woman is being treated with clomiphene then ultrasound monitoring should be used to identify whether the woman has produced a dominant follicle, an indicator of likely ovulation. Serum progesterone concentrations can also be used to help confirm ovulation, and also LH concentrations, because clomifene can cause an exaggerated secretion of LH in the mid-follicular phase, an effect associated with a reduced chance of conception (because it changes the consistency of cervical mucus)
• there is an increased incidence of multiple ovulation with the use of clomiphene
• clomiphene must be used with caution in cases of polycystic ovarian syndrome

As regards the number of clomiphene cycles, most patients who are going to respond will do so to first course, 3 courses should constitute adequate therapeutic trial; long-term cyclical therapy not recommended (beyond a total of 6 cycles).

The summary of product characteristics must be consulted before prescribing this drug.

Note - studies have shown letrozole, an aromatase inhibitor, to be the most effective oral agent than clomiphene or the combination of clomiphene and metformin to induce ovulation in patients with polycystic ovarian syndrome. (2)

Reference:

1. NICE. Fertility problems: assessment and treatment. NICE guideline NG257. Published March 2026
2. Rezk M, Shaheen AE, Saif El-Nasr I. Clomiphene citrate combined with metformin versus letrozole for induction of ovulation in clomiphene-resistant polycystic ovary syndrome: a randomized clinical trial. Gynecol Endocrinol. 2018 Apr;34(4):298-300.