What are the indications for Clomiphene (Clomid)?

From the Guidelines

Clomiphene is primarily indicated for the treatment of infertility in women with ovulatory dysfunction, particularly those with polycystic ovary syndrome (PCOS), as well as unexplained infertility and mild endometriosis-related infertility. The standard regimen involves 50mg taken orally once daily for 5 days, typically starting on day 3-5 of the menstrual cycle 1. If ovulation doesn't occur, the dose may be increased to 100mg daily for 5 days in subsequent cycles, with a maximum of 150mg daily. Treatment is usually limited to 3-6 cycles due to diminishing returns and potential risks with prolonged use. Clomiphene works as a selective estrogen receptor modulator (SERM) that blocks estrogen receptors in the hypothalamus, reducing negative feedback and increasing gonadotropin release, which stimulates ovarian follicle development.

Some key points to consider when using clomiphene include:

• The risk of multiple pregnancies, which can be mitigated by careful monitoring with ultrasound to track follicular development and timing of ovulation 1
• The potential for ovarian hyperstimulation syndrome (OHSS), particularly when used in conjunction with other fertility treatments 1
• The importance of individualizing treatment and adjusting doses as needed to minimize risks and maximize efficacy 1
• The potential off-label use of clomiphene in men with hypogonadism to increase testosterone levels, although this is not a primary indication 1

It's also important to note that clomiphene may not be effective in all cases, particularly in women with functional hypothalamic amenorrhea (FHA), where the use of clomiphene is not recommended as first-line treatment due to uncertain chances of success 1. Ultimately, the decision to use clomiphene should be made on a case-by-case basis, taking into account the individual patient's needs and medical history. The most recent and highest quality evidence supports the use of clomiphene as a first-line treatment for infertility in women with PCOS and other ovulatory disorders 1.

From the FDA Drug Label

Clomiphene citrate is indicated for the treatment of ovulatory dysfunction in women desiring pregnancy. Those patients most likely to achieve success with clomiphene therapy include patients with polycystic ovary syndrome, amenorrhea-galactorrhea syndrome, psychogenic amenorrhea, post-oral-contraceptive amenorrhea, and certain cases of secondary amenorrhea of undetermined etiology.

The indications for clomiphene are:

• Ovulatory dysfunction in women desiring pregnancy
• Specific conditions that may benefit from clomiphene therapy include:
  • Polycystic ovary syndrome
  • Amenorrhea-galactorrhea syndrome
  • Psychogenic amenorrhea
  • Post-oral-contraceptive amenorrhea
  • Certain cases of secondary amenorrhea of undetermined etiology 2

From the Research

Indications for Clomiphene

• Clomiphene citrate is indicated for ovulation induction in patients with polycystic ovary syndrome (PCOS) associated with infertility owing to anovulation 3
• It is accepted as the first-line method for ovulation induction (OI) in patients with PCOS 3
• Clomiphene citrate should be the first-line treatment for ovulation induction in anovulatory patients with PCOS 4
• It is used for the treatment of infertile women with PCOS-related anovulation, without prior ovulation induction treatment 3

Comparison with Other Treatments

• Letrozole is a better alternative for ovulation induction in anovulatory women with PCOS as pregnancy rates are higher, time to pregnancy is shorter, and chances of multiple pregnancy are less because of high monofollicular growth 5
• Gonadotropins (FSH) probably result in more live births than continued clomiphene citrate in women with PCOS who do not ovulate or conceive on clomiphene citrate or letrozole 6
• Clomiphene citrate is more effective than metformin for ovulation induction and pregnancy achievement in Asian women with PCOS 4

Special Considerations

• Aromatase inhibitors, such as letrozole and anastrozole, may have ovulation-inducing effects and can be considered in a subset of women with PCOS and infertility, specifically those who are clomiphene citrate resistant or not candidates for clomiphene citrate, gonadotropins, or GnRH analogs 7