Case 3

3. What is clomiphene? What is its mechanism of action, clinical use, adverse effects and
contraindications?

Clomiphene:

 A triphenyl ethylene stilbene derivative which is an estrogen agonist or antagonist depending on

the target tissue.
 Clomiphene is an ovulatory stimulant. It is used to induce ovulation in women who do not
produce ova but wish to become pregnant. It works similarly to estrogen, a female hormone
that causes eggs to develop in the ovaries and be released.

Mechanism of Action:

 Clomiphene has both estrogenic and anti-estrogenic properties, but its precise mechanism of
action has not been determined. Clomiphene appears to stimulate the release of gonadotropins,
follicle-stimulating hormone (FSH), and luteinizing hormone (LH), which leads to the
development and maturation of ovarian follicle, ovulation, and subsequent development and
function of the corpus luteum, thus resulting in pregnancy. Gonadotropin release may result
from direct stimulation of the hypothalamic-pituitary axis or from a decreased inhibitory
influence of estrogens on the hypothalamic-pituitary axis by competing with the endogenous
estrogens of the uterus, pituitary, or hypothalamus. Clomiphene has no apparent
progestational, androgenic, or antrandrogenic effects and does not appear to interfere with
pituitary-adrenal or pituitary-thyroid function.

Clinical Use:

 Used mainly in female infertility due to anovulation (e.g. due to polycystic ovary syndrome) to
induce ovulation.
 Clomiphene is also sometimes used to treat male infertility, menstrual abnormalities, fibrocystic
breasts, and persistent breast milk production. Talk to your doctor about the possible risks of
using this medication for your condition.

Adverse Effects:

 Ovarian enlargement
 abdominal or pelvic discomfort including distention, bloating, or pain
 hot flushes

Contraindications:

 Pregnancy (Category X)
 Liver disease or history of liver dysfunction
 Abnormal uterine bleeding of undetermined origin
 Ovarian cysts or enlargement (unless due to polycystic ovarian syndrome)
 Uncontrolled thyroid or adrenal dysfunction
  Presence of an organic intracranial lesion (e.g., pituitary tumor)
 Known hypersensitivity to clomiphene or any ingredient in the formulation
References:

Clomid, Serophene (clomiphene) dosing, indications, interactions, adverse effects, and more. (2018,
March 11). Retrieved from https://reference.medscape.com/drug/clomid-serophene-clomiphene-
342752

Clomifene. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB00882

Clomiphene Citrate Monograph for Professionals. (n.d.). Retrieved from

https://www.drugs.com/monograph/clomiphene-citrate.html

Clomiphene: MedlinePlus Drug Information. (n.d.). Retrieved from

https://medlineplus.gov/druginfo/meds/a682704.html