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Reproductive Physiology, Endocrinology, and Infertility

Question
39 out of 56
 

Clomphene citrate – true statement is (AIIMS May 2011)



A Enclomiphene is anti-estrogenic

B Increases plregnancy rate 3 times as compared to placebo

C Incidence of twin pregnancy is 5-06 %

D It has been shown to increase fertility in oligospermic males in randomized controlled trials

Ans. A

Enclomiphene is anti-estrogenic

1. It is a racemic mixture of enclomiphene and zuclomiphene.
Enclomiphene is a more potent isomer responsible for its ovulation-inducing action.

2. It is a selective estrogen receptor modulator (SERM) that increases production of gonadotropins by inhibiting negative feedback on the hypothalamus.

3. In normal physiologic female hormonal cycling, at 7 days past ovulation, high levels of estrogen and progesterone produced from the corpus luteum inhibit GnRH, FSH and LH at the hypothalamus and anterior pituitary. If fertilization does not occur in the post-ovulation period the corpus luteum disintegrates due to a lack of beta-hcg. This would normally be produced by the embryo in the effort of maintaining progesterone and estrogen levels during pregnancy.

4. Therapeutically, clomifene is given early in the menstrual cycle. It is typically prescribed beginning on day 1, 3 or 5 and continuing for 5 days. By that time, FSH level is rising steadily, causing development of a few follicles. Follicles in turn produce the estrogen, which circulates in serum. Clomifene acts by inhibiting the action of estrogen on the pituitary. This prevents normal receptor recycling and causes an effective reduction in hypothalamic estrogen receptor number. As a result, the body perceives a low level of estrogen, similar to day 22 in the previous cycle. Since estrogen can no longer effectively exert negative feedback on the hypothalamus, GnRH secretion becomes more rapidly pulsatile, which results in increased pituitary gonadotropin (FSH, LH) release.

5. Common adverse drug reactions associated with the use of clomifene (≥1% of patients) include: vasomotor flushes (or hot flashes), abdominal discomfort, visual blurring (dose-dependent), and/or reversible ovarian enlargement and cyst formation. Infrequent adverse effects (0.1–1% of patients) include: abnormal uterine bleeding, nausea, and/or vomiting. Rare adverse effects (<0.1% of patients) include: reversible alopecia and/or ovarian hyperstimulation syndrome.

6. Clomifene can lead to multiple ovulation, hence increasing the chance of twins (10% of births instead of the normal ~1%). In comparison to treatment with purified FSH, the rate of ovarian hyperstimulation syndrome is low. There may be an increased risk of ovarian cancer and weight gain.

7. It has NOT been shown to increase fertility in oligospermic males in randomized controlled trials.

Reproductive Physiology, Endocrinology, and Infertility Flashcard List

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