Clomphene citrate - True statement is aEUR'
Enclomiphene is anti-estrogenic Clotnifene is structurally related to stilbestrol, It is a weak estrogen agonist having less activity than natural estrogens, so that its ocupation of receptors results in antagonism. Clomiphene acts as an antiestrogen. It has two isomers Zuclomiphene (cis clomiphene) Weak estrogen agonist - Enclomiphene (trans clomiphene) Potent antagonist of estrogen. Clomiphene binds to both the estrogen receptors ccand 13 It acts as pure estrogen antagonist in all human tissues. Antagonists of estrogen receptor are used to induce gonadotropin release in anovulatory feility. Normally estrogen exes negative feedback on the production of LH and FSH. - This .feedback effect seems to operate mainly on the anterior pituitary gland directly but they also operate on the hypothalamus to decrease secretion of GnRh. - Clomiphene blocks hypothalamic estrogen receptors so that the negative feedback of natural estrogens is prevented and the pituitary responds by increased secretion of gonadotropin. In response to increased LH/FSH, ovaries enlarge and ovulation occurs. This is the basis for clomiphene's major pharmacological use? To induce ovulation in women with a functional hypothalamic-hypophyseal ovarian system and adequate endogenous estrogen production. Clinical use of Clomiphene Treatment of disorders of ovulation. Usually a single ovulation is induced by a single course of therapy, and the patient must be treated repeatedly untily the pregnancy is achieved, since normal ovulatory function does not usually resume. The drug is of no value in patients with ovarian or pitutary failure. Oligospermia -- Clomiphene increases gonadotropin secretion in men also and promotes spermatogenesis. Thus it is prescribed even for male infeility. Adverse effects Hot flushes due to estrogen blocks. Polycystic ovaries Multiple pregnancy (incidence is 6-10%), Increased risk of ovarian tumor. The answer is still not clear. Let see each option one by one. Option 'a' (i.e.,Enclomiphene is anti-estrogenic) There is no doubt regarding this one. - Enclomiphene is an anti-estrogen. Option 'lb' (i.e.,Pregnancy rate is 3 times as compared to placebo) From whatever 1 have gathered, this option seems true. The odd ratio for pregnancy in clomiphene citrates is 3.4 when compared to placebo. Here are some excerpts from medical journals "A recent metaanalysis of four randomized placebo controlled studies state that clomiphene showed odds ratio for ovulation- 6.82 and for pregnancy- 3.42 as compared to placebo." "Approximately 75-80% of patients with PCOS will ovulate after clomiphene citrate (Homburg, 2005; Messinis, 2005). Although there appears to he discrepancy between ovulation and pregnancy rates, life-table analysis of the largest and most reliable studies indicates a conception rate of up to 22% per cycle in those ovulating on clomiphene citrate (Hammond et al., 1983; Kousta et al., 1997,- Etikemans et al., 2003)". "The estimate for pregnancy per cycle with clomiphene versus no treatment for oligo-ovulation, is 3.4 (95% CI 1.23, 9.48) (Hughes et al., 1997)". Option `d' (i.e.,it has been shown to increase ,feility in oligospermic males in randomized controlled trials.) Clontiphette citrate is commonly prescribed in male infeility to treat oligospermia, Despite its common use, its efficacy has not been firmly established. There have been several clinical trials confirming the efficacy of clomiphene in oligospermia. But the largest randomized controlled trial undeaken by WHO in 19.92 failed to demonstrate the efficacy of clomiphene in oligospermia. However, most of the subsequent trials though smaller in size, established the beneficial role of clomiphene in oligospennia. An aicle from www.medscape.com states; Antiestrogens in male infeility (clomiphene) "The logic underlying the use of antiestrogens lies in their ability to orably alter the intrinsic HPG honnone axis. The most popular of these drugs is clomiphene citrate, a selective estrogen receptor modulator. By reducing hypothalamic and pituitary sensitivity to estrogens, antiestrogens increase pituitary output of LH and FSH, thus stimulating both testosterone production and spennatogenesis. Despite at least 20 clinical trials with clomiphene citrate for male infeility in the last 30 years, there is still debate about the value of antiestrogens for male infeility. A WHO study of 190 couples found clomiphene to have no significant effect on pregnancy rates or semen characteristics, while an older Cochrane meta-analysis of ten controlled studies involving 738 men showed beneficial hormonal effects, but no effect on pregnancy rates. However, there is emerging literature to suggest that clomiphene citrate may play an impoant role in a subgroup of infeile patients to overcome acquired hypogonadotropic hypogonadism at the pituitary level due to prolactinoma, sickle cell disease, diabetes mellitus and thalassetnias. Other selective estrogen receptor modulator drugs, including tamoxifen citrate, act in a similar fashion to clomiphene citrate". Option 'c' (i.e.,Incidence of twins is 5-6%) The incidence of twin pregnancy mentioned in the option is not far off from the actual incidence. "The incidence of twin pregnancy with clomiphene ranges from minimum 6% to maximum 10%". Still, we can consider this one incorrect.
Enclomiphene is anti-estrogenic
Increases pregnancy rate 3 times as compared to placebo
Incidence of twin pregnancy is 5-6%
It has been shown to increase feility in oligospermic males in randomized controlled trials