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Clomid Review Article

 

Family - everyone dreams of having a familyClomid (Clomifene, Clomiphene, Serophene, Milophene) refers to a group of medicines called anti-estrogens. Drugs in this group specifically bind to estrogen receptors in the hypothalamus and the ovaries. In small doses, the drug enhances the secretion of gonadotropins and stimulates ovulation. At a low content of endogenous estrogens in the body, these drug has a mild estrogenic effect, but at high levels of estrogen, it has an antiestrogenic effect. In large doses this drug can inhibit the secretion of gonadotropins. In connection with abovementioned properties in appropriate doses Clomid is used as a means of stimulating ovulation in anovulatory ovarian dysfunction and associated with it infertility in women. It is also applied for treatment of breast cancer. Due to the fact that Clomid is able of stimulation of gonadotropin secretion the drug is also used for treatment of androgen deficiency, oligospermia in men and delay of sexual and physical development of adolescent males.

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Clomid

Clomid (Clomiphene) is a drug belonging to the group of selective estrogen receptor modulators or SERMs. It is the most commonly prescribed drug for inducing ovulation in infertile females. Its molecular formula is C26H28ClNO and its structural formula is

Fig. 2:Clomiphene Structure
SERMs act on different estrogen receptors found in the cells in different body parts such as breasts, bones, hypothalamus. This action may have different effects: agonist, antagonist or mixed agonist-antagaonist.

In the normal physiological menstrual cycle, high levels of estrogen in day 21 inhibits the gonadotrophin luteinizing hormone (LH) and the follicle stimulation hormone (FSH). These two hormones are important for ovulation, because they induce the growth of ovarian follicles. Inhibition of this hormones prevents ovulation. Clomid acts by antagonizing estrogen in the hypothalamus, inhibiting its negative feedback mechanism on the gonadotrophin. This results to an increase on these two hormones, inducing ovulation.

Clomid is taken orally in the beginning, day three or day five (ask your physician) of the menstrual cycle. It is taken once a day for five days at exact 24 hours intervals (PubMed). Most females do not need treatment for more than six months because of the positive results obtained.
Fig.3 The Menstrual Cycle
Clomid Effectiveness

The effectiveness of Clomid has long been established. In 1961, Asch & Greenblatt first proposed Clomiphene Citrate as a drug to induce ovulation. Fifiteen years later, the same researchers found that the benefits of using the drugs outweighs its side effects. Side effects include flushing, upset stomach, vomiting, breast discomfort, vaginal bleeding, blurry vision, and multiple births. In 1977, Garcia, Jones & Wentz found as well that clomiphene citrate is effective in treating anovulatory females.

The American Society of Reproductive Medicine states that the success rate for this drug is good with 80% of women having ovulation in the first treatment cycle. Chance of conception in the first month is 30%, a 5% increase from a normal couple’s chance of conception.

Clinical and laboratory study was done by Lobo et al. in 1982 to determine possible factors that may affect clomiphene response in females. Body weight and obesity were found to have a positive correlation to clomiphene response. Another study of Dickey et al. (1997) found the same relationship between weight and Clomid dosage.

Asch and Greenblatt also found that Clomid may be used as an aid in diagnosing infertility. This method of diagnosis was called Clomiphene Citrate challenge and it was later proven to be effective by Scott et al. (1993).

Male Infertility

Many people think that clomiphene citrate is an effective drug for infertility - both for male and females. But several studies have shown that this is just a myth. Male infertility can not be treated with clomiphene. In a study of Sokol et al (1988), clomiphene was compared to a placebo. They found that there were no significant differences and therefore the ineffectiveness of clomiphene in male infertility. Another study conducted by the World Health Organization found similar results.

Polycystic Syndrome

Polycystic Ovary Syndrome (PCOS) is a medical condition where there is a hormonal imbalance of female sex hormones. The exact cause of this condition is unknown but this hormone imbalance contributes to fertility (PubMed Health). Clomid is used in this condition together with other drugs such as metformin. Legro et al. (2007) found that Clomid is superior to Metformin in treating PCOS. It was also found that the combination of the two drugs is more effective.

Multiple Births

Several studies have proven that multiple birth is a side effect of Clomid. It was found that there is a 6.9% of having twins, 0.5% triplets, 0,3% quadruplets and 0.1% quintuplets. In a study by Levene, Wild and Steer, it was discovered that assisted ovulation (with clomiphene or other gonadotrophins) accounted for all quadruplet and quintuplet conceptions. Studies recommend the use Clomid therapy should start at the lowest possible dose to counteract this side effect.

Bibliography

AMERICAN SOCIETY FOR REPORDUCTIVE MEDICINE. Medications for inducing ovulation: A guide for patients. Retrieved from
http://infertility.about.com/gi/o.htm?zi=1/XJ&zTi=1&sdn=infertility&cdn=health&tm=37&f=10&tt=12&bt=1&bts=1&zu=http%3A//asrm.org/uploadedFiles/ASRM_Content/Resources/Patient_Resources/Fact_Sheets_and_Info_Booklets/ovulation_drugs.pdf

ASCH, R.H. & GREENBLATT, R.B. 1976. Update on the safety and efficacy of clomiphene citrate as a therapeutic agent. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/787524

DICKEY, R.P., TAYLOR, S.N., CUROLE, et.al. 1997. Relationship of clomiphene dose and patient weight to successful treatment. Retrieved from http://humrep.oxfordjournals.org/content/12/3/449.short

GARCIA, J., JONES, G.S., & WENTZ, A.C. 1977. The use of clomiphene citrate. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/872951

LEGRO, R.S., BARNHART, H.X., SCHLAFF, W.D., et.al. 2007. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMoa063971

LEVENE, M.I., WILD, J., & STEER, P. 2005. Higher multiple births and the modern management of infertility in Britain. Retrieved from http://onlinelibrary.wiley.com/doi/10.1111/j.1471-0528.1992.tb13831.x/full

LOBO, R.A., GYSLER, M., MARCH, C.M., GOEBELSMANN, U., & MISHELL, D.R. Jr. 1982. Clinical and laboratory predictors of clomiphene response. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/7199484

MERCK MANUAL. Overview of infertility. Retrieved from http://www.merckmanuals.com/home/sec22/ch251/ch251a.html

PUBMED HEALTH. Clomiphene. Retrieved from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000752/

SOKOL, R.Z., STEINER, B.S., BUSTILLO, M., PETERSEN, G., & SWERDLOFF, R.S. 1988. A controlled comparison of the efficacy of clomiphene citrate in male infertility. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/3129318/

WORLD HEALTH ORGANIZATION. Infertility. Retrieved from http://www.who.int/topics/infertility/en/

WORLD HEALTH ORGANIZATION. 1992. A double-blind trial of clomiphene citrate for the treatment of idiopathic male infertility. Retrieved from http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2605.1992.tb01129.x/abstract


 

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