Clomifene

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Clomifene , also known as clomiphene , is a drug used to treat infertility in women who do not ovulate. These include those with polycystic ovary syndrome. Use results in greater opportunities than twins. Taken once a day.

Common side effects include pelvic pain and flushes. Other side effects may include changes in vision, vomiting, difficulty sleeping, ovarian cancer, and seizures. This is not recommended in people with liver disease or who are pregnant. Clomifene is in the selective receptor modulator family (SERM) drug. It works by causing GnRH release by the hypothalamus, and then gonadotropin from the anterior pituitary.

Clomifene was approved for medical use in the United States in 1967. This is a List of Essential Medicines of the World Health Organization, the most effective and safe medicines needed in the health system. It is available as a generic drug. Wholesale costs in developing countries are around.79 to 2.00 USD for treatment. In the United States the wholesale cost of treatment treatment is 4.80 USD. The introduction started the era of assisted reproductive technologies.

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Medical use

Clomifene is useful for those who are infertile due to anovulation or oligoovulation. Less evidence for clomifene use in those who are infertile for no known reason. In such cases, studies have observed a clinical pregnancy rate of 5.6% per cycle with clomifene treatment vs 1.3% -4.2% per cycle without treatment.

Clomifene has also been used with other assisted reproductive technologies to improve the success rate of these other modalities.

The exact time of the drug is important; it must be taken starting around the fifth day of the cycle, and there should be frequent sexual intercourse.

The following procedure can be used to monitor the induced cycle:

• Monitoring of the follicle by vaginal ultrasonography, commencing 4-6 days after the last pill. Transvaginal serial ultrasonography can reveal the size and number of developing follicles. It may also provide evidence of ovulation suspicion such as sudden collapse of the preovulatory follicle, and increased volume of fluid in the rectouterine pouch. After ovulation, it can reveal signs of luteinization such as the loss of clear follicular lines and the appearance of internal echoes.
• Serum estradiol levels, starting 4-6 days after the last pill
• Post-coital test 1-3 days before ovulation to check whether there are at least 5 progressive sperm per HPF
• Adequacy of LH surge by urine LH surge test 3 to 4 days after last clomiph pill
• Mid-luteal progesterone, with at least 10 ng/ml 7-9 days after ovulation is considered adequate.

Repeat dose: This 5-day course of treatment can be repeated every 30 days. The dosage can be increased by 50 mg in stages in the next cycle until ovulation is achieved. Not recommended by manufacturers to use clomifene for more than 6 cycles.

It is not recommended to perform an ultrasound examination to rule out significant residual ovarian enlargement before each new treatment cycle.

Clomifene is sometimes used in the treatment of male hypogonadism as an alternative to testosterone replacement therapy. It has been found to increase testosterone levels by 2- to 2.5-fold in hypogonadal men.

Clomifene has been used in the treatment of gynecomastia. It has been found to be useful in the treatment of some cases of gynecomastia but not as effective as tamoxifen or raloxifene for this indication.

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Bad events

The most common adverse drug reaction associated with the use of clomifene (& gt; 10% of people) is reversible ovarian enlargement.

Less common effects (1-10% of people) include visual symptoms (blurred vision, double vision, floaters, eye sensitivity to light, scotomata), headache, vasomotor flushes (or hot flashes), light sensitivity and pupil constriction, abnormal uterine bleeding and/or abdominal discomfort.

Rare adverse events (& lt; 1% of people) include: high blood triglyceride levels, liver inflammation, reversible baldness and/or ovarian hyperstimulation syndrome.

Clomifene may cause some ovulation, thus increasing the likelihood of twins (10% of births, not ~ 1% in the general population) and triplets.

Some studies suggest that clomiphene citrate if used for more than a year may increase the risk of ovarian cancer. This may only happen to those who have never been and do not become pregnant. Subsequent research failed to corroborate these findings. But this is debatable and some feel no significant increase in risk.

The incidence of fetal and neonatal abnormalities for patients on clomifene for fertility is similar to that seen in the general population. There is no data to suggest a higher level of congenital anomaly or spontaneous abortion after taking this drug.

Compared to letrozole, another drug used for ovarian stimulation, a study found no significant differences in overall rates of abnormality, but found that congenital heart abnormalities were significantly higher in the clomifene group than in the letrozole group.

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Pharmacology

Clomifene is a nonsteroidal SERM that inhibits estrogen receptors in the hypothalamus, inhibiting estrogen negative feedback on gonadotropin release, leading to increased regulation of the hypothalamus-pituitary-gonad axis. Zuclomifene, a more active isomer, remains bonded for longer periods of time.

In the hormonal cycle of normal physiologic women, at 7 days of ovulation, the high estrogen and progesterone levels resulting from the corpus luteum inhibit GnRH, FSH and LH in the hypothalamus and anterior pituitary. If fertilization does not occur in the post-ovulatory period, the corpus luteum will be destroyed due to a beta-hCG deficiency. This is usually produced by the embryo in an effort to maintain progesterone and estrogen levels during pregnancy.

In therapy, clomifene is given early in the menstrual cycle. It usually starts from day three and continues for 5 days. At that time, the FSH level increased steadily, leading to the development of multiple follicles. The follicles in turn produce estrogen, which circulates in serum. In the presence of clomifene, the body feels low estrogen levels, similar to 22 days in the previous cycle. Since estrogens can no longer effectively provide negative feedback on the hypothalamus, GnRH secretion becomes faster pulsatil, resulting in increased pituitary release of gonadotropin (FSH, LH). (Faster, lower GNRH pulse amplitude causes increased LH/FSH secretion, while more irregular, larger amplitude pulses than GnRH leads to a decrease in LH/FSH ratio.) Increased FSH levels lead to more growth of ovarian follicles, and subsequent rupture follicles resulting in ovulation. Ovulation occurs most often 6-7 days after clomifene administration.

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Pharmacokinetics

Clomifene produces N-desmethylclomifene, clomifenoxide (clomifene N-oxide), and 4-hydroxyclomifene as a metabolite.

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Chemistry

Clomifene is a triphenylethylene derivative. It is a mixture of two geometric isomers, enclomifene ( (E) -clomifene) and zuclomifene ( (Z) -clomifene). Both of these isomers have been found to contribute to the estrogenic and antiestrogenic properties of the mixture of clomifene.

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History

A team at William S. Merrell Chemical Company led by Frank Palopoli synthesized clomifene in 1956; after his biological activity was confirmed the patent was filed and issued in November 1959. Scientists at Merrell had previously synthesized chlorotrianisene and ethamoxytriphetol.

Clinical studies were conducted under the New Drug Investigation Application; it is the third drug that IND has submitted under the 1962 Kefauver Harris Amendment to the Federal Food, Drug, and Cosmetic Act that has been ratified in response to the thalidomide tragedy. It was approved for marketing in 1967 under the brand name Clomid. It was first used to treat an oligomenorrhea case but was expanded to include anovulatory treatment when the woman undergoing treatment had a higher than expected pregnancy rate.

This drug is widely considered to have been a revolution in the treatment of female infertility, the beginning of the modern era of assisted reproductive technology, and the beginning of what in the words of Eli Y. Adashi, is "the beginning of a US multiple birth of the epidemic".

The company was acquired by Dow Chemical in 1980, and in 1989 Dow Chemical acquired 67 percent of Marion Laboratories shares, renamed Marion Merrell Dow. In 1995, Hoechst AG acquired Marion Merrell Dow's pharmaceutical business. Hoechst in turn became part of Aventis in 1999, and later became part of Sanofi. It becomes the most widely prescribed drug for ovulation induction to reverse anovulation or oligoovulation.

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Society and culture

Rule

Clomifene is on the World Anti-Doping Agency list of illegal doping agents in sports.

Brand name

Clomifene dipasarkan di bawah banyak nama merek di seluruh dunia, termasuk Beclom, Bemot, Biogen, Blesifen, Chloramiphene, Clomen, ClomHEXAL, Clomi, Clomid, Clomidac, Clomifen, Clomifencitrat, Clomifene, ClomifÃÆ'¨ne, Clomifene citrate, Clomifeni citras, Clomifeno, Clomifert, Clomihexal, Clomiphen, Clomiphene, Clomiphene Citrate, Cloninn, Clostilbegyt, Clovertil, Clovul, Dipthen, Dufine, Duinum, Fensipros, Fertab, Fertec, Fertex, Ferticlo, Fertil, Fertilan, Fertilphen, Fertin, Fertomid, Ferton, Fertotab, Fertil , Fetrop, Folistim, Genoclom, Genozym, Hete, I-Clom, Ikaclomin, Klofit, Klomen, Klomifen, Lomifen, MER 41, Milophene, Ofertil, Omifin, Ova-mit, Ovamit, Ovinum, Ovipreg, Ovofar, Ovuclon, Ovulet, Pergotime, Pinfetil, Profertil, Prolifen, Provula, Reomen, Serofene, Serophene, Serpafar, Serpafar, Surole, Tocofeno, dan Zimaquin.

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Riset

Clomifene is studied for the treatment and prevention of breast cancer, but problems with toxicity lead to the neglect of this indication, as is the discovery of tamoxifen. Like structurally structurally related triparanol drugs, clomiphers are known to inhibit the enzyme 24-dehydrocholesterol reductase and increase circulating desmosterol levels, making it unfavorable for long-term use in breast cancer because of the risk of side effects such as irreversible cataracts.

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See also

• Chlorotrianisene
• Tamoxifen
• Ethamoxytriphetol
• Broparestrol
• Triparanol

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References

Source of the article : Wikipedia