Clomiphene citrate is an anti-estrogenic drug that is prescribed to women to treat anovulatory infertility (inability to ovulate). In clinical medicine it is specifically referred to as a nonsteroidal ovulatory stimulant. The drug works by interacting with estrogen receptors, often in an antagonistic manner, in various tissues of the body including the hypothalamus, pituitary, ovary, endometrium, vagina, and cervix. One main focus is that the drug will oppose the negative feedback of estrogens on the hypothalamic-pituitary-ovarian axis, enhancing the release of gonadotropins (LH and FSH). This surge in gonadotropins may cause egg release (follicular rupture), ideally leading to conception. Clomiphene citrate is chemically a synthetic estrogen with both agonist/antagonist properties, and in this regard is very similar in structure and action toNolvadex. It is believed that both the estrogenic and anti-estrogenic properties of clomiphene citrate play a role in its ability to support female fertility. In men, clomiphene citrate also acts as a partial anti-estrogen, and may be used to counter some of the side effects of aromatizable steroid use including gynecomastia and increased water retention. As an anti-estrogenic drug, clomiphene citrate may also produce an elevation of follicle stimulating hormone, and luteinizing hormone levels, which can elevate testosterone production. This effect is especially beneficial at the conclusion of a steroid cycle, when endogenous testosterone levels are depressed. Here, clomiphene citrate is most often applied in combination withhCG and tamoxifen, in an effort to restore endogenous testosterone production more quickly (see Post-Cycle Therapy). If testosterone levels are not brought back to normal in a short period of time, a significant loss in size and strength may occur. This is due to the fact that without testosterone (or other anabolic/androgenic steroids) to impart an ongoing anabolic message, the catabolic hormone cortisol becomes the dominant force affecting muscle protein synthesis. Often referred to as the post-steroid crash, when not corrected this state of imbalance in the endocrine system can quickly reduce muscle mass levels, diminishing the long-term return on anabolic/androgenic steroid therapy. Note that the triphenylethylene compounds (toremifene citrate,tamoxifen citrate, clomiphene citrate) tend to be somewhat intrinsically estrogenic in the liver. This means that while they can block estrogenic activity in some areas of the body, they can actually act as estrogens in can block estrogenic activity in some areas of the body, they can actually act as estrogens in this other key area. Estrogenic action in the liver is important in the regulation of serum cholesterol (it tends to support HDL synthesis and LDL reductions). Since steroid-using bodybuilders are already dealing with the negative cardiovascular effects of these drugs, compounding the issue with aromatase inhibitors (which will lower total serum estrogen levels) may not always be the best option. Using a drug that blocks gynecomastia, for example, while at the same time supporting improved cholesterol values, might be much more ideal.
|Brand name||Clomid, Clomiphene citrate, Serofene, Sepafar, Omifin, Pergotime, Gonaphene, Duinum, Clostil, Ova-Mit, Clostibegyt|
Clomiphene Citrate History
Clomiphene citrate is a fertility drug with a substantial history of use in the United States. It first gained widespread acceptance during the early 1970s, and has been a drug common to the fertility practice ever since. The drug is now considered a standard medication for certain forms of fertility therapy, and has been adopted as such far outside U.S. border. Clomiphene citrate is presently available in most nations worldwide. The two most popular brand names one is likely to encounter are Clomid and Serofene, although the drug can be found under numerous other trade names as well including (but not limited to) Sepafar, Omifin, Pergotime, Gonaphene, Duinum, Clostil, Ova-Mit, and Clostibegyt. Clomiphene citrate is generally a very inexpensive medication compared to stronger anti-estrogens such as the newer selective third-generation aromatase inhibitors. It, likewise, remains a very popular agent of use among bodybuilders and athletes.
How is Clomiphene Citrate Supplied
Clomiphene citrate is most commonly supplied in tablets of 50 mg.
Structural Characteristics of Clomiphene Citrate
Clomiphene citrate is classified as a selective estrogen receptor modulator, with both agonist and antagonist properties. It has the chemical designation 2-[4-(2-chloro1,2-diphenylvinyl) phenoxy] triethylamine dihydrogen citrate.
Clomiphene Citrate Warnings (Visual Symptoms)
Some patients using clomiphene citrate notice blurring or other visual disturbances such as spots or flashes. These symptoms occur more frequently at higher doses or longer durations of therapy, and often disappear within a few days or weeks of use. Prolonged visual disturbances have been reported after the discontinuation of clomiphene citrate therapy, however, and in some cases may be irreversible. Those taking clomiphene citrate should be warned that these symptoms might make activities like driving a car or operating heavy machinery more hazardous than usual. While the exact cause of these visual symptoms is not yet understood, it is advisable to discontinue treatment and have a thorough medical/opthalmological examination should they occur.
Clomiphene Citrate Side Effects
Clomiphene citrate appears to be well tolerated, with a low incidence of significant side effects. Common adverse reactions during clinical trails included ovarian enlargement (13.6%), vasomotor flushes (10.4%), abdominal discomfort (5.5%), nausea/vomiting (2.2%), breast discomfort (2.1%), visual symptoms (1.5%), headache (1.3%), and abnormal uterine bleeding (1.3%). Data also suggests that the prolonged use of clomiphene citrate may increase the chance of ovarian tumor. Clomiphene citrate is occasionally associated with a serious and potentially life threatening side effect called ovarian hyperstimulation syndrome (OHSS). Early warning signs of OHSS include abdominal pain and distention, nausea, diarrhea, and weight gain.
Clomiphene Citrate Administration
Clomiphene citrate is FDA approved for the treatment of women with ovulatory dysfunction preventing pregnancy. The recommended dosage is 50 mg daily for 5 days, which is initiated approximately 5 days into the menstrual cycle. If ovulation does not occur, follow up cycles may use a dosage of 100 mg per day for 5 days. Many clinicians recommend a limit of 6 courses of therapy.
When used by men (off-label) to mitigate the estrogenic side effects of anabolic/androgenic steroid use, a daily dosage of 50-100 mg (1-2 tablets) is usually anabolic/androgenic steroid use, a daily dosage of 50-100 mg (1-2 tablets) is usually administered while any offending steroids are taken. Note, however, that tamoxifen production back to normal levels. Here, it is usually deemed most appropriate to use as part of a multi-component post-cycle recovery program (see Post-Cycle Therapy).
Female athletes occasionally use clomiphene citrate for the reduction of estrogenicity near the time of a bodybuilding contest. In some instances this may aid in increasing fat loss and muscularity, particularly in female trouble areas such as the hips and thighs. The drug, however, often produces very troubling side effects in pre-menopausal women, and is likewise not in very high demand among this group.
Clomiphene Citrate Availability
Clomiphene citrate is widely available on the international market in a variety of brand names. It generally sells for a reasonable price, and is of low interest to counterfeiters.
Magnus Pharmaceuticals makes the product Clomid primarily for the EU and UK markets. Due to fake products appearing on the market, Magnus offers an online checker that lets steroid users verify their product originality.
Clomiphene is a synthetic estrogen clinically administered to help women ovulate. Bodybuilders, (male) following AAS cycles, seeking to jump start natural testosterone production (or those that were simply seeking a natural testosterone spike) have used this drug with great success. Clomiphene increases activity in the hypothalamus-pituitary-gonadol axis by stimulating the release of more gondotropin from the pituitary gland. Therefore, a higher/faster level of LH (luteinizing hormone) and FSH (follicle stimulating hormone) results. This creates a signal to the leydig cells in the testes which in turn produce more testosterone and sperm. Normally with Clomiphene this took 5-15 days. Most started with 50-mg twice daily for about 5 days, then reduced intake to 50 mg once a day for 5-10 more days. Due to Clomiphene providing a fast response time, I felt it was often beneficial to use a dosage of 100 mg total daily for 5 days, mid-cycle during longer AAS protocols. This drug was seldom utilized for longer than 15 days continuously simply due to it being unnecessary. The goal was to normalize testosterone production post AAS cycle as quickly as possible so as to minimize post-cycle strength and mass loss. Not create dependency.
HCG was combined with Clomiphene (Clomid) sometimes, or Clomiphene was used after HCG administration. This is because Clomiphene acts by affecting the hypothalamus and pituitary (hypophysis) and regenerating the whole regulating system, while HCG only "imitates" LH, thus stimulating the leydig cells in the testes to produce natural testosterone. (*Also see HCG)
*Some may wonder about Clomiphene being a synthetic estrogen. Yes, it is, but it works as an anti-estrogen. This is due to the fact that Clomiphene has a very low estrogenic effect. This means stronger and more active estrogen, such as those formed during the aromatization of many androgenic steroids, are blocked out of the receptor-site and less estrogenic activity results; less gyno, less water retention. Clomiphene was by no means as effective as Novladex or Proviron for estrogen suppression, but post-cycle it helped greatly.
Anabolic Steroid Guide reference
Clomid is not an anabolic/androgenic steroid. Since it is a synthetic estrogen it belongs, however, to the group of sex hormones. In school medicine Clomid is normally used to trigger ovulation. Clomid also has a strong influence on the hypothalamohypophysial testicular axis. It stimulates the hypophysis to release more gonadotropin so that a faster and higher release of FSH (follicle stimulating hormone) and LH (luteinizing hormone) occurs. This results in an elevated endogenous (body's own) testosterone level. Clomid is especially effective when the body's own testosterone production, due to the intake of anabolic/androgenic steroids, is suppressed. In most cases Clomid can normalize the testosterone level and the spermatogenesis (sperm development) within 10- 14 days. For this reason Clomid is primarily taken after steroids are discontinued. At this time it is extremely important to bring the testosterone production to a normal level as quickly as possible so that the loss of strength and muscle mass is minimized. Even better results can be achieved if Clomid is combined with HCG or when Clomid is used after the intake of HCG.
Paradoxically, although Clomid is a synthetic estrogen it also works as an antiestrogen. The reason is that Clomid has only a very low estrogenic effect and thus the stronger estrogens which, for example, form during the aromatization of steroids, are blocked at the receptors. These would include those that develop during the aromatizing of steroids. This does not prevent the steroids from aromatizing but the increased estrogen is mostly deactivated since it cannot attach to the receptors. The increased water retention and the possible signs of feminization can thus be reduced or even completely avoided. Since the antiestrogenic effect of Clomid is lower than those found in Proviron, Nolvadex, and Teslac it is mainly taken as a testosterone stimulant. Clomid is a medication that promotes the production of the body's own stimulating hormone, gonadotropin, which in turn increases the testosterone level. It is, for example, administered to women as a so-called antiestrogen to trigger ovulation ("ovulation stimulator").
Side effects of Clomid are very rare if reasonable dosages are taken. Possible side effects are climacteric hot flashes and occasional visual disturbances which can manifest themselves in blurred vision, giving flickering or flashing. Should visual disturbances occur, the manufacturer recommends discontinuing Clomid treatment. Inadequate liver functions cannot be excluded; however, they are very unlikely. In women enlargement of the ovaries and abdominal pain can occur since Clomid stimulates the ovaries. When taking Clomid multiple pregnancies are possible as well. As for the dosage, 50-100 mg/day (1 -2 tablets) seems to be sufficient. The tablets are usually taken with fluids after meals. If several tablets are taken it is recommended that they be administered in equal doses distributed through-out the day. The duration of intake has been rummored to not be taken for longer thatn 10-14 days. This is incorrect. Clinical studies with male patients have shown clomid to be used for up to a year or longer. Most athletes begin with 100 mg/day, taking one 50 mg tablet every morning and evening after meals. After the fifth day the dosage is often reduced to only one 50 mg tablet per day It is normally not necessary to take the compound for more than ten days in order to increase the endogenous testosterone production. Clomid is relatively expensive. A package with 10 tablets costs approx. $35 - 45 on the black market.
Newbies Research Guide
Estrogen receptor antagonists, more simply referred to as anti-estrogens (though this term is often loosely applied to all estrogen maintenance drugs), are drugs that block estrogens from exerting activity in the body. This is actualized by the ability of a particular substance to bind to a segment of the estrogen receptor, yet not activate it. This in turn prevents other estrogens from binding and activating the same receptor site. In a clinical setting an estrogen antagonist, most prominently the drug tamoxifen citrate (sold under the brand name Nolvadex) is typically used as the first line of defense during advanced breast cancer thera- py. Its use can efficiently deprive estrogen responsive cancer cells of necessary hormone, allowing a high rate of response in patients with such forms of cancer. Stronger agents such as aromatase inhibitors (discussed below) are usually a second choice, substituted when conventional antiestrogen therapy fails to elicit the desired response.
A drug like tamoxifen is preferred over other agents as the first course of breast cancer treatment for a number of reasons, most due to the fact that that it is both extremely effective yet does not inhibit the actual formation of estrogen in the body. Among other things, this may allow Nolvadex therapy to be somewhat more comfortable for the patient. Although many women (particularly pre-menopausal) seem to suffer menopausal-like side effects with virtually all estrogen maintenance drugs, estrogen antagonists are often somewhat more tolerable than agents that block the synthesis of estrogen. In fact the activity of tamoxifen is itself variable, such that in certain target tissues it may actually act as an agonist (activator) of the estrogen receptor. It therefore does not completely diminish the biological activity of estrogens, though it does considerably reduce it nonetheless.
It is also well understood in medicine today that estrogens play a supportive role in the cardiovascular system. For example, studies show that a rise in the estrogen level (as in post-menopausal estrogen replacement therapy) is typically linked with a reduction in LDL (bad) cholesterol, and a rise in HDL (good) cho- lesterol. The ability of tamoxifen to act as an estrogen agonist in the liver likewise gives it what may be its most welcome property, namely that it exhibits an estrogenic, rather than antiestrogenic, effect on blood lipid (cholesterol) values. As a 1998 study by the Department of Clinical Oncology in the Netherlands Cancer Institute shows, during long-term treatment with tamoxifen (6 months) a lowered LDL cholesterol level, and significantly elevated HDL cholesterol level and HDL-C/total-cholesterol ratio may result. This trend should reduce an important risk factor for heart disease, obviously a welcome effect during treatment. For the steroid-using athlete already faced with negative alterations in lipid profiles, such an effect could obviously an important consideration.
Clomid (clomiphene citrate) is very similar in structure to Nolvadex, both drugs being classified as triphenylethylene compounds and used clinically for similar purposes (breast cancer as well as female infertility treatment). As well as we see with Nolvadex, Clomid is a partial agonist/antagonist of the estrogen recep- tor depending on the target tissue in question. Although athletes most commonly think of Clomid as a testosterone-stimulating drug only (another effect of antie- strogenic compounds), to be used at the conclusion of steroid treatment, its activity in the human body is not at all dissimilar to Nolvadex. It should likewise be thought of not as a drug with its own niche of use, but instead as another efficient remedy for gynecomastia similar to Nolvadex (with the related ability to sup- port the release of testosterone). It could clearly replace Nolvadex as a preventative measure against gynecomastia during cycles with aromatizable steroids without noticeably altering the level of effect received, just as Nolvadex can be used effectively to increase the synthesis of testosterone in the body at the con- clusion of steroid use (though admittedly Nolvadex may be slightly more potent in both regards)
Wlliam Llewellyn (2011) - Anabolics
L. Rea (2002) - Chemical Muscle Enhancement Bodybuilders Desk Reference
Anabolic Steroid Guide
Newbies Research Guide