Clomiphene citrate is an anti-estrogenic drug that isprescribed to women to treat anovulatory infertility (inabilityto ovulate). In clinical medicine it is specifically referred toas a nonsteroidal ovulatory stimulant. The drug works byinteracting with estrogen receptors, often in an antagonisticmanner, in various tissues of the body including thehypothalamus, pituitary, ovary, endometrium, vagina, andcervix. One main focus is that the drug will oppose thenegative feedback of estrogens on the hypothalamic-pituitaryovarianaxis, enhancing the release of gonadotropins (LH andFSH). This surge in gonadotropins may cause egg release(follicular rupture), ideally leading to conception.Clomiphene citrate is chemically a synthetic estrogen withboth agonist/antagonist properties, and in this regard is verysimilar in structure and action to Nolvadex®. It is believedthat both the estrogenic and anti-estrogenic properties ofclomiphene citrate play a role in its ability to support femalefertility.

In men, clomiphene citrate also acts as a partial antiestrogen,and may be used to counter some of the side effectsof aromatizable steroid use including gynecomastia andincreased water retention. As an anti-estrogenic drug,clomiphene citrate may also produce an elevation of folliclestimulating hormone, and luteinizing hormone levels, whichcan elevate testosterone production. This effect is especiallybeneficial at the conclusion of a steroid cycle, whenendogenous testosterone levels are depressed. Here,clomiphene citrate is most often applied in combination withhCG and tamoxifen, in an effort to restore endogenoustestosterone production more quickly (see PCT: Post-CycleTherapy). If testosterone levels are not brought back tonormal in a short period of time, a significant loss in size andstrength may occur. This is due to the fact that withouttestosterone (or other anabolic/androgenic steroids) toimpart an ongoing anabolic message, the catabolic hormonecortisol becomes the dominant force affecting muscle proteinsynthesis. Often referred to as the post-steroid crash, whennot corrected this state of imbalance in the endocrine systemcan quickly reduce muscle mass levels, diminishing the longtermreturn on anabolic/androgenic steroid therapy.

Note that the triphenylethylene compounds (toremifenecitrate, tamoxifen citrate, clomiphene citrate) tend to besomewhat intrinsically estrogenic in the liver. This meansthat while they can block estrogenic activity in some areas ofthe body, they can actually act as estrogens in this other keyarea. Estrogenic action in the liver is important in theregulation of serum cholesterol (it tends to support HDLsynthesis and LDL reductions). Since steroid-usingbodybuilders are already dealing with the negativecardiovascular effects of these drugs, compounding the issuewith aromatase inhibitors (which will lower total serumestrogen levels) may not always be the best option. Using adrug that blocks gynecomastia, for example, while at thesame time supporting improved cholesterol values, might bemuch more ideal.

History:

Clomiphene citrate is a fertility drug with a substantialhistory of use in the United States. It first gained widespreadacceptance during the early 1970s, and has been a drugcommon to the fertility practice ever since. The drug is nowconsidered a standard medication for certain forms offertility therapy, and has been adopted as such far outsideU.S. border. Clomiphene citrate is presently available inmost nations worldwide. The two most popular brand namesone is likely to encounter are Clomid and Serofene, althoughthe drug can be found under numerous other trade names aswell including (but not limited to) Sepafar, Omifin,Pergotime, Gonaphene, Duinum, Clostil, Ova-Mit, andClostibegyt. Clomiphene citrate is generally a veryinexpensive medication compared to stronger anti-estrogenssuch as the newer selective third-generation aromataseinhibitors. It, likewise, remains a very popular agent of useamong bodybuilders and athletes.

How Supplied:

Clomiphene citrate is most commonly supplied in tablets of50 mg.

Structural Characteristics:

Clomiphene citrate is classified as a selective estrogenreceptor modulator, with both agonist and antagonistproperties. It has the chemical designation 2-[4-(2-chloro1,2-diphenylvinyl) phenoxy] triethylamine dihydrogencitrate.

Warnings (Visual Symptoms):

Some patients using clomiphene citrate notice blurring orother visual disturbances such as spots or flashes. Thesesymptoms occur more frequently at higher doses or longerdurations of therapy, and often disappear within a few daysor weeks of use. Prolonged visual disturbances have beenreported after the discontinuation of clomiphene citratetherapy, however, and in some cases may be irreversible.Those taking clomiphene citrate should be warned that thesesymptoms might make activities like driving a car oroperating heavy machinery more hazardous than usual. Whilethe exact cause of these visual symptoms is not yetunderstood, it is advisable to discontinue treatment and havea thorough medical/opthalmological examination should theyoccur.

Side Effects:

Clomiphene citrate appears to be well tolerated, with a lowincidence of significant side effects. Common adversereactions 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 abnormaluterine bleeding (1.3%). Data also suggests that theprolonged use of clomiphene citrate may increase the chanceof ovarian tumor. Clomiphene citrate is occasionallyassociated with a serious and potentially life threatening sideeffect called ovarian hyperstimulation syndrome (OHSS).Early warning signs of OHSS include abdominal pain anddistention, nausea, diarrhea, and weight gain.

Administration:

Clomiphene citrate is FDA approved for the treatment ofwomen with ovulatory dysfunction preventing pregnancy.The recommended dosage is 50 mg daily for 5 days, which isinitiated approximately 5 days into the menstrual cycle. Ifovulation does not occur, follow up cycles may use a dosageof 100 mg per day for 5 days. Many clinicians recommend alimit of 6 courses of therapy. When used by men (off-label)to mitigate the estrogenic side effects of anabolic/androgenicsteroid use, a daily dosage of 50-100 mg (1-2 tablets) isusually administered while any offending steroids are taken.Note, however, that tamoxifen is usually given preferenceover clomiphene citrate for this purpose. More commonly,clomiphene citrate is used by men at a dosage of 50-100 mgper day for 30 days at the conclusion of a steroid cycle, in aneffort to bring natural testosterone production back to normallevels. Here, it is usually deemed most appropriate to use aspart of a multi-component post-cycle recovery program (seePCT: Post-Cycle Therapy). Female athletes occasionally useclomiphene citrate for the reduction of estrogenicity near thetime of a bodybuilding contest. In some instances this mayaid in increasing fat loss and muscularity, particularly infemale trouble areas such as the hips and thighs. The drug,however, often produces very troubling side effects in premenopausalwomen, and is likewise not in very high demandamong this group.