Clomiphene Information Guide
What is Clomiphene?
Clomiphene is a synthetic medication which has the ability to imitate the function of hormones produced by the human body known as Selective Estrogen Receptor Modulators (SERMs). In short, Clomiphene impacts the way that the hypothalamus registers Estrogen, in order to encourage the body to produce hormones related to ovulation in women and the production of Testosterone and sperm in men. There are three forms of Clomiphene available in the pharmaceutical market: Omifin, Clomid, and Androxal. Clomiphene is also available in generic form.
In the United States, the drug is named Clomiphene, but based on international standards, it is named Clomifene. This drug is taken orally, and, dependent upon the formulation, is a light yellow or white tablet.
Clomiphene and Female Fertility
Clomiphene was first used as a fertility treatment for women. There are two forms of infertility for which Clomiphene has proven exceptionally useful—oligoovulation and anovulation.
What is Oligoovulation?
Oligoovulation refers to ovulation which occurs irregularly or infrequently during the menstrual cycle. Under normal circumstances, women ovulate about two weeks into their menstrual cycle, but certain circumstances can get this release off track. In some cases, women only ovulate around once every fifty days or more, and under other circumstances, ovulation can simply occur at the wrong time of the cycle.
As a result of this irregularity, it is difficult for women to know exactly when conception is most possible. Clomiphene can help regulate this process, making ovulation occur more regularly and predictably.
What is Anovulation?
Anovulation is a condition in which the menstrual cycle occurs, but ovulation does not happen, which prevents the possibility of conception. Clomiphene is often used to encourage ovulation to take place in a normal fashion.
Clomiphene for General Infertility
There are strong clinical results for the use of Clomiphene for these purposes, but for fertility without known causes, the body of evidence is incomplete with regard to the effectiveness of Clomiphene Fertility Treatment.
However, there is evidence that Clomiphene can boost fertility in patients with unknown causes of infertility. Clinical studies have varied with regard to Clomiphene for this purpose. Under these circumstances, Clomiphene is shown to increase fertility to around a 5.6% chance of conception per menstrual cycle, an increase in fertility of 1.4%-4.3% dependent upon the study.
Clomiphene for Multi-Modal Fertility Treatment
Clomiphene Citrate is often combined with other forms of fertility treatment in order to further increase the odds of conception.
How is Clomiphene Prescribed for Women?
Generally, for female fertility treatment, Clomiphene Therapy begins at fifty milligrams per day for five days, beginning in the third, fourth, or fifth day of the menstrual cycle. In doing so, it encourages ovulation at a normalized and stable point of the menstrual cycle. In the week prior to ovulation, which will occur between the 15th and 18th day of the cycle, the couple should copulate frequently in order to optimize the chance of fertility success.
In many cases of feminine infertility, the physician will perform tests to monitor for the surge in Luteinizing Hormone which encourages ovulation and is spurred by Clomiphene, and these tests generally take place beginning on the day that the fifth dose of Clomiphene is taken, and are administered daily until ovulation occurs, as shown by affirmative Luteinizing Hormone Testing. If ovulation does not occur by the 18th day, the fertility doctor may force ovulation through a 10,000 IU dose of Human Chorionic Gonadotropin, if there is a follicle of sufficient size for implantation.
Interestingly enough, HCG triggering is not as effective at inducing pregnancy as monitoring and waiting for the natural release of Luteinizing Hormone.
How Is Ovulation Monitored?
There are a number of ways to keep track of cycling induced by Clomiphene Citrate:
Vaginal Ultrasound – Using ultrasound, it is possible to monitor the development of Ovarian Follicles necessary for implantation and which form preceding the release of the egg. Evidence of ovulation can also be obtained via ultrasound.
Luteinizing Hormone Testing – Luteinizing Hormone Levels increase in the days preceding ovulation, or are artificially increased to induce ovulation.
Estradiol Levels – These levels are generally tested four to six days after the last Clomiphene Dose, and can also provide evidence of impending ovulation.
Progesterone Levels – Between seven and nine days past ovulation, Progesterone Levels should be a minimum of ten nanograms per milliliter for optimal chances of fertilization.
Testing for Active Sperm – Tests can be conducted in the days preceding ovulation to make sure there is sufficient active sperm present for a reasonable chance at successful conception.
By Inducing Consecutive Menstrual Cycles – By administering the Clomiphene monthly, this further encourages a healthy and normal menstrual cycle. Clomiphene treatment can be administered five of every thirty days, to produce a stable pattern. If ovulation does not occur in a cycle, the dose of Clomiphene administered is often increased by fifty milligrams per cycle over the course of six months. When used as a fertility treatment, Clomiphene is only recommended as a six month maximum course of treatment.
Side-Effects of Clomiphene for Female Fertility
Most women experience no significant side-effects resulting from Clomiphene Citrate Fertility Treatment. The most reported side-effect of Clomiphene is an enlargement of the ovaries. This occurs in less than ten percent of patients treated, and is completely reversible.
All other side effects occur in less than ten percent of patients. The most common among these side effects are:
Abnormal Bleeding from the Uterus
Temporary Changes in Vision, including Scotoma (blind spots), Photophobia (light sensitivity), Floaters, Diplopia (double vision), and Blurred Vision
A very small percentage of patients, less than one percent, experience the following symptoms:
Reversible Hair Loss (Alopecia)
Hypertriglyceridemia (elevated triglyceride levels)
Like many other forms of fertilization treatment, Clomiphene increases the likelihood of triplets and twins resulting from the release of multiple eggs (ten percent of patients that conceive using Clomiphene have twins).
Potential Long Term Risks of Clomiphene Therapy for Women
There is limited research that provides inconclusive evidence that the use of clomiphene for more than twelve months can elevate the risk of Ovarian Cancer. It may be that long term use of Clomiphene only impacts patients that don't become pregnant over the course of a year, which is why the therapy is generally only recommended for six months for women.
There have been no studies that have reproduced these risks, so there are many that believe that Ovarian Cancer risk is not affected by Clomiphene.
Clomiphene Does Not Lead to Neonatal Complications
There are no signs that suggest that Clomiphene increases the risk of Genetic Abnormalities as compared to the normal process of conception. Clomiphene also does not lead to increased risk of spontaneous abortion.
How Does Clomiphene Work?
Clomiphene works by reducing the ability of Estrogen to activate receptor-sites on the Hypothalamus. When the Hypothalamus receives stimulus from circulating Estrogen, it reduces signals from the production of Luteinizing Hormone by the Pituitary Gland. There is a similar pharmaceutical, known as Zuclomifine that acts in the same manner, but for a long a longer period of time. Although Clomiphene affects the release of steroid hormones, Clomiphene is not itself a steroid.
How Do Normal Women Reach Ovulation?
When women experience normal menstrual cycles, Progesterone and Estrogen Levels increase significantly, as released by the Corpus Luteum. This inhibits the production of Luteinizing Hormone, Follicle-Stimulating Hormone, and Gonadotropin-Releasing Hormone from the anterior pituitary and the Hypothalamus.
It is during this period where fertilization occurs, and if the body doesn't experience fertilization in the days after ovulation takes place, the Corpus Luteum breaks down because it does not receive Human Chorionic Gonadotropin signaling. HCG is released after fertilization to encourage stable Estrogen and Progesterone levels.
When used as a fertility treatment, Clomiphene is administered orally in the early stage of the menstrual cycle. During this period, levels of Follicle Stimulating Hormone increase quickly, which leads to the production of follicles in the uterus. The follicles then produce Estrogen which circulates through the blood stream. Clomiphene increases the production of Follicle Stimulating Hormone by reducing the negative feedback mechanism caused by Estrogen upon the receptors on the Hypothalamus, causing the Hypothalamus to produce quick pulses of Gonadotropin-Releasing Hormone.
As Follicle-Stimulating Hormone Levels increase, this causes the ovaries to produce more follicles, which spurs ovulation as they rupture. When using Clomiphene, ovulation generally occurs six or seven days after the last dose of Clomiphene is taken.
Clomiphene is a combination of two isomers of the same compound, Zuclomiphene and Enclomiphene. These are the active ingredients, which both have the capability of encouraging the production of Estrogen while also inhibiting the activity of negative feedback mechanisms which discourage the production of Estrogen by the female body.
In men, Clomiphene encourages the production of Testosterone by inhibiting negative feedback mechanisms, because the precursor hormones which lead to the production of Estrogen in females lead to the production of Testosterone in males.
Clomiphene Off-Label Uses
Clomiphene has proven to be highly effective for males that are experiencing Andropause, or other forms of primary hypogonadism which slow down the production of Gonadotropin-Releasing Hormone, Luteinizing Hormone, and Follicle-Stimulating Hormone.
As a result of its high effectiveness and lower incidence of side-effects, many patients and physicians prefer Clomiphene to Bio-Identical Testosterone for many patients suffering from Low-T. This is primarily because Clomiphene is cheaper than Testosterone while also being easier to administer, since it is taken orally.
Another reason why many patients prefer Clomiphene is because Clomiphene Testosterone Restoration sustains fertility during treatment while also preserving the normal form and function of the testes. With Bio-Identical Testosterone Therapy, the testes slowly lose their ability to produce sufficient levels of sperm for fertility, although this can be prevented by combining HCG Injections with Testosterone to maintain the body's production of Luteinizing Hormone, necessary for natural Testosterone and Sperm Production.
It is important to note, however, that Clomiphene has not been approved by the FDA for male use. This is not because of any inherent issue with the therapy, but because there is no profit motive for pharmaceutical companies to lobby the FDA for approval, because Clomiphene is available in generic form, and most patients use Bio-Identical Testosterone in spite of its disadvantages, as a result of a number of factors, including branding distribution. Enclomiphene, one of the two isomers that comprise Clomiphene, is in the process of clinical testing for male patients, and is also known as Androxal.fffff
Use of Clomiphene as a Performance Enhancing Drug
Clomiphene is often used by men that abuse Testosterone in order to counteract the effects of the conversion of Testosterone into Estrogen. Steroid and Testosterone Abuse is generally conducted in cycles which last months, in which the user takes breaks to help encourage normal physiological function. Clomiphene is generally used between cycles in order to prevent gynecomastia and other side-effects of Steroid Abuse. This also simultaneously encourages the male body to produce its own Testosterone more quickly after a cycle.
Because of these uses, Clomiphene is included among Testosterone, Human Growth Hormone, and many other drugs on the list of banned PEDs in various international athletic leagues and competitions.
The History of Clomiphene
Clomiphene was first used in the 1960s as a medical treatment. At first it was used for women suffering from abnormal ovulation, and was later approved for use for women that had trouble ovulating at all.
In 1989, Clomiphene was also approved as a method to ascertain fertility in female patients. It was discovered that women that were capable of pregnancy would gain Bone Mineral Density via their use of the drug, while women that were unable to conceive and bear children would not experience this change in bone mass.
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