how it works

Clomiphene works in the opposite way to the female hormone oestrogen. The drug thus behaves like an “anti-oestrogen” and convinces the body the oestrogen level is low. In response, the body produces all the necessary hormones needed for the follicle growth. It stimulates the brain to release follicle stimulating hormone (FSH) and luteinizing hormone (LH), the hormones that are essential for ovulation.

Clomiphene actually stimulates ovulation indirectly. It works at the level of the hypothalamus and thereby ensures an increased release of gonadotrophin releasing hormone (GnRH). At the same time, the pituitary gland becomes more sensitive to GnRH, resulting in an increased production of FSH and LH increasing the chances of ovulation.

The anti-oestrogen properties of clomiphene can also have an influence upon other organs. Some women notice that their cervical mucus doesn’t become thin and elastic, as it normally would around the time of ovulation. The womb lining (endometrium) may also not be sufficiently prepared to receive an embryo. In order to monitor this, the thickness of the endometrium is also monitored at every check-up.

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how it is used

Clomiphene is taken orally in tablet form over a five-day period, generally starting on day 3-7 of your cycle (day 1 is the first day of complete menstrual bleeding). You can, in some cases, monitor its effect yourself by keeping a record of your basal body temperature. However, your doctor will decide on the best strategy for monitoring taking into account the reasons why you have been prescribed clomiphene and the aim of treatment.

Doctors mostly prefer patients to visit them in their practice. The first clomiphene is often very carefully monitored until ovulation has occurred. If the correct dosage for you is identified, then check-ups in the following cycles can be more relaxed. However, because multiple follicles can develop in reaction to clomiphene, ultrasound of the ovaries is often carried out in order to follow the development of the follicles.

If clomiphene is only being used for ovulation induction, then couples are advised to have intercourse every second day for a week, starting a few days after the last day therapy is taken.

There is no perfect formula for predicting the correct daily dose for each woman. Treatment normally begins with a 50 milligram tablet once a day for five days. There is a connection between body weight and dosage. If the first course does not cause ovulation, the daily dose is raised by one tablet for the second course. The dosages are increased by 50 milligrams until 150 milligrams (3 tablets) is reached. It is rare to achieve success at 200 milligram or 250 milligram and so these dosages are not used. If ovulation has not occurred at 150 milligrams, the clomiphene course is viewed as having failed and other treatments used.

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possible side effects

In principle, every drug can cause side effects, of varying degrees of severity. However, not everyone will experience side effects with a particular drug.

Because clomiphene works as an anti-oestrogen, there may be side effects that are caused by a relative insufficiency of the female hormone (a situation that in some respect can be compared to menopause).

• Approximately 10% of patients report experiencing hot flushes.
• Over 5% of patients report a swollen abdomen, a puffy feeling, pain and sensitivity.
• Approximately 2% of patients report feeling discomfort in their breasts, nausea and vomiting.
• Less than 2% of patients report symptoms relating to eyesight, headaches or hear loss.
• 5% of patients develop cysts.
• Clomiphene causes tough cervical mucus, because the body thinks that the oestrogen level is low, which can hinder the success of fertilisation.
• An increased (but controllable) chance of multiple pregnancy.

The use of clomiphene has also been associated with an increased risk of ovarian cancer - although such a link has never been proved. It is known that women without children, who have always had problems with their cycle and who have used clomiphene have a slightly higher chance of ovarian cancer than other women. However, this could also be caused by the underlying disorder in the ovaries rather than drug therapy. A relationship between infertility and ovarian cancer was apparent before the introduction of these drugs. Nevertheless, it is still always a good idea to avoid using this unnecessarily for too long.

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results

Clomiphene is used in a number of different treatments. As such, the chance of success depends on the reasons for its use. In terms of ovulation induction: “With well-selected patients, 80% can expect to ovulate while 40% can expect to become pregnant”, according to Speroff, et al, authors of the textbook Clinical Gynecologic Endocrinology and Infertility. Approximately 75% of pregnancies occur within the first three treatment cycles. The percentage of pregnancies per ovulation cycle lies around 15%. Almost 5% of the pregnancies are multiple  (nearly all twins).

Couples must not be discouraged if the use of clomiphene does not result in pregnancy. This is the mildest of a diverse range of fertility treatments. If the treatment does not result in a successful pregnancy, doctors may combine clomiphene with other drug therapies, or opt for another approach.

The diagram below represents the cumulative or running percentage of successful pregnancies for women who do not regularly ovulate and have used multiple courses of clomiphene citrate.

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