Trade name: Clomid
Clomiphene is a selective estrogen receptor modulation (SERM) that competitively binds to estrogen receptors in the hypothalamus and in the pituitary gland, among other places in the body. Estrogen normally has a negative feedback action on the hypothalamus and pituitary gland, so when the actions of estrogen on these structures are blocked, the result is increased secretion of LH and FSH from the pituitary gland. The extra LH secreted then stimulates the Leydig cells in the testicles to make more testosterone. If FSH levels are inappropriately low, then an increase in FSH secretion can also increase sperm production.
The ability of clomiphene to increase testosterone levels is roughly comparable to that of testosterone gels. Since clomiphene works by increasing LH production by the pituitary gland, if the LH is already elevated (indicating Leydig cell dysfunction), then clomiphene will not be as effective. In men with a baseline LH of over 20 IU/L prior to any medication, clomiphene is not likely to work very well.
Clomiphene and Estradiol Levels
Another important consideration is that clomiphene can increase levels of estradiol in some men. The enzyme aromatase converts some of a man’s testosterone to estradiol. If clomiphene is started and testosterone levels increase, then more of this T can be converted to estradiol. Therefore, estradiol levels should be monitored in men on testosterone-enhancing therapies.
How Clomiphene Is Used
Clomiphene is taken by mouth. Unlike in women, who typically need to take higher doses of clomiphene on certain days of their cycle, clomiphene in men is taken on a daily (or every other day) basis at lower doses. The typical starting dosage in men is 25 mg a day. Clomiphene comes in 50 mg tablets; some clinicians recommend taking one 50 mg tab every other day, while I typically use 25 mg daily (a pill cutter can be used to halve the 50 mg tablets).
Here is a sample range of dosages:
• 25 mg every third day
• 25 mg every other day
• 25 mg every day (typical starting dosage)
• Alternate 25 mg daily with 50 mg daily
• 50 mg daily
• Alternate 50 mg daily with 75 mg daily
• 75 mg daily (I usually do not go above this dosage, although I have seen clinicians use up to 100mg daily)
Because clomiphene is much more commonly used in women than in men, I have had pharmacists who are unfamiliar with the treatment of male infertility call the office to question the accuracy of a clomiphene prescription when they see that it is written for a man. I have therefore taken to printing “This is for a male patient” on my clomiphene prescription sheets to decrease the number of phone inquiries from pharmacists.
Cost of Clomiphene
Clomiphene may be covered by your insurance company. However, if you do not have insurance coverage for your medications, the price of clomiphene at some regional and fertility-specific pharmacies is reviewed in the "Fertility Medications Cost" section of this website.
Clomiphene has a bad reputation in terms of side effects, since it can provoke significant mood swings in the women who use it. In men, clomiphene has a good safety profile, and men also do not typically have the same negative mood-related side effects with clomiphene that women do. Most men feel no different while taking clomiphene, and some actually feel better in terms of mood, energy, and libido due to the increased testosterone levels. Adverse side effects do occur in about 5 percent of men taking clomiphene, although these are usually mild. Potential side effects include:
1) Visual disturbances. Blurred vision, spots in vision, and flashes of light are the most common side effects that I have seen in men taking clomiphene, although they only occur in a small number (less than 2 percent) of them. Generally, the visual side effects resolve within a few weeks of lowering the dosage or stopping the medication. Men with a history of central retinal vein occlusion (CRVO) should consult with their ophthalmologist before starting clomiphene.
2) Gynecomastia (male breast enlargement). This is the result of elevated estradiol levels, so this side effect should be rare if estradiol levels are followed and kept within the normal range
3) Weight gain. Typically this is minimal.
4) Hypertension. Blood pressure should be checked regularly; if it seems to be high, let your doctor know.
5) Cataracts. An easy, painless exam can check for this.
6) Acne. This is due to increased skin gland oil production; it usually subsides after a few months of treatment.
7) Dizziness or headache. More likely at higher doses.
8) Gastrointestinal symptoms. Stomach upset or nausea have been noted in a few patients.
9) Other symptoms. Additional side effects that have been seen include insomnia, hair loss, and allergic dermatitis. Aggressive behavior has been noted, though it is a very uncommon side effect.
If you experience any of these negative side effects, it is best to stop the medication and contact your doctor.
Congenital Vascular Abnormalities
There is some concern about using clomiphene in men with congenital vascular abnormalities (such as Klippel-Trenaunay syndrome) due to the potential impact on estrogen receptors within the abnormal vessels. Therefore, anastrazole or HCG may be a better choice in these patients.
Clomiphene and Osteoporosis
Since there are estrogen receptors in the bone, there are concerns that long-term use use of clomiphene may increase the risk of bone weakness (osteoporosis), however, the long-term impact of clomiphene on bone density is controversial. Some studies have shown improvements in bone density in hypogonadal men on clomiphene, while others show decreases in bone density while taking this medication. See the “Osteoporosis” section of this website for more information about osteoporosis management.