Anti-estrogen may benefit some men with idiopathic HH

February 1, 2006

Montreal--The anti-estrogen agent clomiphene citrate (Clomid, Milophene, Serophene) may provide an easier, less expensive treatment for infertility among some men with hypogonadotropic hypo-gonadism [HH], according to a small retrospective study. The agent may be worth trying before the more expensive and difficult-to-administer gonadotropins are employed.

Montreal-The anti-estrogen agent clomiphene citrate (Clomid, Milophene, Serophene) may provide an easier, less expensive treatment for infertility among some men with hypogonadotropic hypo-gonadism [HH], according to a small retrospective study. The agent may be worth trying before the more expensive and difficult-to-administer gonadotropins are employed.

Hypogonadotropic hypogonadism is defined as the failure of the testes to produce sperm and/or testosterone. Post-puberty, patients with the condition usually present with a loss of libido or infertility. Traditional therapies include gonadotropins and gonadotropin-releasing hormone (GnRH) pumps, said Scott J. Whitten, MD, a fellow and instructor in the department of obstetrics and gynecology, division of reproductive endocrinology and infertility, University of Alabama at Birmingham School of Medicine.

An alternative is administration of clomiphene, which has been used with varied success to treat secondary hypo-gonadism. This agent reliably increases gonadotropin and testosterone levels, but has a variable effect on spermatogenesis, said Dr. Whitten, who conducted a study of the agent with Peter Kolettis, MD, and Ajay K. Nangia, MD.

The researchers reviewed the medical records of 10 men who had been evaluated for infertility and who were subsequently diagnosed with HH. Four of these men had Kallman's syndrome, four had idiopathic HH, and two had panhypopituitarism.

All patients with Kallman's syndrome were azoospermic and had gonadotropin levels less than 1 mIU/mL at presentation. Only one of these patients had never been on hormone replacement therapy, and he had a baseline testosterone level of 22 ng/dL.

Standard gonadotropin therapy allowed patients to achieve normal testosterone levels. One patient experienced an increase in sperm concentration and achieved a pregnancy, but the spermatogenic response took nearly 2 years.

Idiopathic HH patients respond

Among patients with idiopathic HH, three were azoospermic and one was severely oligospermic. Mean testosterone was 109 ng/dL, mean follicle stimulating hormone (FSH) was 1.6 mIU/mL, and mean lu-teinizing hormone was 1.5 mIU/mL for this group. One man with idiopathic HH admitted to having used anabolic steroids for less than 1 month about 5 years prior to his presentation. Another patient was already on clomiphene at presentation, which increased gonadotropin and testosterone levels, but not his sperm count.

Those who had not yet taken clomiphene were started on a dose of 50 mg three times per week, and the patient who had not had a spermatogenic response to the drug was switched to traditional go-nadotropin therapy.

All idiopathic HH patients responded to therapy within 4 to 6 months with an increase in testosterone levels. Two patients taking clomiphene had repeat gonadotropin levels drawn that had returned to within normal range. All four patients had a spermatogenic response ranging from 10 to 163 million/mL. Three have achieved pregnancies thus far.

Additional findings

Among patients with panhypopituitarism, one was oligospermic and the other was azoospermic. Both patients discontinued the testosterone therapy they had been taking at presentation.

One started human chorionic go-nadotropin (HCG) therapy three times per week, but had to discontinue due to a secondary recurrence of cancer. The second was started on clomiphene because he had residual signs of pituitary gonadotropin secretion. After 4 months, however, testosterone levels for this second patient declined, and he was switched to HCG and FSH. He remained azoospermic.

"In summary, among patients with Kallman's syndrome who were treated with gonadotropins, two out of four patients had a testosterone response, and one out of four had a spermatogenic response. One patient did achieve pregnancy," Dr. Whitten said.

"In the idiopathic hypo-hypo group given clomiphene citrate, all three patients had a response in terms of testosterone and gonadotropin levels and spermatogenesis, and one patient who initially had a suboptimal response to clomiphene citrate and who was switched to go-nadotropins did have an increase in testosterone and spermatogenesis. Three out of four patients achieved pregnancy in this group."