Clomiphene citrate may help men with acromegaly

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Men with acromegaly that isn't controlled by surgery and somatostatin receptor ligands (SRLs) may do better with clomiphene citrate (CC) added to their current treatment, a new study from Brazil suggests.

Clomiphene citrate is cost effective and may improve testosterone levels in patients with concurrent central hypogonadism, the authors reported online March 4 in the Journal of Clinical Endocrinology & Metabolism.

"The study shows a new option, using an old and relatively inexpensive drug for the treatment of acromegaly. With a relatively affordable drug, an important reduction on IGF-1 (insulin-like growth factor-1) levels was obtained in patients whose disease was still active and who were on other treatments when clomiphene citrate was added," Dr. Felipe Henning Gaia Duarte, of the University of Sao Paulo, told Reuters Health by email.

In Brazil, 50 mg of clomiphene citrate costs about $40 U.S. per month, compared with an estimated $6,000 U.S. per month for pegvisomant, the next treatment choice.

Asked how often acromegaly is not controlled by conventional therapies, Dr. Andrea Giustina, of the University of Brescia, Italy, told Reuters Health by email, "Applying the stringent consensus criteria for biochemical control of acromegaly, the disease is cured by surgery (by the most experienced hands) in about 50% of patients."

"According to studies, patients with residual disease are controlled by treatment with conventional medical therapy (long-acting somatostatin analogs such as octreotide LAR and lanreotide autogel) in a percentage ranging from 20% to 50%," added Dr. Giustina, who was not involved in the study.

Dr. Duarte and colleagues enrolled 16 men, ages 36 to 79, with IGF-1 above the upper limit of normal for at least one year despite medical therapies, and low testosterone levels.

The researchers measured hormone levels before and during the study. For three months, they added 50 mg/day of the selective estrogen receptor modulator (SERM) clomiphene citrate to the men's previous treatment.

Serum IGF-1 levels decreased by 41% (424 ng/mL to 250; p<0.0004) and seven patients (44%) achieved normal IGF-1 levels. Total serum testosterone levels increased by 209% (from 282 ng/dL to 497 ng/dL) and reached normal levels in four (67%) of the patients considered hypogonadal.

Dr. Guistina wrote, "The originality of this study is that, while estrogens and other SERMS are only indicated for use in females, clomiphene citrate has been studied and used in males for treating mainly infertility and hypogonadism, although off-label. Therefore, this drug may potentially be used for enhancing control of IGF-I levels in some male patients with disease only partially controlled by somatostatin analogs (not of growth hormone, since the effect is peripheral)."

Dr. Philippe Chanson of the University Paris-Sud in France, who was not involved in the study, wrote in an email, "These results do not surprise me with regard to the known effect of estrogens and SERM on growth hormone sensitivity and previous publications in that field. On the other hand, I am surprised by the importance of the effects and the fact that such a high proportion of patients achieve normalization of IGF-1."

He added, "I have concerns about side effects, which were not ascertained as in a drug trial. With regard to thrombosis risk, I would have been more comfortable with prospective data on side effects."

Dr. Duarte added in an email that he and his colleagues are continuing their research to explore clomiphene citrate's safety, efficacy, and cost-effectiveness.

The authors report no external funding.

SOURCE: http://bit.ly/1KSofdw

J Clin Endocrinol Metab 2015.

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