FDA Advisory Panel Urges Restrictions on Testosterone Use.  By Miriam E. Tucker. medscape.com. September 18, 2014. A combined US Food and Drug Administration (FDA) advisory panel has voted nearly unanimously to change the labeling for testosterone-replacement products, with the aim of tamping down on their current widespread use for "age-related" hypogonadism. The panel also indicated that large studies are needed to demonstrate both clinical benefit and safety of the products. The votes of the joint Bone, Reproductive, and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee were 20 to 1 in favor of label changes, and the panel voted as follows for these respective outcomes:

• Not requiring a safety study (1 vote).• Requiring a safety study only for certain indications (16 votes).• Requiring a safety study regardless of indication (4 votes).Testosterone products have 2 current indications. The first — for replacement of testosterone in men with congenital or acquired primary hypogonadism, including conditions such as cryptorchidism, Klinefelter’s syndrome, or testicular damage from chemotherapy or heavy metals — was not in dispute.The panel primarily addressed the second indication, currently worded as "Hypogonadotropic hypogonadism (congenital or acquired): Idiopathic gonadotropin or luteinizing-hormone–releasing (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation."The "idiopathic" wording has led to the widespread use of testosterone products for men with relatively low testosterone levels related to aging as well as for men with signs and symptoms of "low T" but who in reality have either normal testosterone levels or, in many cases, do not even have testosterone levels tested."Benefit is unclear in men diagnosed with hypogonadism due to no apparent cause other than older age. Yet testosterone is being predominantly prescribed to men 40 to 64 years of age. This has prompted the FDA to question whether labeling accurately reflects the appropriate indicated population," Hylton V. Joffe, MD, director of the Division of Bone, Reproductive, and Urologic Products at the FDA, told the panel in his introductory remarks.Call for Much Tighter Wording of Second IndicationThe 2010 publication of a study showing a signal of cardiovascular risk among 209 men aged 65 and older taking testosterone-replacement therapy prompted the FDA’s initial investigation into this area, and more recently published studies suggesting both cardiovascular risk and possible protection prompted further inspection, Dr. Joffe said.An FDA analysis of national sales data found that use of testosterone therapy rose 65% from 2009 to 2013 in the United States, and the number of prescriptions rose from 1.3 million in 2010 to 2.3 million by 2013. Men aged 40 to 64 accounted for 70% of those prescribed testosterone products and were the group in whom usage rose the most during the 5-year period, FDA epidemiologist Mohamed A. Mohamoud, PharmD, told the panel.Data also show that only about half of men taking testosterone therapy had been diagnosed with hypogonadism. Furthermore, there was no evidence in 25% of users to show they had had their testosterone concentrations tested prior to initiating therapy, and 21% of those prescribed testosterone replacement had not had their levels tested at any time while they were on the therapy, Dr. Mohamoud said.