It's Time To Cross The T's...

(RTTNews) - Testosterone, often considered as the "fountain of youth", is the major sex hormone in men, and as they age the level of this hormone also naturally declines. The condition in which the body doesn't produce enough testosterone, also known as hypogonadism or simply, Low T, is associated with specific signs and symptoms, including diminished sex drive and sense of vitality, erectile dysfunction, mood disturbances, fatigue and osteoporosis.

Although Low T is especially common in older males, it can also occur at any age, and that can be due to inherited conditions, disease, injury, drugs, and certain types of cancer.

Testosterone replacement therapy (TRT) is often recommended to provide and maintain a normal level of testosterone. TRT is available in several forms like skin patch, gels, mouth patch, injections and subcutaneous implants.

Although testosterone products are FDA-approved only for use in men who lack or have low testosterone levels in conjunction with an associated medical condition, they are also being widely used without a diagnosis of low testosterone by young men seeking to improve strength, athletic performance and physical appearance, and older men who want to ward off signs of aging.

Such has been the aggressiveness of marketing campaigns that testosterone replacement therapy in the elderly has increased more than 300% in 15 years, according to a study by Institute for Clinical Evaluative Sciences and St. Michael's Hospital.

Sales of testosterone products, which were a mere $324 million in 2002, have now grown to nearly $2 billion, and is expected to touch $5 billion by 2018, according to IMS Health.

AbbVie's AndroGel; Eli Lilly's Axiron; Pfizer's Depo-Testosterone; Actavis' Androderm; Valeant Pharmaceuticals' Android; Auxilium Pharmaceuticals' Strian and Endo Pharmaceuticals' Fortesta are some of the leading prescription testosterone drugs.

While proponents say that testosterone replacement therapy can help elderly men improve their quality of life, opponents have been raising concerns about the harmful effects that testosterone drugs might have on the aging body.

An observational study of older men in the U.S. Veteran Affairs health system, published in the Journal of the American Medical Association (JAMA) in November 2013, suggested that there was a 30 percent increased risk of stroke, heart attack, and death in the group that was prescribed testosterone therapy.

A second observational study reported an increased risk of heart attack in older men, as well as in younger men with pre-existing heart disease, who took testosterone therapy.

The studies linking testosterone replacement therapy to heart complications in men prompted the FDA to re-consider the risks and benefits of TRT.

Accordingly, a joint Advisory Committee meeting was held on September 17, 2014 to re-assess the cardiovascular safety of testosterone therapy as well as to identify the appropriate patient population for whom TRT should be indicated.

The FDA panel voted 20-1 recommending label changes to all testosterone drugs to limit the intended uses of the drugs, particularly in relation to age-related low testosterone. This could mean a restriction in the off-label use of TRT by men who do not meet the FDA-specified criteria of both low testosterone levels and an associated medical condition.

While the panel concluded that there is insufficient evidence that testosterone use leads to an increased risk of cardiovascular events, it has recommended that companies be required to conduct additional studies to assess the cardiovascular risk of their products for patients with age-related low testosterone.

The FDA panel's recommendations have spooked the shares of pharmaceutical companies developing testosterone drugs.

As of this writing,

-- Lipocine Inc. (LPCN), whose oral testosterone therapy product, LPCN 1111, is in phase II testing have plunged over 32% to $5.09.

-- Repros Therapeutics Inc. (RPRX), whose lead product candidate Androxal is under phase III studies for men of reproductive age with low testosterone, has dropped more than 21% to $10.09.

-- Testosterone therapy manufacturer Acrux Limited, which is traded on the ASX, has fallen 26% to A$1.25. Acrux developed Axiron, the first testosterone topical solution, and licensed the worldwide rights for the product to Eli Lilly in 2010.

In related news, the FDA Advisory Committee which reviewed privately-held Clarus Therapeutics Inc.'s New Drug Application for REXTORO for low testerone in men on Thursday has given thumbs down to the product.

The panel members voted 18-3 that the overall benefit/risk profile of REXTORO was not acceptable to support approval for testosterone replacement therapy. The panel also voted 12-8 with one abstention that there was not sufficient evidence that REXTORO is effective.

In July of this year, based on the available evidence, the Health Canada concluded that there is a possibility that cardiovascular problems may occur with the use of testosterone replacement products. The Canadian drug regulator also required testosterone therapy manufacturers to update the Canadian product label regarding possible cardiovascular risks including heart attack, stroke, blood clots in the lungs or legs, and irregular heart rate.