A letrozole pill once a week restored fertility in obese, infertile men and led to their partners giving birth to two full-term, healthy babies, according to a new study from Canada. The results will be presented Thursday at the Endocrine Society’s 97th annual meeting in San Diego.
“To our knowledge, this is the first report of successful pregnancies with the use of letrozole at this low dose in men,” said the study’s lead investigator, Lena Salgado, MD, an endocrinology fellow at the Centre Hospitalier de l’Université de Montréal (CHUM).
Letrozole is approved by the Food and Drug Administration for treatment of estrogen receptor positive breast cancer in postmenopausal women and is used “off-label” in infertile women to induce ovulation.
Some recently published studies have suggested that in men with obesity-related low testosterone, a low dose of letrozole can normalize testosterone levels.
Doctors think obesity can cause infertility in men because excess fat results in too much estrogen. The body’s aromatase enzyme, which is more prevalent in fat, converts androgens (male hormones, such as testosterone) into estrogen. Letrozole inhibits this action of aromatase.
Salgado’s group studied the medical records of 12 obese men who sought treatment for infertility and received a diagnosis of obesity-related hypogonadotropic hypogonadism. This form of low testosterone occurs when the pituitary gland, which signals the testicles to produce testosterone, sends signals that are too weak to stimulate the gonads. A low sperm count also can result.
It’s ironic that Letrozole, a drug meant to cure breast cancer and also used for infertility is causing genetic malformations, and even cancer in babies.
It’s a drug used to treat breast cancer world over. But in India, Letrozole is also approved and popularly used for treating infertility in young women.
Research shows that it causes genetic malformations of the bone, cardiac disease and even cancer in babies of women who consumed Letrozole.
On average, the men had been infertile for nearly three years. The men received a 2.5-milligram letrozole pill every week. Their follow-up ranged from two to 21 months.
One man did not tolerate the treatment because of headaches and switched to treatment with another aromatase inhibitor drug, anastrozole, but was included in the analysis. A different man did not respond to letrozole treatment. According to Salgado, he had other health problems, including uncontrolled diabetes, which could also affect the level of testosterone and/or quality of sperm.
In the remaining 11 patients, testosterone levels rose to normal, study data showed. The level of estradiol, a type of estrogen, decreased substantially in most men as well.
Three couples conceived (one of whom used in vitro fertilization), and four pregnancies ensued, Salgado reported. Two pregnancies were successful births. One ended because of an ectopic pregnancy (fetus growing outside the womb), and one was a miscarriage.
Letrozole treatment is less expensive and easier than the usual treatment involving hormonal injections of human chorionic gonadotropin, or hCG, Salgado stated.
Infertility experts in India though defend that this drug is very effective and has not been observed to cause a higher rate of genetic malformations in babies.
“Letrozole is effective in at least 35 per cent of infertility patients. Also uterine Tuber Closes (TB) is very common in India and Letrozole is effective in these patients,” In-Vitro Fertilization expert Dr Manika khanna said.
Drug Controller General of India has finally directed the Indian council of Medical Research (ICMR) to conduct fresh clinical trails on Letrozole.
But whether or not Letrozol gets a nod from ICMR, the fact is that this drug was being used on the general population without being tested for safety for at least five years.
“The dose of hormonal injections needed to obtain normal testosterone levels and sperm production is proportional to weight, so in obese men, the cost becomes excessive,” she said. “Letrozole is a very attractive fertility treatment for men with obesity-related hypogonadism.”
The Endocrine Society
ENDO 2015: The 97th Annual Meeting & EXPO in San Diego, CA