Successful Pregnancies after Spermatogenesis Induction with Letrozole in Men with Obesity-Related Hypogonadotropic Hypogonadism

Presentation Number: THR-132
Date of Presentation: March 5th, 2015

Lena Salgado*, Helene B Lavoie and Ariane Godbout
Centre de recherche du Centre hospitalier de l’Université de Montréal (CR-CHUM), Montreal, QC, Canada


Background: Obesity is increasingly recognized as a cause of infertility in men. One of the underlying mechanisms is the inhibition of gonadotropin production by estrogens aromatised from androgens in adipose tissue. Testosterone levels and sperm quality can be restored with the use of aromatase inhibitors, the most potent being Letrozole. Some series suggest that a low dose (one tablet of 2.5 mg weekly) is sufficient to normalize testosterone levels(1,2). However, data on spermatogenesis and fertility are lacking.

Objective: To review the efficacy of low-dose letrozole to normalize testosterone, sperm count, and fertility in men with obesity-related hypogonadotropic hypogonadism (OrHH).

Method: Retrospective observational study of 12 men consulting for infertility, and diagnosed with OrHH. Obesity was defined as a body mass index (BMI) greater than 30 kg/m2. All patients had a total testosterone below the lower limit of normal with normal to low FSH and LH, and/or decreased sperm count as defined by the World Health Organisation. After excluding other causes of hypogonadism, patients were given low-dose letrozole.

Results: At baseline, mean age was 35.3 ± 5.9 years and mean BMI was 43.0 ± 7.0 kg/m2. Three subjects were diabetic and two were treated for sleep apnea. Mean duration of infertility was 2.9 ± 2.0 years. Eight had primary infertility and four, secondary infertility. Partners’ mean age was 31.1 ± 5.1 years and five were treated for polycystic ovary syndrome. After starting low-dose letrozole, estradiol decreased from 119.5 ± 57.2 to 72.2 ± 35.1 nmol/L. Mean FSH increased from 4.4 ± 2.0 to 8.0 ± 2.5 IU/L, mean LH increased from 4.4 ± 1.8 to 6.6 ± 1.1 IU/L, and mean total testosterone increased from 7.4 ± 1.7 to 21.1 ± 6.9 nmol/L. Mean sperm count rose from 14.8 ± 16.2 to 64.5 ± 67.2 x 109/L.

Discussion: Three response patterns were identified: full responders (increase in testosterone and sperm count; three patients), mixed responders (increase in testosterone but not in sperm count; two patients), and non-responders (one patient). Six patients’ sperm counts are pending, but testosterone levels normalized in eleven patients (92%). Three couples conceived: two spontaneously and one with in vitro fertilization. Four pregnancies ensued:  two reached term, successfully; the other two were a spontaneous abortion and an ectopic pregnancy.

Conclusion: Letrozole seems to be an effective treatment to help restore fertility in obese infertile men, with an interesting safety profile and some great advantages in term of route of administration and cost when compared to the use of gonadotropins injections for spermatogenesis induction. More studies are needed to determine which patients might benefit most from this treatment, as well as to compare it with other treatments such as gonadotropins and clomiphene citrate.


Nothing to Disclose: LS, HBL, AG