Finasteride and Fertility: Case Report and Review of the Literature

December 2012 | Volume 11 | Issue 12 | Case Reports | 1511 | Copyright © December 2012


Giuseppe Ricci MD, Monica Martinelli BS, Stefania Luppi PhD, Leila Lo Bello MD, Michela De Santis MD,Kristina Skerk MD, and Gabriella Zito MD

gastroesophageal re!ux disease and sporadically with 2 mg of bromazepam for mild generalized anxiety disorder. He had used minoxidil topical solution for hair loss for approximately 4 years, until 1999. He then continued with 1 mg of oral finasteride daily for an additional 10 years, which he had discontinued 3 months before our evaluation.
The patient had no history of sexual dysfunction, and physical examination was unremarkable. The first semen analysis showed severe oligospermia: volume 4.2 mL; sperm count 3.5 x 106/mL, and 30% progressive motility. Color Doppler ultrasound showed no varicocele and revealed only a mild decrease in left testicular volume. Serum hormonal levels were: follicle-stimulating hormone 6.6 mIU/mL, luteinizing hormone 4.2 mIU/mL, estradiol 16 pg/mL, prolactin 8 ng/ mL, testosterone 6 ng/mL, free testosterone 15.5 pg/mL, and dehydroepiandrosterone sulfate 133 ng/mL. The patient was advised not to resume finasteride therapy.
A second semen analysis was performed 1 month later, and an increase in sperm concentration was found: volume 4.2 mL, sperm count 12 x 106/mL, and 29% progressive motility. The couple was counseled to undergo assisted reproduction treatment, but they conceived spontaneously 1 month later. The pregnancy was uneventful, and fetal growth was regular. A spontaneous labor with normal vaginal delivery occurred at full term.
At birth, the male child weighed 3,455 g and was in good health. Postnatal growth was normal. At 1-year follow-up, the development of the child was regular, and the semen analysis of the patient confirmed moderate oligospermia: volume 2.3 mL, sperm count 9 x 106/mL, and 32% progressive motility.

DISCUSSION

To the best of our knowledge, this is the first reported case of a successful full-term pregnancy and live birth in a couple whose male partner had a history of long-term treatment with finasteride. Finasteride (1 mg daily) is widely used for the treatment of men with AGA, many of whom are of reproductive age.
Scant data are available on the effects of finasteride on semen parameters. We have reviewed the literature on finasteride's effects on male fertility and have identified very few randomized studies and some case reports. A doubleblind, placebo-controlled study of 181 healthy men showed that daily treatment with 1 mg of finasteride for 48 weeks did not significantly affect semen parameters.5 Although an early study showed no influence on spermatogenesis in 47 men taking a higher dose of finasteride (5 mg daily),7 a more recent randomized, double-blind, placebo-controlled study of 99 healthy men found that finasteride 5 mg or dutasteride 0.5 mg once daily for 1 year had only mild effects on semen parameters.6 The authors observed a decrease in semen volume, sperm concentration, and sperm motility at the end of treatment, but no change in sperm morphology. At 24-week follow-up, there was nearly complete recovery for total sperm count and semen volume, but not for sperm motility, which was significantly reduced.6 It should be noticed that these randomized studies enrolled only healthy men with no history of infertility or difficulty conceiving5 or those with normal semen parameters.6 Therefore, counseling for men taking finasteride and planning pregnancy is particularly difficult.
Recently, some authors have suggested that in subfertile patients, the negative effects of finasteride therapy might be amplified.8-10 Glina et al8 first reported 3 cases of young patients with very poor semen quality during daily treatment with 1 mg of finasteride. Semen parameters improved considerably after cessation of the drug. Liu et al9 described 2 cases of azoospermia and severe oligospermia in men using 1 mg of finasteride. There was significant improvement in semen parameters and reverse of azoospermia 6 months after the cessation of the finasteride. Another case of azoospermia during treatment with 1 mg of finasteride was described by Chiba et al.10 The patient had been diagnosed with oligospermia 5 years earlier. A significant improvement of semen quality was observed after the discontinuation of finasteride, which allowed the patient to try obtaining pregnancy by intrauterine insemination.
In order to investigate the potential submicroscopic sperm alterations induced by finasteride, Collodel et al11 evaluated sperm morphology by transmission electron microscope, sperm chromosomal abnormalities by fluorescence in situ hybridization and the presence of Y-chromosome microdeletions by polymerase chain reaction in a single patient with azoospermia and in 2 patients with severe asthenozoospermia. Alterations of morphology consistent with necrosis and elevated diploidy and sex chromosome disomy frequencies were found. A significant improvement of semen parameters was observed 1 year after discontinuation of finasteride therapy, whereas the frequency of chromosomal abnormalities was unchanged.
Tu and Zini12 found an elevated sperm DNA fragmentation index (DFI) in a patient receiving 1 mg of finasteride daily who presented for secondary infertility of 4 years' duration. The couple had had 4 consecutive spontaneous abortions. A significant progressive reduction of sperm DFI was observed 3 and 6 months after finasteride discontinuation. The authors