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Research Letter |

Androgen Levels and Semen Parameters Among Former Users of Finasteride With Persistent Sexual Adverse Effects FREE

Michael S. Irwig, MD1
[+] Author Affiliations
1Division of Endocrinology and Center for Andrology, The George Washington University, Washington, DC
JAMA Dermatol. 2014;150(12):1361-1363. doi:10.1001/jamadermatol.2014.1830.
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Published online

Recent postmarketing studies and the US Food and Drug Administration have found that finasteride, 1 mg, for androgenic alopecia has been associated with persistent sexual and nonsexual adverse effects.1 The mechanisms of these symptoms in humans are unknown. Finasteride, 1 mg, has been associated with male infertility, and 5% of men taking a 5α-reductase inhibitor had a dramatic decline in total sperm count to below 10% of baseline.2,3 The present study was designed to assess whether otherwise healthy former users of finasteride with persistent sexual adverse effects have a higher prevalence of low serum androgens and spermatogenic deficits compared with reference populations.

This study was approved by the George Washington University institutional review board, and all participants provided their written informed consent.

Participants (n = 24) were otherwise healthy young men who developed persistent sexual adverse effects associated with finasteride use (≤1.00-1.25 mg/d) for androgenic alopecia. The exclusion criteria were a history of any chronic medical condition, a current or past psychiatric condition, a history of taking nontopical medications other than antibiotics prior to finasteride, an abnormal baseline sexual function, or medication use in the previous 3 months that could affect androgens or fertility.

As previously described,1 participants were administered standardized interviews that included the use of a validated instrument to assess sexual function. Participants were recruited via the author’s practice and through an internet forum (www.propeciahelp.com). To minimize intraindividual variability, participants were asked to obtain 2 sets of morning androgen measurements (testosterone and dihydrotestosterone [DHT]), and semen analyses were performed at least 1 month apart.

Clinical characteristics and serum androgen levels are listed in Table 1. Two measurements of total testosterone and DHT levels were available for 20 (83%) and 18 (75%) participants, respectively. Two confirmed low total testosterone and DHT levels were found in 3 (13%) and 3 (13%) participants, respectively. Two of 23 participants (9%) had 2 confirmed low levels of both androgens.

Table Graphic Jump LocationTable 1.  Participant Characteristics, Finasteride Use, Sexual Function, and Androgen Levels

Ten participants (42%) provided 2 semen analyses, and 9 participants (38%) provided 1 (Table 2). The mean (SD) and median sperm concentrations were 70 (70) and 60 million/mL, respectively, with 3 of 19 participants (16%) having severe oligospermia (<5 million/mL). The mean (SD) and median motilities were 50% (23%) and 50%, respectively, with 4 of 9 participants (44%) having 2 confirmed low motility values. Four of 8 participants (50%) had 2 confirmed low morphology values. The mean (SD) and median volumes were 2.9 mL (1.0 mL) and 2.7 mL, respectively.

Low serum androgen levels at the time of the study cannot explain the persistent sexual adverse effects because mean levels were similar to those in other studies. Nonetheless, the prevalence of confirmed low androgen levels (13%) is higher than the expected 5% according to the reference ranges for the assays. When the semen parameter results were compared with those from a general population of unscreened men from a World Health Organization study,4 the median semen volume was between the 25th and 50th percentiles, and the total motility was between the 10th and 25th percentiles. Although the median sperm concentration was similar to that found in other studies, 16% (3 of 19) had severe oligospermia. For comparison, only 3% of fertile men have a sperm concentration under 10 million/mL.5

Limitations of this postmarketing study include lack of baseline androgen levels and semen parameters, selection bias, missing data, and small sample size. Another limitation is that serum androgen levels often do not reflect tissue levels. One study of men with persistent effects of finasteride found lower cerebrospinal fluid concentrations of DHT, allopregnanolone, and isopregnanolone and higher levels of testosterone and estradiol.6 Further research is needed on the subset of men who may be susceptible to 5α-reductase inhibitors.

Accepted for Publication: June 10, 2014.

Corresponding Author: Michael S. Irwig, MD, Division of Endocrinology, Medical Faculty Associates and George Washington University, 2150 Pennsylvania Ave NW, Washington, DC 20037 (mirwig@mfa.gwu.edu).

Published Online: September 17, 2014. doi:10.1001/jamadermatol.2014.1830.

Conflict of Interest Disclosures: None reported.

Additional Contributions: I thank Richard Amdur, PhD, for the statistical analysis, and I thank the study participants for their time.

Irwig  MS, Kolukula  S.  Persistent sexual side effects of finasteride for male pattern hair loss. J Sex Med. 2011;8(6):1747-1753.
PubMed   |  Link to Article
Samplaski  MK, Lo  K, Grober  E, Jarvi  K.  Finasteride use in the male infertility population: effects on semen and hormone parameters. Fertil Steril. 2013;100(6):1542-1546.
PubMed   |  Link to Article
Amory  JK, Wang  C, Swerdloff  RS,  et al.  The effect of 5alpha-reductase inhibition with dutasteride and finasteride on semen parameters and serum hormones in healthy men. J Clin Endocrinol Metab. 2007;92(5):1659-1665.
PubMed   |  Link to Article
Cooper  TG, Noonan  E, von Eckardstein  S,  et al.  World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16(3):231-245.
PubMed   |  Link to Article
Guzick  DS, Overstreet  JW, Factor-Litvak  P,  et al; National Cooperative Reproductive Medicine Network.  Sperm morphology, motility, and concentration in fertile and infertile men. N Engl J Med. 2001;345(19):1388-1393.
PubMed   |  Link to Article
Melcangi  RC, Caruso  D, Abbiati  F,  et al.  Neuroactive steroid levels are modified in cerebrospinal fluid and plasma of post-finasteride patients showing persistent sexual side effects and anxious/depressive symptomatology. J Sex Med. 2013;10(10):2598-2603.
PubMed

Figures

Tables

Table Graphic Jump LocationTable 1.  Participant Characteristics, Finasteride Use, Sexual Function, and Androgen Levels

References

Irwig  MS, Kolukula  S.  Persistent sexual side effects of finasteride for male pattern hair loss. J Sex Med. 2011;8(6):1747-1753.
PubMed   |  Link to Article
Samplaski  MK, Lo  K, Grober  E, Jarvi  K.  Finasteride use in the male infertility population: effects on semen and hormone parameters. Fertil Steril. 2013;100(6):1542-1546.
PubMed   |  Link to Article
Amory  JK, Wang  C, Swerdloff  RS,  et al.  The effect of 5alpha-reductase inhibition with dutasteride and finasteride on semen parameters and serum hormones in healthy men. J Clin Endocrinol Metab. 2007;92(5):1659-1665.
PubMed   |  Link to Article
Cooper  TG, Noonan  E, von Eckardstein  S,  et al.  World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16(3):231-245.
PubMed   |  Link to Article
Guzick  DS, Overstreet  JW, Factor-Litvak  P,  et al; National Cooperative Reproductive Medicine Network.  Sperm morphology, motility, and concentration in fertile and infertile men. N Engl J Med. 2001;345(19):1388-1393.
PubMed   |  Link to Article
Melcangi  RC, Caruso  D, Abbiati  F,  et al.  Neuroactive steroid levels are modified in cerebrospinal fluid and plasma of post-finasteride patients showing persistent sexual side effects and anxious/depressive symptomatology. J Sex Med. 2013;10(10):2598-2603.
PubMed

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