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Androlog Summary |
From the Northwestern University Feinberg School of Medicine, Department of Urology, Chicago, Illinois.
| Received for publication September 22, 2009; accepted for publication October 2, 2009. |
The first posting came from Dr Mark Jutras (United States) who wrote:
Have my first patient requesting information on the possibility of Propecia/finasteride interfering with fertility. Reading the PDR is surprisingly uninformative. It would have been easy to do human studies but none are quoted. I find it hard to believe that this was not required before the release. My understanding of the mechanism of action would suggest that it should interfere with male fertility (I am not interested in the rabbit and rat studies). Is there any useful information one way or the other?
In response, Dr Terry Turner (United States) echoed the above concerns when he wrote:
I am not an expert on this, but it seems to me the information on human males is pretty light. I recall a study where human male ejaculate sperm concentration was not reduced by finasteride (I don't remember dose or duration). Presented almost as an aside was the information that ejaculate volume was reduced. The tone of the report was that this meant there should be no effects on fertility. It seemed strange to me that no comment was made about the reasonable conclusion that if ejaculate volume is reduced and sperm concentration stays the same, this means that testicular output of sperm must be reduced. This should at least cause some concern, no? Of course, it is difficult to do experiments in humans. Perhaps if there was more interest in the rat and rabbit data...
Dr Nancy Brackett (United States) offered an answer to the question:
See: Overstreet et al, Chronic treatment with finasteride daily does not affect spermatogenesis or semen production in young men. J Urol. 1999;162:1295–1300.With finasteride, there were no significant effects on sperm concentration, total sperm per ejaculate, sperm motility, or morphology. There was decreased ejaculate volume, prostate volume, and serum PSA with finasteride. No fertilization or pregnancy data are given.
The above study is a randomized, double-blind, placebo-controlled, multicenter trial in which the dose of finasteride was 1 mg. The results show that spermatogenesis was not adversely affected by the drug. Although no pregnancy data were given, it is reasonable to assume that 1 mg of finasteride does not cause male factor infertility. However, it should be noted that the above study only applies to the 1-mg dose. A study by Amory et al (2007) suggested that 5 mg of finasteride or 0.5 mg of dutasteride mildly decreases semen parameters. Although, this finding appears controversial, in that Lewis et al (1992) found no effect on spermatogenesis in 47 men taking 5 mg of finasteride.
In addition to concerns over finasteride's effect on spermatogenesis, there have also been concerns about a male partner taking finasteride during pregnancy. Lynn Collins (United States) raised this concern when she wrote:
The package insert for Propecia states that pregnant women should not touch the pill, may cause abnormalities to the genitalia of the male fetus.
Dr Stewart McCallum (United States) then replied, quoting 2 studies by Merck in which the levels of finasteride were measured in the semen of men taking 5 mg of the drug:
Regarding the use of finasteride in men whose partners may be pregnant: It is a standard requirement for the FDA to ask for dedicated studies to look at drug concentrations found in semen. Merck performed 2 such studies, and the following is taken from the prescribing information. In 2 studies of healthy subjects (n = 69) receiving PROSCAR 5 mg/d for 6–24 weeks, finasteride concentrations in semen ranged from undetectable (<0.1 ng/mL) to 10.54 ng/mL. In an earlier study using a less sensitive assay, finasteride concentrations in the semen of 16 subjects receiving PROSCAR 5 mg/d ranged from undetectable (<1.0 ng/mL) to 21 ng/mL. Thus, based on a 5-mL ejaculate volume, the amount of finasteride in semen was estimated to be 50- to 100-fold less than the dose of finasteride (5 =µg) that had no effect on circulating DHT levels in men (see also PRECAUTIONS, Pregnancy). So the quantities of drug in the semen are 50- to 100-fold less than doses in serum which have been shown to have no effect on circulating DHT, and this is assuming that 100% of the of the finasteride present in the semen is absorbed by the female partner (which has not been confirmed). So the next question one would need to address is whether 50- to 100-fold coverage below doses that had no effect on circulation DHT is adequate. This is the risk benefit question that you need to address with your patient.
Although the above comments reference 2 studies using a 5-mg dose, Merck (2007) also measured semen levels of finasteride in patients taking a 1-mg dose. The men were treated with 1 mg for 6 weeks. The highest level measured was 1.52 ng/mL, and the mean level was 0.26 ng/mL. Using the highest measured level (1.52 ng/mL), women exposed to a 5-mL ejaculate per day would be exposed to 7.6 ng/d (assuming 100% vaginal absorption). Merck (2007) found this level to be 750 times lower than the "no effect" level for developmental abnormalities in rhesus monkeys.
In summary, a 1-mg dose of finasteride does not appear to adversely affect spermatogenesis. In addition, the level present in the ejaculate of patients taking 1 mg appears to be negligible. Thus, there does not appear to be any need to stop 1 mg of finasteride in those patients trying to conceive or in those whose partners are pregnant.
Footnotes
Note: Postings to Androlog have been lightly edited before publication.
References
Amory J, Wang C, Swerdloff R, Anawalt B, Matsumoto A, Bremner W,
Walker S, Haberer L, Clark R. The effect of 5
-reductase inhibition with
dutasteride and finasteride on semen parameters and serum hormones in healthy
men. J Clin Endocrinol Metab. 2007; 92: 1659
–1665.
Lewis RW, Lieber MM, Hellstrom WJ, et al. The effect of finasteride on semen production and sexual function in normal males. J Urol. 1992;147: 398A ..
Merck and Co, Inc, PROPECIA® (Finasteride) Tablets, 1 mg, Product Insert. Issued May 2007 . Distributed by Merck and Co, Inc, Whitehouse Station, NJ 08889, USA.
Overstreet J, Fuh V, Gould J, Howards S, Liever M, Hellstrom W, Shapiro S, Carroll P, Corfman R, Petrou S, Lewis R, Toth P, Shown T, Roy J, Jarow J, Bonilla J, Jacobsen C, Wang D, Kaufman K. Chronic treatment with finasteride daily does not affect spermatogenesis or semen production in young men. J Urol. 1999; 162: 1295 –1300.[CrossRef][Medline]
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