Απ: finasteride και γονιμοτητα.
Published-Ahead-of-Print on October 15, 2009 by Journal of Andrologys
Androlog Summary: Effect of 1 mg dose of Finasteride on Spermatogenesis
and Pregnancy
Eric LaBorde, MD1 and Robert E. Brannigan, MD1
1Northwestern University Feinberg School of Medicine, Department of Urology, Chicago, IL
The effect of finasteride on spermatogenesis and its use by male partners during pregnancy is a
topic that has garnered interest recently. While finasteride has been approved to treat BPH since
1992, a 1 mg dose has been used to treat male pattern baldness since 1997. This newer treatment
indication has resulted in far more men who are of reproductive age using the drug. This has
caused some to consider finasteride’s effect on both fertility and pregnancy as the below string of
Androlog entries highlights.
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,
Published-Ahead-of-Print on October 15, 2009 by Journal of Andrology
Copyright 2009 by The American Society of Andrology
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 as 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 two such studies, and the following is taken from the
prescribing information.
In 2 studies of healthy subjects (n=69) receiving PROSCAR 5 mg/day 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/day 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.
While the above comments reference two 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 six 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 a 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 5α-Reductase Inhibition with Dutasteride and Finasteride on Semen
Parameters and Serum Hormones in Healthy Men. The Journal of Clinical Endocrinology &
Metabolism. 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. Journal of Urology 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. Journal of Urology 1999;162:1295-1300.
