Sehr geehrter Lars,
anbei die derzeit verfügbare Literatur zu dem von Ihnen angesprochenem Thema mit anschließender Interpretation von Professor Wolff und mir.
1: J Clin Endocrinol Metab. 2007 May;92(5):1659-65.
The effect of 5alpha-reductase inhibition with dutasteride and finasteride on semen parameters and serum hormones in healthy men.
Amory JK, Wang C, Swerdloff RS, Anawalt BD, Matsumoto AM, Bremner WJ, Walker SE, Haberer LJ, Clark RV.
CONTEXT: Dutasteride and finasteride are 5alpha-reductase inhibitors (5ARIs) that dramatically reduce serum levels of dihydrotestosterone (DHT). OBJECTIVE: Because androgens are essential for fertility, we sought to determine the impact of 5ARI administration on serum testosterone (T), DHT, and spermatogenesis.
DESIGN, SETTING, SUBJECTS, AND INTERVENTION: We conducted a randomized, double-blinded, placebo-controlled trial in 99 healthy men randomly assigned to receive dutasteride (D; 0.5 mg) (n = 33), finasteride (F; 5 mg) (n = 34), or placebo (n = 32) once daily for 1 yr.
MAIN OUTCOME MEASURES: Blood and semen samples were collected at baseline and 26 and 52 wk of treatment and 24 wk after treatment and were assessed for T, DHT, and semen parameters.
RESULTS: D and F significantly (P < 0.001) suppressed serum DHT, compared with placebo (D, 94%; F, 73%) and transiently increased serum T. In both treatment groups, total sperm count, compared with baseline, was significantly decreased at 26 wk (D, -28.6%; F, -34.3%) but not at 52 wk (D, -24.9%; F, -16.2%) or the 24-wk follow-up (D, -23.3%; F, -6.2%). At 52 wk, semen volume was decreased (D, -29.7%; F, -14.5%, significantly for D) as was sperm concentration (D, -3.2%; [corrected] F, -7.4%, neither significant). There was a significant reduction of -6 to 12% in sperm motility during treatment with both D and F and at follow-up. Neither treatment had any effect on sperm morphology.
CONCLUSIONS: This study demonstrates that the decrease in DHT induced by 5ARIs is associated with mild decreases in semen parameters that appear reversible after discontinuation.
2: Fertil Steril. 2008 Sep;90(3):849.e17-9.
Propecia-induced spermatogenic failure: a report of two cases.
Liu KE, Binsaleh S, Lo KC, Jarvi K.
OBJECTIVE: To describe the results of two cases of azoospermia and severe oligospermia in men during and after cessation of finasteride 1 mg.
DESIGN: Case report.
SETTING: Tertiary-care hospital-based clinic for andrology/male infertility.
PATIENT(S): Two patients with azoospermia and severe oligospermia using finasteride 1 mg for hair loss.
INTERVENTION(S): Discontinuation of finasteride.
MAIN OUTCOME MEASURE(S): Improvement in sperm concentration.
RESULT(S): Patient A had documented azoospermia over 1 year and was initially booked for a testicular biopsy. Six months after discontinuation of finasteride 1 mg daily he showed improvement in sperm concentration to 5.5 x 10(6)/mL. Patient B had severe oligospermia with a sperm concentration of 4 x 10(6)/mL. Sperm concentration improved to 6.6 then 18.7 x 10(6)/mL at 3 and 6 months after stopping finasteride.
CONCLUSION(S): We report two cases of infertile patients with azoospermia or severe oligospermia who showed significant improvements in sperm concentrations 6 months after the discontinuation of finasteride. In one case, improvement in semen parameters prevented the need for testicular biopsy and corrected the azoospermia. Stopping finasteride in the infertility population may improve semen parameters, and may allow for less invasive fertility treatments.
3. Arch Androl. 2007 Jul-Aug;53(4):229-33.
Spermatozoa and chronic treatment with finasteride: a TEM and FISH study.
Collodel G, Scapigliati G, Moretti E.
Finasteride is a specific inhibitor of the 5alpha reductase enzyme originally approved for the treatment of benign prostatic hypertrophy and also for the treatment of androgenetic alopecia (AGA) in men at a dose of 1 mg/day. We report on three cases of young men recruited at our Centre for Male Infertility who had used finasteride for five years. Semen quality was investigated by light microscopy to evaluate sperm concentration and motility. Sperm morphology was performed by transmission electron microscope (TEM) and the data were analyzed. The presence of Y microdeletions was investigated by PCR. Meiotic segregation was explored by fluorescence in situ hybridization (FISH). Patient 1 was azoospermic, patients 2 and 3 showed a normal sperm concentration and severely reduced progressive motility. TEM analysis revealed altered sperm morphology consistent with necrosis and FISH data revealed elevated diploidy and sex chromosome disomy frequencies. This examination was repeated 1 year after the men had suspended the use of finasteride, without receiving any other treatment. A recovery of spermatogenetic process was observed. Motility and morphology improved whereas the meiotic pattern did not change presenting elevated diploidy and sex chromosome disomy frequency.
Die 2 Fallberichte (Literaturstellen 2 und 3) sind wissenschaftlich völlig insuffizient.
Bei jeder Negativ-Selektion (Azoo- oder Oligozoospermie als Auswahlkriterium) hat jede weitere Kontrolluntersuchung eine erhöhte Wahrscheinlichkeit eines verbesserten Befundes. Das Phänomen heißt "Regression towards the Mean".
Mit diesen insuffizienten Methoden könnte man wahrscheinlich genauso gut Männer finden, deren Spermiogramme sich nach Absetzen von Finasterid verschlechtert haben.
Die erste Studie (Literaturstelle 1) krankt schon mal daran, dass üblicherweise 2 Baseline-Spermiogramme gefordert werden. Auch ist das Risiko eines Sampling-Errors bei nur 33 Teilnehmern pro Gruppe relativ hoch.
Also Fazit: Keine Beweise, aber bei Kinderwunsch (unerfüllt) und ungünstigen Spermiogrammparametern des Mannes ggf doch vorsichtshalber Finasterid absetzen, und auf Minoxidi umsetzen.
Anbei noch die Publikation aus dem Jahr 1999, die zeigen konnten, dass im Rahmen einer Studie die Spermiogenese durch Propecia nicht beeinflusst wurden.
J Urol. 1999 Oct;162(4):1295-300.
Chronic treatment with finasteride daily does not affect spermatogenesis or semen production in young men.
Overstreet JW, Fuh VL, Gould J, Howards SS, Lieber MM, Hellstrom W, Shapiro S, Carroll P, Corfman RS, Petrou S, Lewis R, Toth P, Shown T, Roy J, Jarow JP, Bonilla J, Jacobsen CA, Wang DZ, Kaufman KD.
PURPOSE: Finasteride, an oral type 2, 5alpha-reductase inhibitor, is used in 1 mg. daily doses for the treatment of male pattern hair loss. A dose of 5 mg. finasteride daily reduces ejaculate volume by approximately 25%, and reduces prostate volume by approximately 20% and serum prostate specific antigen (PSA) by approximately 50% in men with benign prostatic hyperplasia. To our knowledge no data exist on the effect of 1 mg. finasteride daily on ejaculate volume or other semen parameters, or on the prostate in young men. Therefore, we studied the potential effect and reversibility of effect of 1 mg. finasteride daily on spermatogenesis, semen production, the prostate and serum PSA in young men.
MATERIALS AND METHODS: In this double-blind, placebo controlled multicenter study 181 men 19 to 41 years old were randomized to receive 1 mg. finasteride or placebo for 48 weeks followed by a 60-week off-drug period. Of the 181 men 79 were included in a subset for the collection and analysis of sequential semen samples.
RESULTS: There were no significant effects of 1 mg. finasteride on sperm concentration, total sperm per ejaculate, sperm motility or morphology. Ejaculate volume in subjects on finasteride decreased 0.3 ml. (-11%) compared to a decrease of 0.2 ml. (-8%) for placebo, with a median between treatment group difference of -0.03 ml. (1%, 90% confidence interval -10.4 to 13.1, p = 0.915). There were significant but small decreases in prostate volume (-2.6%) and serum PSA (-0.2 ng./ml.) in the finasteride group, which reversed on discontinuation of the drug.
CONCLUSIONS: Treatment with 1 mg. finasteride daily for 48 weeks did not affect spermatogenesis or semen production in young men. The effects of 1 mg. finasteride daily on prostate volume and serum PSA in young men without benign prostatic hyperplasia were small and reversible on discontinuation of the drug.
Dr. C. Kunte |
