Atherosclerosis 152 2000 159 – 166
Changes in HDL-cholesterol and lipoprotein Lpa after 6-month treatment with finasteride in males affected by benign prostatic
hyperplasia BPH
Licia Denti
a,
, Giuseppe Pasolini
a
, Piero Cortellini
b
, Laura Sanfelici
a
, Raffaella Benedetti
a
, Alessandra Cecchetti
a
, Stefania Ferretti
b
, Lorenza Bruschieri
a
, Fabrizio Ablondi
a
, Giorgio Valenti
a
a
Department of Geriatrics, Cattedra di Gerontologia e Geriatria, Uni6ersita` di Parma, Via Don Bosco
2
,
43100
Parma, Italy
b
Di6isione di Urologia, Azieuda Ospedaliera di Parma, Via Gramsci
14
,
43100
Parma, Italy Received 11 January 1999; received in revised form 7 October 1999; accepted 25 October 1999
Abstract
Androgen effects on lipoproteins, mainly high density lipoprotein HDL, could be exerted by a direct interaction of testosterone T or dihydrotestosterone DHT with liver androgen receptors. To assess if T needs to be converted into DHT to
affect lipid metabolism, 13 patients were studied, affected with benign prostatic hyperplasia BPH and treated with an inhibitor of 5 alpha-reductase finasteride. They were compared with 15 untreated controls. At baseline and after 3 and 6 months of
therapy, each patient was evaluated as for lipoprotein and hormone concentrations, as well as for nutritional status. Body composition was assessed by anthropometry and bio-impedance analysis BIA. Treatment was associated with a significant
increase of HDL-cholesterol HDL-C, mainly HDL3 subclass, and lipoproteina Lpa, as well as a decline of DHT, whereas no significant changes were apparent for T, estradiol E2, sex hormone binding hormone SHBG and body composition indexes.
However, no significant associations between DHT and lipid relative changes were apparent at bivariate correlation analysis. This finding was confirmed by comparing patient subsets identified by cluster analysis, according to HDL subclass individual responses.
Rather, a slight association with E2 for HDL2 positive and HDL3 negative was found. In conclusion, finasteride can modify HDL and Lpa concentrations. However, by the data, these effects cannot be definitively attributed to the changes in DHT
synthesis induced by finasteride, since a direct and non-specific interference of the drug on liver metabolism cannot be excluded. © 2000 Elsevier Science Ireland Ltd. All rights reserved.
Keywords
:
Finasteride; Dihydrotestosterone DHT; High density lipoprotein HDL; Lipoproteina Lpa; Body composition www.elsevier.comlocateatherosclerosis
1. Introduction
A large body of epidemiological data supports a role for male sex as an independent risk factor for cardio-
vascular disease [1]. Factors accounting for the gender- related differences in cardiovascular risk have not yet
been completely elucidated; however, both a protective effect of female sex hormones and an atherosclerosis
promoting effect of male sex hormones have been suggested.
Sex steroids could influence atherogenesis by affect- ing lipoprotein metabolism, as the gender-related differ-
ences in lipid profile clearly suggest [2]. As for androgens, administration of testosterone or similar
compounds [3 – 9] can differently affect lipoproteins, depending on dosages and route of administration.
However, a decrease of high density lipoprotein-choles- terol HDL-C, due to increase in hepatic lipase HL
activity [3,4,8], has been generally found in response to treatment with androgen substances, with variable ef-
fects on low density lipoprotein LDL and very low density lipoprotein VLDL. Furthermore, exogenous
androgens, administered by oral route, can also de- crease the concentrations of lipoprotein a Lpa
Corresponding author. Tel.: + 39-521-236-422; fax: + 39-521- 237-761.
0021-915000 - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 0 2 1 - 9 1 5 0 9 9 0 0 4 4 2 - 6
[10 – 12], a lipoprotein newly recognised as indepen- dently associated with the development of atherosclero-
sis both at coronary and cerebrovascular levels [13 – 15]. Nevertheless, the established effects of exogenous
androgens on HDL and Lpa, have not been defini- tively confirmed for endogenous sex steroids. Indeed,
although an increase of HDL-C and ApoAI has been shown in response to androgen suppression induced by
both orchidectomy or chemical castration [16 – 20], male hypogonadism is not associated with low HDL-C levels
[21]. Also, studies on the correlations between androgen and lipoprotein blood concentrations gave rather confl-
icting results. Indeed, HDL-C has been reported as positively related to testosterone T and dihydrotestos-
terone DHT serum concentrations in man by several studies [22 – 25], although others [26,27] have found no
significant associations. Similarly, no significant associ- ations have been reported between Lpa and androgen
concentrations [28,29], with the exception of a positive correlation
to dehydroepiandrosterone-sulfate
[29]. Therefore, in spite of the abundance of data for the
importance of endogenous testosterone in normal HDL metabolism, its precise role has not yet been clarified.
Besides, it is not clear whether in humans androgen action on lipids is exerted by testosterone itself or, as it
occurs at the level of other androgen targets, by some specific end-products or intermediates in the pathway
of testosterone liver metabolism, such as DHT or estra- diol [30].
The aim of this study was to assess whether in males the inhibition of liver 5 alpha-reductase and, as a
consequence, the decrease in DHT can modify lipo- protein circulating concentrations.
To this purpose, the effects on lipids of finasteride, a 5 alpha-reductase inhibitor, recently introduced as
treatment of benign prostatic hyperplasia BPH were studied [31].
2. Materials and methods
