Raloxifene

Beneficial effects of raloxifene and tamoxifen in the treatment of pubertal gynecomastia.

Lawrence SE, Faught KA, Vethamuthu J, Lawson ML.

Source
Department of Pediatrics, University of Ottawa, Ontario, Canada. slawrence@cheo.on.ca

Abstract

OBJECTIVES:
To assess the efficacy of the anti-estrogens tamoxifen and raloxifen in the medical management of persistent pubertal gynecomastia.

STUDY DESIGN:
Retrospective chart review of 38 consecutive patients with persistent pubertal gynecomastia who presented to a pediatric endocrinology clinic. Patients received reassurance alone or a 3- to 9-month course of an estrogen receptor modifier (tamoxifen or raloxifene).

RESULTS:
Mean (SD) age of treated subjects was 14.6 (1.5) years with gynecomastia duration of 28.3 (16.4) months. Mean reduction in breast nodule diameter was 2.1 cm (95% CI 1.7, 2.7, P <.0001) after treatment with tamoxifen and 2.5 cm (95% CI 1.7, 3.3, P <.0001) with raloxifene. Some improvement was seen in 86% of patients receiving tamoxifen and in 91% receiving raloxifene, but a greater proportion had a significant decrease (>50%) with raloxifene (86%) than tamoxifen (41%). No side effects were seen in any patients.

CONCLUSION:
Inhibition of estrogen receptor action in the breast appears to be safe and effective in reducing persistent pubertal gynecomastia, with a better response to raloxifene than to tamoxifen. Further study is required to determine that this is truly a treatment effect.

PMID: 15238910

Pharmacology. 1995 Apr;50(4):209-17.

Antiestrogenic properties of raloxifene.

Draper MW, Flowers DE, Neild JA, Huster WJ, Zerbe RL.

Source

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.

Abstract

This 21-day, open-label study evaluated the effects of raloxifene and tamoxifen on estrogen-induced changes in serum levels of anterior pituitary hormones (prolactin, luteinizing hormone, and follicle-stimulating hormone), sex steroids (testosterone, estradiol), and binding globulins [thyroid binding globulin (T3 resin uptake), transcortin, sex steroid binding globulin]. Seventeen healthy male volunteers completed the study after being randomized to one of three treatments: raloxifene, tamoxifen, or placebo. Six subjects received raloxifene (200 mg daily) for 10 days, 6 subjects received tamoxifen [20 mg twice a day (b.i.d.)] for 10 days, and 5 subjects received placebo for 10 days. All subjects received ethinyl estradiol (20 micrograms b.i.d.) for 7 days starting 3 days after initiation of study drug or placebo treatment. Results of the primary analysis of this study indicate that for six of the seven analyzable parameters of estrogen action (excluding luteinizing hormone) raloxifene blunted the estrogen response; this effect was significant only for T3 resin uptake. Tamoxifen administration significantly blunted or reversed the estrogen effect in all six of these parameters. Raloxifene, an effective antiestrogen in animal models, is also antiestrogenic in humans.

J Endocrinol. 2004 Sep;182(3):399-408.
Raloxifene and hormone replacement therapy increase arachidonic acid and docosahexaenoic acid levels in postmenopausal women.

Giltay EJ, Duschek EJ, Katan MB, Zock PL, Neele SJ, Netelenbos JC.
Source

Psychiatric Center GGZ Delfland, Delft, The Netherlands.

Abstract

Estrogens may affect the essential n-6 and n-3 fatty acids arachidonic acid (AA; C20:4n-6) and docosahexaenoic acid (DHA; C22:6n-3). Therefore, we investigated the long-term effects of hormone replacement therapy and raloxifene, a selective estrogen-receptor modulator, in two randomized, double-blind, placebo-controlled studies. In study I, 95 healthy, non-hysterectomized, early postmenopausal women (age range 47-59 years) received one of the following treatments: daily raloxifene 60 mg (n=24), daily raloxifene 150 mg (n=23), 0.625 mg conjugated equine estrogens (CEE) plus 2.5 mg medroxyprogesterone acetate (MPA; n=24), or placebo (n=24). In study II, 30 men (age range 60-69 years) received daily 120 mg raloxifene (n=15) or placebo (n=15). In study I, plasma cholesteryl ester fatty acids were measured at baseline and after 6, 12, and 24 months in 83 (drop out rate 13%), 73 (23%), and 70 (25%) women respectively. In study II, fatty acids were measured at baseline and after 3 months in 29 men (drop out rate 3%). In postmenopausal women, administration of 150 mg raloxifene increased AA by a mean of +6.1% (P=0.055, not significant). Administration of CEE plus MPA increased AA by +14.1% (P<0.0005). Mean changes in DHA were +22.1% (P=0.003) and +14.9% (P=0.047) respectively, as compared with placebo. In men, 120 mg raloxifene for 3 months did not significantly affect AA (-5.2%; P=0.342) or DHA (+4.0%; P=0.755), but it increased testosterone levels by +19.8% (P=0.006). Administration of raloxifene 150 mg/day as well as CEE plus MPA to postmenopausal women increases the proportion of AA and DHA in plasma cholesteryl esters during a follow-up of 2 years. Short term administration of raloxifene in elderly men did not affect AA or DHA. The synthesis of AA and DHA from precursors may be enhanced through an estrogen receptor-dependent pathway.

Effects of raloxifene on gonadotrophins, sex hormones, bone turnover and lipids in healthy elderly men.

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Eur J Endocrinol. 2004 Apr;150(4):539-46.Duschek EJ, Gooren LJ, Netelenbos C.
Source

Department of Endocrinology, VU University Medical Centre, Amsterdam, The Netherlands. e.duschek@vumc.nl

Abstract

OBJECTIVE:

To explore effects on serum lipids, pituitary-gonadal axis, prostate and bone turnover of the administration of the mixed oestrogen agonist/antagonist raloxifene in healthy elderly men.
PARTICIPANTS:

Thirty healthy men aged 60-70 years randomly received raloxifene 120 mg/day (n=15) or placebo (n=15) for 3 months.
MEASUREMENTS:

In this double-blind, placebo-controlled study, serum gonadotrophins, sex hormones, prostate specific antigen (PSA), a marker of bone turnover, urinary hydroxyproline (OHPro) and cholesterol were measured at baseline and after 3 months.
RESULTS:

Raloxifene significantly increased serum concentrations of LH and FSH (by 29% and 21%), total testosterone (20%), free testosterone (16%) and bioavailable testosterone (not bound to sex hormone-binding globulin (SHBG; 20%). In parallel with testosterone, 17 beta-oestradiol also increased by 21%. SHBG increased by 7%. Total cholesterol (TChol) decreased significantly, from 5.7 to 5.5 mmol/l (P=0.03). Low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) showed a trend to decrease. Overall, there was no change in urinary OHPro/creatinine ratio as a marker for bone resorption. However, the raloxifene-induced increases in both serum testosterone and 17 beta-oestradiol were significantly related to a lower OHPro/creatinine ratio. Total PSA increased by 17% without significant changes in free PSA or free/total PSA ratio. Participants reported no side effects and raloxifene was well tolerated.
CONCLUSION:


In healthy elderly man, raloxifene 120 mg/day for 3 months increased LH, FSH and sex steroid hormones. Potentially beneficial effects were the small but significant decrease in TChol and the trend towards a decrease in LDL-c[COLOR=#000000]. Negative effects were the trend towards a decrease in HDL-c and the significant increase in serum PSA. A decrease in markers of bone resorption during raloxifene treatment was found only in men with relatively high increases in serum testosterone and 17 beta-oestradiol. Overall, there were no clear beneficial effects of administration of raloxifene to ageing men in this preliminary investigation.

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