raloxifene  

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epote
(@epote)
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04/06/2019 10:56 am  

raloxifene taking initiative from the anti-E's topic, here are some abstracts i found casually searching pubmed about raloxifene.

Gonadotrope oestrogen receptor-alpha and -beta and progesterone receptor immunoreactivity after ovariectomy and exposure to oestradiol benzoate, tamoxifen or raloxifene in the rat: correlation with LH secretion.

quote:


Sanchez-Criado JE, de Las Mulas JM, Bellido C, Aguilar R, Garrido-Gracia JC.

Department of Cellular Biology, University of Cordoba, Cordoba, Spain.

The selective oestrogen receptor modulator (SERM) tamoxifen (TX) has agonist/antagonist actions on LH secretion in the rat. Whereas in the absence of oestrogens TX elicits progesterone receptor (PR)-dependent GnRH self-priming, it antagonizes oestrogen-stimulatory action on LH secretion. The aim of these experiments was to explore whether TX treatment-induced differential expression of oestrogen receptor (ER)alpha and ERbeta in the gonadotrope may determine its agonist effect on LH secretion. In the first experiment, basal LH secretion, GnRH-stimulated LH secretion and PR-dependent GnRH self-priming were determined in incubated pituitaries from ovariectomized (OVX) rats treated with oestradiol benzoate (EB), TX or raloxifene (RX). Cycling rats in metoestrus or pro-oestrus were used as basic controls. As in pro-oestrus, pituitaries from OVX rats treated with EB exhibited GnRH-stimulated LH secretion, immunohistochemical PR expression and GnRH self-priming. While RX had no effect on these parameters, TX induced PR expression and GnRH self-priming. GnRH self-priming was absent in pituitaries incubated with the antiprogestin ZK299. In the second experiment, we evaluated the immunohistochemical expression of ERalpha and ERbeta in gonadotropes of cycling rats and OVX rats treated with EB, TX or RX. We found that while ERalpha expression was similar in all six groups, ERalpha expression was oestrous cycle dependent. Moreover, ERalpha expression in gonadotropes of TX-treated rats was as high as that found in pro-oestrus, while ERalpha expression in the gonadotropes of RX-treated rats was lower than in metoestrous or pro-oestrous pituitaries. These results suggest that, in the absence of the cognate ligand, TX, unlike RX, may regulate LH secretion through the ERalpha subtype in gonadotropes.


then again its female rats with no ovaries, so it might as well be completely irelevant

quote:


Effects of clomiphene and raloxifene on gonadotrophin secretion in postmenopausal women: evidence of nongenomic action.

Garas A, Trypsianis G, Kallitsaris A, Milingos S, Messinis IE.

Department of Obstetrics and Gynaecology, University of Thessalia, Medical School, Larissa, Greece.

OBJECTIVE: To evaluate the effect of raloxifene (R) and clomiphene (Cl) on FSH and LH secretion in postmenopausal women. DESIGN: Postmenopausal volunteer women participated in two experimental (Exp) procedures. In Group 1, the women received R (180 mg/day orally) for 30 days plus oestradiol (E2) through skin patches (100 microg/24 h) from days 21 to 30 (R-Exp). After a month's break the same women received Cl (150 mg/day orally) for 30 days plus E2 as above (Cl-Exp). In Group 2, the women received E2 for 30 days plus R from days 21 to 30 (R-Exp) and after a month's break they received E2 for 30 days plus Cl from days 21 to 30 (Cl-Exp). Daily doses were as in Group 1. A GnRH test (100 microg intravenously) was performed in all women on days 0, 10, 20 and 30 of each experiment. PATIENTS: Sixteen healthy postmenopausal women were divided into two groups (eight women in each group). MEASUREMENTS: The area under the curve (AUC) of DeltaFSH and DeltaLH response to GnRH (net increase above the basal value) was calculated. RESULTS: In Group 1, basal levels of FSH and LH did not change significantly during the R-Exp, while they decreased significantly in the Cl-Exp (P < 0.001). The addition of E2 did not have any effect. The AUC of LH response to GnRH increased significantly in the R-Exp (P < 0.05) and that of FSH in the Cl-Exp (P < 0.05). In Group 2, basal levels of FSH and LH declined significantly during treatment with E2 in both the R-Exp (P < 0.01) and the Cl-Exp (P < 0.001). However, the addition of Cl (for 10 days) interrupted this decrease, while the addition of R stimulated FSH levels significantly (P < 0.05). E2 suppressed significantly the AUC of LH in both experiments (P < 0.05). The addition of Cl did not affect the AUC in response to GnRH, while the addition of R increased the AUC of both LH and FSH (P < 0.05). CONCLUSIONS: These results demonstrate for the first time that in contrast to Cl, R does not exert oestrogenic effects on basal gonadotrophin secretion. Although the antioestrogenic action of these drugs was evident only after pretreatment with E2, both R and Cl stimulated GnRH-induced gonadotrophin secretion in oestrogen-deprived women. It is hypothesized that these two compounds sensitize the pituitary to GnRH through mechanisms not involving the oestrogen receptor complex (nongenomic).


but this study, is for estrogen deprived post menupasual women, is this transferable to hypogonadal men? Actually, a little question here, in the abscence of aromatizing agents, after you have HPTA shut down, how does a man produce estrogen? I take it, aromitization isnt the only means in males?

quote:


Raloxifene to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: a randomized controlled trial.

Smith MR, Fallon MA, Lee H, Finkelstein JS.

Division of Hematology and Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

GnRH agonists decrease bone mineral density and increase fracture risk in men with prostate cancer. Raloxifene increases bone mineral density in postmenopausal women, but its efficacy in hypogonadal men is not known. In a 12-month open-label study, men with nonmetastatic prostate cancer (n = 48) who were receiving a GnRH agonist were assigned randomly to raloxifene (60 mg/d) or no raloxifene. Bone mineral densities of the posteroanterior lumbar spine and proximal femur were measured by dual energy x-ray absorptiometry. Mean (+/-se) bone mineral density of the posteroanterior lumbar spine increased by 1.0 +/- 0.9% in men treated with raloxifene and decreased by 1.0 +/- 0.6% in men who did not receive raloxifene (P = 0.07). Bone mineral density of the total hip increased by 1.1 +/- 0.4% in men treated with raloxifene and decreased by 2.6 +/- 0.7% in men who did not receive raloxifene (P < 0.001). Similar between-group differences were observed in the femoral neck (P = 0.06) and trochanter (P < 0.001). In men receiving a GnRH agonist, raloxifene significantly increases bone mineral density of the hip and tends to increase bone mineral density of the spine.


in order to understand this, a GnRH agonist what would do from a systemic stand point? Produce LH? Just bind to the receptor?

quote:


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

Duschek EJ, Gooren LJ, Netelenbos C.

Department of Endocrinology, VU University Medical Centre, Amsterdam, The Netherlands.

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. 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.


i also found a study regarding the fact that raloxifene inhibits IGF but not pulsatile GH (prety much like tamoxifen e i guess) and one regarding leptin

i also found a couple of studies regarding post menopausal women and leptin levels and obesety and how SERMS tend to reverce that which i found nice, but completely irelevant (though i have to say, while i was taking nolva, i kind of lost fat, that i promptly gained back after ceasing)

expand.

p.s sorry if some of the studies are irelevant

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jboldman
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04/06/2019 11:26 am  

The decrease in hdl-c and increase in psa might be a concern.

jb


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ready2explode
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04/06/2019 11:56 am  

TTT

Been searching for new info on RAL and toremifen.

"In any contest between power and patience, bet on patience."
~W.B. Prescott

"Only two things are infinite, the universe and human stupidity, and I'm not sure about the former."
~Albert Einstein


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ready2explode
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04/06/2019 12:15 pm  
Posted by: epote
Effects of raloxifene on gonadotrophins, sex hormones, bone turnover and lipids in healthy elderly men.

Duschek EJ, Gooren LJ, Netelenbos C.

Department of Endocrinology, VU University Medical Centre, Amsterdam, The Netherlands.

This post was modified 6 months ago by Admin

"In any contest between power and patience, bet on patience."
~W.B. Prescott

"Only two things are infinite, the universe and human stupidity, and I'm not sure about the former."
~Albert Einstein


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ready2explode
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04/06/2019 12:45 pm  

Raloxifene treatment is associated with increased serum estradiol and decreased bone remodeling in healthy middle-aged men with low sex hormone levels.

Uebelhart B, Herrmann F, Pavo I, Draper MW, Rizzoli R.

Service of Bone Diseases (WHO Collaborating Center for Osteoporosis Prevention), Department of Rehabilitation and Geriatrics, University Hospital, Geneva 14 CH-1211, Switzerland. Brigitte.Uebelhart@hcuge.ch

In healthy middle-aged men, raloxifene treatment was associated with increased serum estradiol and decreased biochemical markers of bone turnover in subjects with estradiol levels below a threshold of 101.8 pM. INTRODUCTION: We investigated the effects of the selective estrogen receptor modulator raloxifene on bone remodeling in healthy middle-aged men. MATERIALS AND METHODS: Forty-three healthy eugonadal men (mean age, 56 years; range, 49-70 years) were enrolled in a randomized placebo-controlled, double-blind, two-sequence crossover study. The subjects received either raloxifene 120 mg/day or placebo for 6 weeks, followed by a 2-month washout period, before crossing over. To predict changes of urinary total deoxypyridinoline/creatinine on raloxifene treatment, we used a logistic regression model to determine cut-off values of sex hormones for highest sensitivity and specificity. RESULTS: In the whole group, raloxifene treatment was associated with an increase in serum sex hormones, that is, total testosterone (+13%, p < 0.01), bioavailable testosterone (+11%, p = 0.02), total estradiol (+11%, p < 0.002), and bioavailable estradiol (+11%, p = 0.035), and with a decrease in serum osteocalcin (-13%, p < 0.05) and serum total alkaline phosphatase (-6%, p < 0.05). Other biochemical markers of bone turnover remained unchanged. Using a logistic regression model to predict changes in urinary deoxypyridoline, we calculated thresholds for total (101.8 pM) and bioavailable (4.79 pM) estradiol, as well as for total (19.4 nM) and bioavailable (0.35 nM) testosterone. Raloxifene treatment was associated with an increase in serum estradiol and decrease in biochemical markers of bone turnover in men with estradiol values below these estradiol thresholds, without any significant change in subjects with values above them. Similarly, raloxifene treatment was associated with an increase in serum testosterone and a decrease in biochemical markers of bone turnover in those with baseline testosterone values below the testosterone thresholds. The association between antiresorptive effects of raloxifene and low sex hormone levels was more pronounced for estradiol than for testosterone. CONCLUSIONS: The antiresorptive effect of raloxifene was only detectable in men with low baseline estradiol levels. Unlike in postmenopausal women, the increase of estradiol may contribute to the antiresorptive effect of raloxifene in men.

"In any contest between power and patience, bet on patience."
~W.B. Prescott

"Only two things are infinite, the universe and human stupidity, and I'm not sure about the former."
~Albert Einstein


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ready2explode
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04/06/2019 1:04 pm  

Ralox and prostate cancer.

This post was modified 6 months ago by Admin

"In any contest between power and patience, bet on patience."
~W.B. Prescott

"Only two things are infinite, the universe and human stupidity, and I'm not sure about the former."
~Albert Einstein


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Seabiscuit Hogg
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04/06/2019 1:28 pm  

This is not scientific but I used it for pct and it seemed to work quite well. Reminded me of cyclofenil. It's not very easy to suspend tho.

Seabiscuit Hogg is a fictious internet character. It is not recommended that you receive medical advice from fictious internet characters.

SBH :)


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liftsiron
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04/06/2019 1:52 pm  

Some very good reads included in this thread.

liftsiron is a fictional character and should be taken as such.


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