Ipriflavone prevents the bone mass reduction in premenopausal women treated with gonadotropin hormone-releasing hormone agonists

Gambacciani, Marco; Spinetti, A.; Piaggesi, Laura; Cappagli, Barbara; Taponeco, Fabio; Manetti, Pietro; Weiss, Carlo; Teti, G; Commare, Paolo La; Facchini, V.

doi:10.1016/s0169-6009(08)80159-6

Cited by 32 publications

(11 citation statements)

References 29 publications

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“…Only Studd and Leather [18] (2 mg 17ß-estradiol valerate plus 5 mg norethisterone acetate) reported almost full prevention of bone mineral loss Gnoth/Gödtke/Freundl/Godehardt/Kienle with some evidence of reduced GnRHa efficacy in patients treated with GnRHa for premenstrual syndrome. All available studies clearly show the accelerated loss in BMD with GnRHa monotherapy [19][20][21][22]. The loss ranges from 5 to 9%, which is similar to our findings.…”

Section: Discussionsupporting

confidence: 90%

Effects of Add-Back Therapy on Bone Mineral Density and Pyridinium Crosslinks in Patients with Endometriosis Treated with Gonadotropin-Releasing Hormone Agonists

Gnoth

Gödtke

Freundl

et al. 1999

Gynecol Obstet Invest

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Treatment of endometriosis with gonadotropin-releasing hormone agonists (GnRHa) is limited to 6 months because of possible adverse effects on bone metabolism. We designed a randomized, double-blind, placebo-controlled, prospective study of 27 patients with endometriosis who were given GnRHa with or without hormone add-back therapy (+ 20 µg of ethinyl estradiol with 0.15 mg desogestrel) designed to suppress the adverse effects of hypoestrogenism while preserving the efficacy of GnRHa. Both regimens showed significant improvements in endometriosis, dysmenorrhea, and pelvic pain; effects were significantly better in the GnRHa + placebo group. The GnRHa + placebo group had significantly higher serum calcium levels and a significantly higher loss of lumbar spine bone mineral density (BMD). Urinary levels of pyridinium crosslinks increased significantly in the GnRHa + placebo group, and declined to normal in the GnRHa + add-back group. The add-back therapy protects women taking GnRHas from severe loss of BMD and accelerated bone collagen resorption, but reduces the efficacy of the GnRHa.

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Section: Discussionsupporting

confidence: 90%

Effects of Add-Back Therapy on Bone Mineral Density and Pyridinium Crosslinks in Patients with Endometriosis Treated with Gonadotropin-Releasing Hormone Agonists

Gnoth

Gödtke

Freundl

et al. 1999

Gynecol Obstet Invest

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“…Ipriflavone, (IPR; 7-isopropoxyisoflavone), an isoflavone derivative, has been the phytoestrogen most studied as a therapeutic agent in osteoporosis. Daily oral doses of 3-10 mg/kg/day IPR prevent bone turnover and loss in bone density in women who are postmenopausal or who have been treated with gonadotropinreleasing hormone (GnRH) agonists (132)(133)(134). These doses produce plasma concentrations (135) similar to the in vitro concentrations (≥ 100 nM) required for inhibition of osteoclast differentiation (136) and bone resorption (137).…”

Section: Bone Densitymentioning

confidence: 99%

Cross-species and interassay comparisons of phytoestrogen action.

Whitten

Patisaul

2001

Environ Health Perspect

171

105

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This paper compiles animal and human data on the biologic effects and exposure levels of phytoestrogens in order to identify areas of research in which direct species comparisons can be made. In vitro and in vivo assays of phytoestrogen action and potency are reviewed and compared to actions, dose-response relationships, and estimates of exposure in human subjects. Binding studies show that the isoflavonoid phytoestrogens are high-affinity ligands for estrogen receptors (ERs), especially ER beta, but have lower potency in whole-cell assays, perhaps because of interactions with binding proteins. Many other enzymatic actions require concentrations higher than those normally seen in plasma. In vivo data show that phytoestrogens have a wide range of biologic effects at doses and plasma concentrations seen with normal human diets. Significant in vivoresponses have been observed in animal and human tests for bone, breast, ovary, pituitary, vasculature, prostate, and serum lipids. The doses reported to be biologically active in humans (0.4--10 mg/kg body weight/day) are lower than the doses generally reported to be active in rodents (10--100 mg/kg body weight/day), although some studies have reported rodent responses at lower doses. However, available estimates of bioavailability and peak plasma levels in rodents and humans are more similar. Steroidogenesis and the hypothalamic-pituitary-gonadal axis appear to be important loci of phytoestrogen actions, but these inferences must be tentative because good dose-response data are not available for many end points. The similarity of reported proliferative and antiproliferative doses illustrates the need for fuller examination of dose-response relationships and multiple end points in assessing phytoestrogen actions.

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“…In some countries, it has been marketed as a nonhormonal treatment for osteoporosis in those women who cannot receive hormone replacement therapy (Zsuzsanna, 1995). Its use has also been reported for the prevention of rapid bone loss that occurs following induction of hypogonadism in premenopausal women treated with gonadotrophin hormone-releasing hormone agonists (Gambacciani et al, 1994). Interestingly, one of the main metabolites of ipriflavone in humans is daidzein, which constitutes approximately 10 % of all its metabolites (Brandi, 1992).…”

Section: Osteoporosismentioning

confidence: 99%

Phytoestrogens and human health effects: weighing up the current evidence

Humfrey¹

1998

Nat. Toxins

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Ipriflavone prevents the bone mass reduction in premenopausal women treated with gonadotropin hormone-releasing hormone agonists

Cited by 32 publications

References 29 publications

Effects of Add-Back Therapy on Bone Mineral Density and Pyridinium Crosslinks in Patients with Endometriosis Treated with Gonadotropin-Releasing Hormone Agonists

Effects of Add-Back Therapy on Bone Mineral Density and Pyridinium Crosslinks in Patients with Endometriosis Treated with Gonadotropin-Releasing Hormone Agonists

Cross-species and interassay comparisons of phytoestrogen action.

Phytoestrogens and human health effects: weighing up the current evidence

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