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Lack of any estrogenic effect of ipriflavone in postmenopausal women

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Abstract

Estrogen replacement therapy (ERT) has been demonstrated to prevent osteoporosis in postmenopausal women (PMW). However, several contraindications exist for ERT and many PMW cannot be treated. It has also been shown that too low doses of ERT are able to exert therapeutical effects on some climacteric symptoms but not on bone and compounds exerting synergic actions with ERT on bone without effects on other organs could be useful. The isoflavone derivative, ipriflavone, seems to have this effect but data are lacking on its endocrine effect in humans; thus, this study was undertaken to clarify in PMW whether ipriflavone exerts estrogenic activity. Evaluation of LH and FSH secretion during a 24-h period was performed in a group of 15 PMW after a single oral dose of 600 or 1,000 mg of ipriflavone or placebo, and after 7, 14 and 21 days of oral treatment with ipriflavone 600 mg and 1,000 mg/daily, administered in three divided doses. LH secretion was also evaluated during naloxone infusion before and after 21 days of ipriflavone, placebo or conjugated estrogen treatment (0.625 mg/day; CE). LH response to NAL treatment was absent during ipriflavone and placebo such as it was observed before treatments. By contrast, a significant increase of LH plasma levels was measured during naloxone infusion in CE-treated women. This result demonstrates that ipriflavone is unable to exert the same effects that estrogens do in PMW. In addition, no changes like in placebo group were seen on vaginal cytology in this group of subjects after 21 days, whereas a significant increase of superficial vaginal cells was observed after 21 days of CE treatment. These data confirm that ipriflavone is devoid of estrogenic activity also in humans and its efficacy in the prevention of osteoporosis in PMW should be ascribed to different mechanisms of action in comparison to estrogens.

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Authors and Affiliations

  1. Direttore dell’Istituto di Ginecologia Ostetricia e Fisiopatologia della Riproduzione Umana, University of Cagliari, Via Ospedale 46, 09124, Cagliari, Italy

    Gian Benedetto Melis, A. M. Paoletti & A. Cagnacci

  2. Istituto di Clinica Ginecologica ed Ostetrica, University of Pisa, Parma, Italy

    A. Spinetti, M. Gambacciani & P. Fioretti

  3. Dipartimento Ricerche Farmacologiche, Chiesi Farmaceutici, Parma, Italy

    L. Bufalino

Authors
  1. Gian Benedetto Melis
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  2. A. M. Paoletti
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  3. A. Cagnacci
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  4. L. Bufalino
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  5. A. Spinetti
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  6. M. Gambacciani
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  7. P. Fioretti
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Melis, G.B., Paoletti, A.M., Cagnacci, A. et al. Lack of any estrogenic effect of ipriflavone in postmenopausal women. J Endocrinol Invest 15, 755–761 (1992). https://doi.org/10.1007/BF03347647

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  • DOI: https://doi.org/10.1007/BF03347647

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