Brain-Selective Estrogen Therapy Prevents Androgen Deprivation-Associated Hot Flushes in a Rat Model.

Pharmaceuticals
Istvan MerchenthalerLaszlo Prokai

Abstract

Hot flushes are best-known for affecting menopausal women, but men who undergo life-saving castration due to androgen-sensitive prostate cancer also suffer from these vasomotor symptoms. Estrogen deficiency in these patients is a direct consequence of androgen deprivation, because estrogens (notably 17β-estradiol, E2) are produced from testosterone. Although estrogens alleviate hot flushes in these patients, they also cause adverse systemic side effects. Because only estrogens can provide mitigation of hot flushes on the basis of current clinical practices, there is an unmet need for an effective and safe pharmacotherapeutic intervention that would also greatly enhance patient adherence. To this end, we evaluated treatment of orchidectomized (ORDX) rats with 10β, 17β-dihydroxyestra-1,4-dien-3-one (DHED), a brain-selective bioprecursor prodrug of E2. A pilot pharmacokinetic study using oral administration of DHED to these animals revealed the formation of E2 in the brain without the appearance of the hormone in the circulation. Therefore, DHED treatment alleviated androgen deprivation-associated hot flushes without peripheral impact in the ORDX rat model. Concomitantly, we showed that DHED-derived E2 induced progesterone recepto...Continue Reading

References

Oct 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·L M KaplanW W Chin
Dec 1, 1984·The Journal of Clinical Endocrinology and Metabolism·J JelinekP Lomax
Jan 9, 1999·Maturitas·I MerchenthalerR C Winneker
Jun 17, 2000·Trends in Endocrinology and Metabolism : TEM·E SimpsonS Davis
Jun 16, 2001·American Journal of Human Biology : the Official Journal of the Human Biology Council·R R Freedman
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jan 25, 2003·Menopause : the Journal of the North American Menopause Society·Anna-Clara E SpetzMats L Hammar
Jun 11, 2009·Menopause : the Journal of the North American Menopause Society·Asher J Albertson, Donal C Skinner
Jun 23, 2011·Reproductive Biology and Endocrinology : RB&E·Willem de Ronde, Frank H de Jong
Sep 5, 2014·International Journal of Urology : Official Journal of the Japanese Urological Association·Alessandro SciarraStefano Salciccia
Apr 9, 2015·Breast Cancer Research and Treatment·Flora ZagouriTheodora Psaltopoulou
Jul 24, 2015·Science Translational Medicine·Laszlo ProkaiKatalin Prokai-Tatrai
Sep 1, 2015·Endocrinology and Metabolism Clinics of North America·Nanette SantoroSarah B Mathews
Jun 15, 2016·The Journal of Clinical Endocrinology and Metabolism·Alexander P TaylorJoel S Finkelstein
Apr 6, 2017·Climacteric : the Journal of the International Menopause Society·D W SturdeeM A Lumsden
May 26, 2017·Physiological Reviews·Paul S CookeRex A Hess
May 17, 2019·European Journal of Endocrinology·Nicholas Russell, Mathis Grossmann
Nov 23, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Katalin Prokai-Tatrai, Laszlo Prokai
May 21, 2020·Pharmaceutics·Katalin Prokai-TatraiLaszlo Prokai

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Nov 23, 2020·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Nidheesh ThadathilMohammad Moshahid Khan

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