Browsing by Subject "Estrogens / administration & dosage"
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Item Topical Estrogen Therapy for Hyperopia Correction in Vivo(ARVO Journals, 2020-06-03) Leshno, Ari; Prokai-Tatrai, Katalin; Rotenstreich, Ygal; Magid, Asaf; Bubis, Ettel; Schwartz, Shulamit; Skaat, Alon; Zloto, Ofira; Avni-Zauberman, Noa; Barak, AdielPurpose: In vitro studies found that 17beta-estradiol (estrogen) modulates corneal biomechanical properties and reduces tissue stiffness. Therefore we hypothesized that topical estrogen might affect the refractive properties of the cornea, inducing a myopic shift. Methods: Twelve female New Zealand white rabbits 16 weeks old were used. The rabbits were randomly divided to either the treatment group receiving 1.5% (w/v) estrogen eye drops or a control group receiving vehicle only (n = 6 each group). Both groups were given drops (50 microL) to the right eye every 12 hours for 35 days. Ocular examination, pachymetry, intraocular pressure (IOP), keratometry ,and refraction were evaluated at baseline and on a weekly basis. Results: No significant differences were observed between the two groups at baseline in all outcome measures. Both groups displayed corneal flattening and a hyperopic shift. However, the change rate was slower in the treatment group. Repeated measurements analysis revealed a statistically significant difference in keratometry readings between groups (P = 0.034) with steeper keratometry by up to 0.6 diopters in the treatment group. The difference between the two groups diminished and became statistically insignificant after treatment cessation. No significant changes were observed in IOP and pachymetry throughout the study period. No side effects were observed in either group. Conclusions: Estrogen eye drops induced a myopic shift in keratometry readings. These results suggest that corneal refractive power might be manipulated pharmacologically. Further studies on the physiology behind this change are warranted to facilitate a pathway for development of novel pharmacologic treatments to correct refractive errors.Item Treatment with an orally bioavailable prodrug of 17beta-estradiol alleviates hot flushes without hormonal effects in the periphery(Springer Nature, 2016-08-01) Merchenthaler, Istvan; Lane, Malcolm; Sabnis, Gauri; Brodie, Angela; Nguyen, Vien; Prokai, Laszlo; Prokai-Tatrai, KatalinEstrogen deprivation has a profound effect on the female brain. One of the most obvious examples of this condition is hot flushes. Although estrogens relieve these typical climacteric symptoms, many women do not want to take them owing to unwanted side-effects impacting, for example, the uterus, breast and blood. Therefore, there is a need for developing safer estrogen therapies. We show here that treatment with 10beta,17beta-dihydroxyestra-1,4-dien-3-one (DHED), a novel brain-targeting bioprecursor prodrug of the main human estrogen, 17beta-estradiol, alleviates hot flushes in rat models of thermoregulatory dysfunction of the brain. Oral administration of DHED elicits a significant reduction of tail skin temperature (TST) rise representing hot flushes in the morphine-dependent ovariectomized rat model and results in the restoration of estrogen deprivation-induced loss of diurnal rhythm in TST. These beneficial effects occur without detrimental peripheral hormonal exposure; thus, the treatment avoids potentially harmful stimulation of estrogen-sensitive peripheral organs, including the uterus and the anterior pituitary, or the proliferation of MCF-7a breast cancer cell xenografts. Our promising preclinical assessments warrant further considerations of DHED for the development of a brain-selective 17beta-estradiol therapy to relieve hot flushes without undesirable peripheral side-effects.