Natural remedies for hot flashes without hormones

#Natural remedies for hot flashes without hormones skin#

This prodrug also possesses favorable physicochemical properties for blood-brain barrier transport compared to those of E 2.

We have recently reported that a small-molecule compound, 10ОІ,17ОІ-dihydroxyestra-1,2-dien-3-one (DHED), is an inactive bioprecursor prodrug of 17ОІ-estradiol (E 2) converting to E 2 only in the brain 15. A prodrug is inert and remains inactive until in vivo bioconversion to the active agent 15. A plausible solution to this challenge is to confine the beneficial effect of estrogens into the brain via a unique prodrug design. Hence, there is an unmet need for developing efficacious estrogen therapies with improved safety profile. The efficacy of these alternate therapies, however, is minimal-usually just above the placebo effect and they can also carry side effects. Therefore, many women turned to non-steroid-based therapies including soy products, serotonin and norepinephrine reuptake inhibitors, clonidine, and gabapentine 11, 12, 13, 14. High levels of circulating estrogens may also have cardiovascular liability causing deep venous thrombosis with subsequent pulmonary embolism 9, 10. These side effects occur in the periphery, including in the uterus and in the breast, where estrogen may stimulate cell proliferation and even malignancy. It has been shown that estrogens prevented the ovariectomy- (OVX-) induced TST changes in two established animal models of hot flushes in the morphine-dependent pharmacological model 7 and in a вЂњphysiologicalвЂќ model involving estrogen-dependent diurnal oscillation of TST 4, 8.ДЄmong current therapies, only estrogen (alone or combined with a progestin) can alleviate hot flushes completely, but many women cannot or do not want to take estrogens because of their potential side effects.

#Natural remedies for hot flashes without hormones skin#

In addition to the predominant hypothalamic mechanisms, tail skin temperature (TST) regulation may also involve local estrogen receptors 6. Although hot flushes are characteristic events of primates, the close association between estrogens and thermoregulation makes rodent models useful to evaluate the utility of novel approaches against hot flushes. Some studies in rats suggest that the sensitivity of these thermoregulatory neurons is affected by estrogens, norepinephrine, serotonin 4 and neurokinin B 5. It has been suggested that a slight elevation in core body temperature is sensed by heat-sensitive neurons in the hypothalamus ( thermostat), which activates the descending sympathetic nervous system to dissipate heat by vasodilation and sweating ( hot flush) 3. The mechanism of hot flushes is not well understood. They represent the most prevalent neurological symptom for which women seek remediation 1, 2. Hot flushes are the most common and characteristic symptoms associated with the female climacterics and they negatively affect the quality of life. One of the best demonstrations of how estrogen deprivation affects brain function is the peri-menopausal hot flushes due to sudden decline in circulating estrogen levels. Our promising preclinical assessments warrant further considerations of DHED for the development of a brain-selective 17ОІ-estradiol therapy to relieve hot flushes without undesirable peripheral side-effects. 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. 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. We show here that treatment with 10ОІ,17ОІ-dihydroxyestra-1,4-dien-3-one (DHED), a novel brain-targeting bioprecursor prodrug of the main human estrogen, 17ОІ-estradiol, alleviates hot flushes in rat models of thermoregulatory dysfunction of the brain. Therefore, there is a need for developing safer estrogen therapies. 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. One of the most obvious examples of this condition is hot flushes. Estrogen deprivation has a profound effect on the female brain.