A novel animal model to study hot flashes

Albertson, Asher J.; Skinner, Donal C.

doi:10.1097/gme.0b013e3181a9f60b

Cited by 7 publications

(2 citation statements)

References 52 publications

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“…We herein induced menopause at the age of seven (natural life expectancy: 10-12 y) by castration. Ovariectomy in sheep unequivocally induces menopause with all systemic consequences observed in women (ie, cardiovascular disorders, 13 hot flushes, 43 or osteoporosis 12 ), as this does also in women undergoing bilateral ovariectomy. 44 Another measure we could have taken in this respect is estrogen levels.…”

Section: Discussionmentioning

confidence: 84%

The ewe as an animal model of vaginal atrophy and vaginal Er:YAG laser application

et al. 2020

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Objective: In sheep of reproductive age, we aimed to document decrease in epithelial thickness, glycogen amount, and other vaginal changes after castration and the effect of Er:YAG laser as used clinically.Methods: On day 0, 16 sheep underwent ovariectomy. They were randomized to sham or three vaginal Er:YAG laser applications at monthly intervals. Primary outcome was vaginal epithelial thickness (d60, d71, d73, d77, and d160). Secondary outcomes included indicators of atrophy (vaginal health index ¼ VHI), pH, cytology, morphology at the above time points, microcirculation focal depth (FD; d70 and d160), and at sacrifice (d160) vaginal dimensions and active and passive biomechanical testing.Results: Menopausal changes between 60 and 160 days after ovariectomy included a progressive decrease in epithelial thickness, in VHI, FD, glycogen, elastin content and vasculature, and an increase in pH and collagen content. In lasered animals, the first day few white macroscopic foci were visible and an increased pH measured. Both disappeared within 3 days. Seven days after laser the epithelial thickness increased. At sacrifice (d160), there were no differences between sham and laser group in vaginal dimensions, morphometry, mitotic and apoptotic activity, active contractility, vaginal compliance, except for a lower blood vessel density in the lamina propria of the midvagina in laser group.Conclusions: In reproductive sheep, ovariectomy induces vaginal atrophy evidenced in different outcome measurements. Vaginal Er:YAG laser induced visual impact, a short-term increase in epithelial thickness yet no long-term changes compared to sham therapy in menopausal controls.

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Section: Discussionmentioning

confidence: 84%

The ewe as an animal model of vaginal atrophy and vaginal Er:YAG laser application

et al. 2020

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“…To provide evidence for the DHED-derived E2 formation in the ORDX rat brain (Figure 1), we conducted an in vivo experiment relying on the determination of E2 content in the hypothalamus through a quantitative assay based on liquid chromatography coupled with tandem mass Although hot flushes are characteristic events of primates, only a limited number of studies have been published using a handful of non-human primates actually [21][22][23]. Recently, an ewe model was also proposed to study peripheral skin temperature changes associated with menopause [24]. On the other hand, owing to the close association between estrogens and thermoregulation in several species, the use of convenient rodent models has been suitable to evaluate the effects of novel preclinical therapies focused on hot flushes [17,[25][26][27].…”

Section: E2 Concentration Increased In the Hypothalamus Without Incrementioning

confidence: 99%

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

et al. 2020

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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 receptor gene expression in the hypothalamus without stimulating galanin expression in the anterior pituitary, further indicating the lack of systemic estrogen exposure upon oral treatment with DHED.

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Factors That May Influence the Experience of Hot Flushes by Healthy Middle-Aged Women

Ziv‐Gal¹,

Flaws

2010

Journal of Women's Health

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Background: Interest in menopausal symptoms in general and hot flushes (HFs) in particular has grown in recent years. This is mostly due to increased awareness and the vast impact these symptoms have on women's lives. Despite the high prevalence of women who experience HFs, a definitive etiology for HFs is yet to be found. Our objective was to review the current literature dealing with associated factors for experiencing HFs and to provide a synthesized overview on this common and often debilitating condition. Methods: We systematically searched the English-language literature in the PubMed database using relevant key words and included only those articles that contained information on associated factors for HFs in generally healthy midlife women. Results: Both conflicting scientific results between studies documenting factors that influence HFs and the lack of validated measuring tools make it difficult to truly pinpoint associated factors for HFs. Nonetheless, we identified the following clusters of associated factors: the menopausal stages, sex steroid hormones, other endocrine agents, genetic polymorphisms, race=ethnicity, body mass index (BMI) and obesity, mood disorders, smoking, soy isoflavones and phytoestrogens, alcohol consumption, and physical activity. Conclusions: No single associated factor was consistently identified as having a major role in experiencing HFs. More resources should be directed to develop a unified study system along with multivariable analyses to get a better understanding of this condition, which often imposes a tremendous social and personal toll on the women who experience it.

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A novel animal model to study hot flashes

Cited by 7 publications

References 52 publications

The ewe as an animal model of vaginal atrophy and vaginal Er:YAG laser application

The ewe as an animal model of vaginal atrophy and vaginal Er:YAG laser application

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

Factors That May Influence the Experience of Hot Flushes by Healthy Middle-Aged Women

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