Neuroendocrinology of Menopausal Flushes: An Hypothesis of Flush Mechanism

Casper, Robert F.; Yen, S. S. C.

doi:10.1111/j.1365-2265.1985.tb03243.x

Cited by 204 publications

(98 citation statements)

References 117 publications

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confidence: 99%

Effects of Progesterone on the Elevation of Tail Skin Temperature in Ovariectomized Rats.

Kobayashi

Tamura²,

Hayashi³

et al. 2000

JJP

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Menopausal hot flushes (HFs) are the major climacteric symptoms and occur in most climacteric women [1,2]. This symptom manifests as a transient increase in skin temperature in the face and peripheral parts of the extremities. The cause of the occurrence of HFs is the cessation of the ovarian production of sex hormones (i.e., estrogens and progestins) after menopause; and estrogens, especially estradiol (E 2 ), are considered to be the main factors responsible for generating HFs [3,4]. Thus estrogens are the primary agent for hormone replacement therapy for climacteric women, whereas progestins are commonly used with estrogens for inhibiting the side effects of estrogens on the uterus. However, only a single administration of progesterone (P) or its analogue has been reported to be effective for the treatment of HFs with almost the same efficacy as those of estrogens [5][6][7][8][9]. This clinical evidence suggests that progesterone as well as estrogens may be important for controlling the generation of HFs.By using rat tail, which is useful for studying skin temperature regulation [10], we previously demonstrated that the tail skin temperature (TST) in female rats was elevated after ovariectomy and suggested that this thermoregulatory change, which indicated the augmentation of vasodilatory heat dissipation, was relevant to human symptoms of menopausal HFs [11,12]. In this experimental system, we also demonstrated the inhibitory effect of E 2 posttreatment on the elevation of the TST and indicated the decrease in the E 2 level to be involved in the TST elevation induced by ovariectomy [11,12]. However, because we haven't evaluated the effects of P in this model, we examined the effects of P on the elevation of the TST, starting the treatment just after the ovariectomy. Furthermore, we also examined the effects of E 2 by the same protocol as that used for P and compared the results to evaluate the degree of involvement of both ovarian hormones in the development of the TST elevation induced by ovariectomy. Materials and MethodsAnimals. Specific pathogen-free (SPF) female Sprague-Dawley rats purchased from Charles River Japan (Yokohama, Japan) were used in these experiments. The rats were housed under a 12 : 12-h light/dark cycle with lights on at 0600 h in a thermoregulated room maintained at 24.0Ϯ2.0°C. Humidity was maintained in the range of 55Ϯ10%, and food (CE-2, Clea, Tokyo, Japan) and water were provided ad libitum. A bilateral ovariectomy or sham operation was performed on the rats at the age of 11 to 12 weeks. The experimental protocols were in accordance with the regulation of the Animal Care and Use Committee of our Institute.Temperature recording. Temperature record- Key words: progesterone, tail skin temperature, ovariectomy. Abstract:We examined the effects of progesterone on the elevation of tail skin temperature (TST) in ovariectomized rats and compared them with those of estradiol. Progesterone showed only insignificant effects on the TST elevation, whereas estradiol showed complete inhibition. T...

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Effects of Progesterone on the Elevation of Tail Skin Temperature in Ovariectomized Rats.

Kobayashi

Tamura²,

Hayashi³

et al. 2000

JJP

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“…This process allows inappropriate heat-loss mechanisms to be triggered by subtle changes in core body temperature. [3][4][5][6][7][8] Treatment with oestrogen and progestagen can ameliorate these symptoms, but there is controversy about their use in women with breast cancer. 9-12 A trial of hormone replacement therapy in women with breast cancer was terminated early because of the finding that the treatment increased the risk of recurrence.…”

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Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial

Pandya¹,

Morrow²,

Roscoe³

et al. 2005

The Lancet

299

160

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“…Downregulation of the pituitary-ovarian axis by exogenous LHRH has been used to treat reproductive disorders including endometriosis and premenstrual syndrome [20,22]. The major limitations of this treatment are mental de pression and altered thermoregulation due to E2 deprivation in the brain [8] as well as accelerated bone loss due to peripheral E2 deficiency [22].…”

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Chronic Inhibition of Hypothalamic-Pituitary-Ovarian Axis and Body Weight Gain by Brain-Directed Delivery of Estradiol-17β in Female Rats

et al. 1989

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The effect of preferential delivery of estradiol (E2) into the brain on both the hypothalamic-pituitary-ovarian axis and weight gain was studied in female rats. When E₂ was coupled to a lipoidal dihydropyridine-pyridinium carrier, the resulting carrier E₂ complex (CE), upon a single intravenous administration to cycling female rats, caused a dose-dependent inhibition of ovulation which lasted 3 times longer than with uncoupled E₂. The dose of CE that delayed ovulation for 4 days was one twentieth the amount of E₂ needed to produce the same effect. Studies in ovariectomized (OVEX) rats indicated that the prolonged ovulation-blocking action of CE appeared to be related to a sustained storage and release of E₂ in the brain, which in turn suppressed the release of hypothalamic luteinizing hormone-releasing hormone (LHRH) and pituitary luteinizing hormone (LH). Upon single intravenous administration in pubertal female rats, CE caused a dose-dependent reduction of body weight gain for a minimum period of 28 days. The inhibitory action of CE on body weight gain was more potent and longer lasting than that of E₂ in pubertal rats. When administered in OVEX rats, CE produced a loss of body weight that lasted significantly longer than that produced by uncoupled E₂ in these rats. These results suggest that the biological action of E₂ can be potentiated by this novel chemical delivery system.

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Neuroendocrinology of Menopausal Flushes: An Hypothesis of Flush Mechanism

Cited by 204 publications

References 117 publications

Effects of Progesterone on the Elevation of Tail Skin Temperature in Ovariectomized Rats.

Effects of Progesterone on the Elevation of Tail Skin Temperature in Ovariectomized Rats.

Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial

Chronic Inhibition of Hypothalamic-Pituitary-Ovarian Axis and Body Weight Gain by Brain-Directed Delivery of Estradiol-17β in Female Rats

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