**Acknowledgements**

*Hormone Therapy and Replacement in Cancer and Aging-Related Diseases*

and augment food intake [83].

receptor activity by estrogen [85].

the MCH receptor [89].

*2.5.2 Stress and feeding behavior*

Stress arises, which may increase their eating behavior.

such as the aforementioned arcuate and paraventricular nuclei [81, 82]. Ghrelin regulates food intake by activating the growth hormone receptor according to the fluctuation in carbohydrate and lipid levels. Ghrelin also antagonizes the function of leptin, which promotes a sense of fullness. The antagonizing effect acts through the neuropeptide Y/Y1 receptor pathway, which increases gene expression of NPY

NPY increases food intake potently through the function of the arcuate and paraventricular area in hypothalamus [84]. Estrogen inhibits the orexigenic activity of NPY. This inhibitory action stems from the reduced NPY mRNA expression and

Melanin-concentrating hormone (MCH) promotes feeding behavior by direct action on the lateral nucleus in hypothalamus [86]. The arcuate and POMC neurons can stimulate the MCH activity [87]. Ovariectomized rats treated with estradiol demonstrated reduced orexigenic effect of MCH [88], which is hypothesized to be a direct effect of the reduced expression of MCH mRNA or the decreased affinity of

Stress has been tied to a tendency to overeat and a preference for high-fat and high-sugar foods. Animal studies showed that chronic stress stimulates food intake and inhibits hypothalamic-pituitary-adrenal axis activity induced by acute stress [90]. In humans, food craving after stress can be predicted by high cortisol reactivity in response to stress. Epel et al. found that premenopausal women exposed to a stressful situation had higher cortisol levels and experienced higher calorie consumption, and they also tend to prefer sweets. Negative mood induced by stress also leads to greater food consumption [91]. As women experiencing menopausal transition, they are exposed to a lot of distressing symptoms, such as hot flashes, negative mood, poor sleep, recurring infections of the urogenital tract, and so on.

Further, stress situations can decrease gastric motility. Estrogen has synergistic actions with stress mediators and interacts with neuromodulators [92]. Estrogen also influences gut function by inhibiting smooth muscle contraction. Premenopausal and postmenopausal women demonstrated a decrease in gastric motility under stress, which was similar to the general population. However, the perimenopausal women exhibited lower basal gastric motility but did not reveal a decreased gastric motility in response to stress. This indicated that many gastric changes during menopause are a rapid response to decreased estrogen levels, which happens quickly and can recover with time even without estrogen replacement [93]. Gaining better understanding of the mechanisms of increased appetite during menopausal transition promises to open novel therapeutic solutions for this population. Since the lack of estrogen plays a key role in the disturbances of food intake, MHT is one of the solutions to prevent unfavorable overeating, metabolic distur-

With the aging of world population, the health issue of postmenopausal women has been unprecedented concerned. Obesity is associated with a decline of lifespan. Especially, the increased risk of weight gain, centrally accumulation of body fat, and energy metabolism disorders during the menopausal transition lead to further CVD and rise overall mortality in women. An early intervention of

**106**

bances, and obesity.

**3. Conclusions**

This work was supported by grants from the National Natural Science Foundation of China [81701460 (X. C.)]; the Natural Science Foundation of Zhejiang Province [Y17H040052 (J. S)] and [LQ18H040004 (J. Z.)]; the General Research Program for Medicine and Health of Zhejiang Province [2019KY033 (J.S.)] and [2016KYA029 (J. Z.)]; and the Excellent Young Scientist Foundation of Zhejiang Provincial People's Hospital [ZRY2016A002 (X. C.)].
