Preventive effects of estrogen and progesterone against adiposity are promoted by testosterone in ovariectomized female rats

Some synthetic progestins contained in hormonal drugs (e.g., oral contraceptives) are known to have androgenic activity; however, the roles of such androgenic activity in the regulation of nutrition and metabolism remain unclear. Here, we examined the effects of testosterone on nutrition- and metabolism-related parameters in the presence of both estrogen and progesterone. Female rats were ovariectomized and randomly assigned to a no-treated group (OVX), an estrogen and progesterone-treated group (OVX+EP), or an estrogen, progesterone, and testosterone-treated group (OVX+EPT). Subsequently, change in body weight, food intake, fat weight, adipocyte size, and peripheral and central levels of feeding-related factors were evaluated. The results indicated that body weight and food intake were lower in OVX+EP and OVX+EPT than in OVX, whereas these parameters did not differ between OVX+EP and OVX+EPT. Although fat weight and/or adipocyte size did not differ between OVX+EP and OVX, these parameters were lower in OVX+EPT than in OVX and OVX+EP. Conversely, serum leptin and hypothalamic proopiomelanocortin mRNA levels, which are anorectic factors, were lower in OVX+EPT than in OVX+EP and OVX, suggesting that these are preventive reactions. These findings indicate that estrogen and progesterone supplementation in OVX rats exert some favorable effects on metabolic and nutritional conditions, and that the additional administration of testosterone may promote these actions. Thus, although the androgenic activity of progestin used in some hormonal drugs may not fully correspond to the effects of testosterone in the presence of estrogen and progesterone, testosterone does not necessarily exert adverse metabolic effects and may offer preventive effects against obesity and metabolic disordersunder these conditions.