FIGURE 4.

Conceptual model of the possible relationship between bilateral oophorectomy, premature loss of estrogen, and accelerated aging

The central part of the figure was derived from figures in Refs. 10 and 33. Although in our model we postulate that estrogen plays a major role, the link between bilateral oophorectomy and accelerated aging may be mediated completely or in part by the loss of other ovarian hormones (e.g., premature loss of progesterone, testosterone, or inhibin, or disruption of the hypothalamus-pituitary-ovarian axis). Hormone therapy, primarily estrogen therapy, can attenuate the harmful effects of the premature loss of ovarian hormones caused by the oophorectomy. The minus sign indicates an antagonistic effect against accelerated aging (protective effect against aging). The genetic variants in the estrogen synthesis or responsiveness pathway may increase or decrease the effects of the hormonal loss (plus and minus sign). Similarly, behavioral or environmental risk factors may increase or decrease the effects of the hormonal loss (plus and minus sign). In this scenario, hormonal therapy, genetic factors, and non-genetic factors play a role as effect modifiers (interaction variables). COPD, chronic obstructive pulmonary disease.