Sex Differences in Biological Systems and the Conundrum of Menopause: Potential Commonalities in Post-Menopausal Disease Mechanisms

Sex-specific differences in biology and physiology likely start at the time of conception and progress and mature during the pre-puberty time frame and then during the transitions accompanying puberty. These sex differences are impacted by both genetics and epigenetic alterations during the maturation process, likely for the purpose of preparing for successful reproduction. For females, later in life (~45–50) they undergo another transition leading to a loss of ovarian hormone production at menopause. The reasons for menopause are not clear, but for a subset of females, menopause is accompanied by an increased risk of a number of diseases or conditions that impact a variety of tissues. Most research has mainly focused on the target cells in each of the affected tissues rather than pursue the alternative option that there may be commonalities in the development of these post-menopausal conditions in addition to influences on specific target cells. This review will address some of the potential commonalities presented by an integration of the literature regarding tissue-specific aspects of these post-menopausal conditions and data presented by space flight/microgravity (a condition not anticipated by evolution) that could implicate a loss of a regulatory function of the microvasculature in the risk attached to the affected tissues. Thus, the loss of the integration of the paracrine relationships between endothelial cells of the microvasculature of the tissues affected in the post-menopausal environment could contribute to the risk for post-menopausal diseases/conditions. The validation of this concept could lead to new approaches for interventions to treat post-menopausal conditions, as well as provide new understanding regarding sex-specific biological regulation.