Sex, Gender, and Transgender: Metabolic Impact of Cross Hormone Therapy.

Most preclinical and clinical, animal, and human research has been biased with respect to sex and even more so with respect to gender. In fact, little is known about the impact of sex and even less about the influence of gender on overall metabolic processes. The National Institutes of Health has recognized this gap in scientific knowledge and now mandates that studies be conducted in both sexes and to include gender as variables influencing physiological processes such as metabolism. It is therefore critical to understand and appreciate how to incorporate sex and gender in preclinical and clinical research in order to enhance our understanding of the mechanisms by which metabolic processes differ by sex and gender. In this chapter, we define sex and gender and discuss when sex and gender are not aligned, such as that which occurs in transgender individuals, and how this impacts metabolic processes. We discuss the importance of understanding the influence and interactions between sex hormones and sex chromosomes rather than focusing on their relative contributions to metabolism in isolation. This knowledge will optimize therapies specific for individuals which need to encompass sex and gender.

Overweight postmenopausal women with different plasma estradiol concentrations present with a similar pattern of energy expenditure and substrate oxidation rate before and after a fatty meal challenge.

Menopause-related withdrawal of ovarian estrogens is associated with reduced energy metabolism and overall impairment of substrate oxidation. Estradiol's withdrawal after menopause is associated with a reduction in energy metabolism and impaired substrate oxidation, which contributes to weight gain and visceral fat accumulation. Here we aimed to investigate the association between plasma estradiol concentrations and energy expenditure (EE)/substrate oxidation in a group of overweight postmenopausal women before and after a fatty meal challenge. Women were divided into three groups according to their plasma estradiol concentrations (E2): group 1 - E2 ≤ 39, group 2 - 40 ≤ E2 ≤ 59, and group 3 - E2 ≥ 60 pg/mL. VO2 and VCO2 volumes were collected following indirect calorimetry 5 h following a single lipid overload meal (1100 kcal, 72% of fat). For comparisons between groups and within the same group, a linear regression model with mixed effects was applied (P < 0.05). Forty-four women aged 55 ± 0.7 years-old, 8 ± 1.1 years following menopause, with a BMI of 30.5 ± 0.5 kg/m2, and 41.9 ± 0.7% of body fat were enrolled the study. Plasma E2 concentrations were: group 1 - 30.4 ± 1.9, group 2 - 46.9 ± 1.5, and group 3 - 91.3 ± 12.0 pg/mL (P < 0.0001). EE at baseline and in the resting state was 1320 ± 24.3 kcal/d, and increased to 1440 ± 27.0 kcal/d 30 min following ingestion of the fatty meal (P < 0.0001), and rose again to an average of 1475 ± 30.3 kcal/d at the completion of experiment (P < 0.0001). Carbohydrate oxidation (Chox) was 0.155 ± 0.01 g/min at resting, maintained as 0.133 ± 0.00 g/min 30 min after ingestion of the fatty meal, and was 0.123 ± 0.01 g/min at the end of the testing period. Lipid oxidation (Lipox) was 0.041 ± 0.003 g/min at resting, increasing to 0.054 ± 0.003 g/min at 30 min (P = 0.01), and reaching 0.063 ± 0.003 g/min at the end of the experiment (P < 0.0001). There was no difference between groups for EE, Chox or Lipox. Our data suggest that EE and substrate oxidation were modulated following a lipid-meal challenge equally in all groups and this did not differ with plasma E2 concentrations.