Abstract
The beneficial effects of bioidentical ovarian steroid hormone therapy (HT) during the perimenopause are gaining recognition. However, the positive effects of estrogen (E) plus or minus progesterone (P) administration to ovariectomized (Ovx) lab animals were recognized in multiple systems for years before clinical trials could adequately duplicate the results. Moreover, very large numbers of women are often needed to find statistically significant results in clinical trials of HT; and there are still opposing results being published, especially in neural and cardiovascular systems. One of the obvious differences between human and animal studies is diet. Laboratory animals are fed a diet that is low in fat and refined sugar, but high in micronutrients. In the US, a large portion of the population eats what is known as a “western style diet” or WSD that provides calories from 36% fat, 44% carbohydrates (includes 18.5% sugars) and 18% protein. Unfortunately, obesity and diabetes have reached epidemic proportions and the percentage of obese women in clinical trials may be overlooked. We questioned whether WSD and obesity could decrease the positive neural effects of estradiol (E) in the serotonin system of old macaques that were surgically menopausal. Old ovo-hysterectomized female monkeys were fed WSD for 2.5 years, and treated with placebo, Immediate E (ImE) or Delayed E (DE). Compared to old Ovx macaques on primate chow and treated with placebo or E, the WSD-fed monkeys exhibited greater individual variance and blunted responses to E-treatment in the expression of genes related to serotonin neurotransmission, CRH components in the midbrain, synapse assembly, DNA repair, protein folding, ubiquitylation, transport and neurodegeneration. For many of the genes examined, transcript abundance was lower in WSD-fed than chow-fed monkeys. In summary, an obesogenic diet for 2.5 years in old surgically menopausal macaques blunted or increased variability in E-induced gene expression in the dorsal raphe. These results suggest that with regard to function and viability in the dorsal raphe, HT may not be as beneficial for obese women as normal weight women.
Highlights
Today women face two major health issues, menopause and obesity, both of which seriously impact age-related diseases and quality of life
They were old rhesus females provided with biscuits from Lab Diet, Inc. to maintain a healthy body weight plus fresh fruit and vegetables
Raphe gene expression in old obese monkeys inflammation can impact the functions of many physiological systems cumulating in the multiple symptoms of metabolic disease, which often includes depression [25,42]
Summary
Today women face two major health issues, menopause and obesity, both of which seriously impact age-related diseases and quality of life. Bio-identical HT administered during a ‘window of opportunity’ shows promise in some systems for subgroups of women who are not at risk for hormone-sensitive malignant conditions, counter-indications (American Association of Clinical Endocrinologists) or other adverse life events [2]. As obese women enter menopause, an obvious speculation is that their risk for disease could increase over the presence of either risk factor alone [11]. Obesity and WSD cause an increase in systemic cytokine production that in turn, negatively impacts many functions [12,13,14,15,16,17,18]. Obesity and its adjunct cytokines have been linked to depression and neurodegeneration [19,20,21,22,23,24,25,26,27,28]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
