Ovarian Dysfunction, Stress, and Disease: A Primate Continuum

Abstract

Menopause is recognized as a period of increased risk for coronary heart disease (CHD) and osteoporosis. Vulnerability to these conditions is often attributed to the naturally occurring estrogen deficiency characteristic of this part of the life cycle. Premenopausal reductions in endogenous estrogen occasioned by functional ovarian abnormalities or failure are hypothesized to be similarly pathogenic and to accelerate development of CHD and osteoporosis prematurely, thereby increasing the health burden of older women. These functional abnormalities, which occur along a continuum from mild, luteal phase progesterone deficiency to amenorrhea, are relatively common and are often attributed to psychogenic factors (stress, anxiety, depression, or other emotional disturbance), exercise, or energy imbalance. Although numerous investigators have commented on these functional deficits, the abnormalities can be difficult to diagnose and are generally unappreciated for the contribution they may make to postmenopausal disease. Studies in nonhuman primates confirm that these deficits are easily induced by psychological stress and exercise, and that they accelerate the development of cardiovascular disease and perhaps bone loss in the presence of a typical North American diet. However, functional reproductive deficits are also reversible and are thus potentially amenable to environmental or behavioral intervention. Data from both women and nonhuman primates support the hypothesis that functional reproductive deficits are adaptive when triggered appropriately but are detrimental when activated in an environment (e.g., sedentary lifestyle, high-fat diet) permissive to the development of chronic disease.

Polymorphisms in the serotonin reuptake transporter gene modify the consequences of social status on metabolic health in female rhesus monkeys

“…As new groups formed, females attained specific dominance positions from 1 through 5. For analysis, females ranked 1 and 2 were considered dominant and females ranked 3-5 were considered subordinate [50]. Table 2 Mean±SEM for rates (number per hour) for the initiation of affiliative, aggressive, submissive, or anxiety-like behavior and for the duration of affiliative behavior during each week following the formation of the new groups for dominant l/l; dominant s-variant; subordinate l/l; and subordinate s-variant females Table 3 Metabolic hormone concentrations (mean±sem) obtained at baseline and week 7 after the formation of the new groups …”

“…Dominance status was determined by the outcome of unequivocal dyadic agonistic interactions [27]. Using previously described conventions [50], females were categorized as dominant (ranks 1 and 2) or subordinate (ranks 3, 4, and 5) for analysis. Using this approach, group sizes were: dominant, l/l genotype n=8; dominant, s-variant genotype n=8; subordinate, l/l genotype n=12; and subordinate, s-variant genotype n=12 (see Table 1).…”

“…In addition to stimulating gluconeogenesis, glucocorticoids increase appetite and locomotor activity, responses that would normally constitute adaptive mechanisms for survival [1]. In contrast, chronic activation of stress-response mechanisms can elevate blood pressure, exacerbate the development of atherosclerosis, adversely alter carbohydrate metabolism, reduce immune function, and disrupt the reproductive axis [2][3][4][5][6].…”

Discordant Orthostatic Reflex Renin–Angiotensin and Sympathoneural Responses in Premenopausal Exercising-Hypoestrogenic Women

“…8,9 However, in contrast to postmenopausal women, ExFHA women have lower resting systolic blood pressure (SBP) and heart rate (HR) than age-and fitness-matched estrogen-replete physically active women.…”

“…7 Cardiovascular consequences of premenopausal hypoestrogenemia in ExFHA women are not yet known, but disruption of the menstrual cycle during the reproductive years is also associated with the premature development and progression of coronary artery disease. 8,9 However, in contrast to postmenopausal women, ExFHA women have lower resting systolic blood pressure (SBP) and heart rate (HR) than age-and fitness-matched estrogen-replete physically active women. 10,11 The presence of low arterial BP, despite hypoestrogenemia, suggests that estrogen deficiency may have different consequences for BP regulation in premenopausal and postmenopausal women.…”