Research & Publications
Cardiovascular disease is the biggest killer of women. It is clear that hormones involved primarily in reproductive function, including estrogens, progesterone and androgens have important effects on the cardiovascular function and health in women.
We have examined these systems in older post-menopausal, women before and during treatment with estrogen. We have also used the birth control pill to control the levels of estrogen and progesterone in young women. We have used medications to temporarily suppress the menstrual cycle in young women while adding back estrogen, progesterone or testosterone to study the effects of these hormones on body fluid regulation under more controlled conditions. We also examine the impact of these hormones on cardiovascular health and function in women with Polycystic Ovary Syndrome, endometriosis and in transgender people.
Specialized Environmental physiology; Reproductive hormone effects on temperature and body fluid regulation; Polycystic Ovary Syndrome; Orthostatic tolerance; Blood pressure regulation
Extensive Research Description
Adequate body fluid and cardiovascular regulation are essential to respond to environmental challenges. Over my first years at Yale we demonstrated that estradiol, with and without progesterone, alters the osmotic regulation of arginine vasopressnin (AVP). Moreover, my laboratory has shown under a variety conditions and within both aging and younger populations that this is a change in osmotic set point for the control of AVP. We came to this conclusion because there is little change in renal free water clearance, the primary fluid regulation variable controlled by AVP. In addition we demonstrated that estradiol and progesterone not only affect osmotic regulation of AVP, but also affect body fluid distribution across the compartments (interstitial, intra- and extra-cellular, plasma) and may have important implications for the development of edema in women.
More importantly, in order to deal with challenges associated with studying reproductive hormone effects on physiological systems, we developed a model to study effects of reproductive hormones on physiological systems in young women. In this model we “medically oophorectomize” young women by transiently suppressing gonadotropin releasing hormone (GnRH) with an agonist (leuprolide acetate) or antagonist (ganirelix acetate). Both of these drugs suppress GnRH and therefore suppress both estrogens and progesterone. Recently, a new drug, elagolix has become available that accomplishes the same goal.
While the women are suppressed, we add-back controlled levels of estradiol and progesterone to test the hypothesis of interest. This protocol is particularly useful because it isolates estradiol, progesterone or testosterone effects in young women. Other methods of studying estradiol effects in young women (such as pregnancy, oral contraceptives, menstrual cycle phase) can only indirectly infer estradiol-related effects because other physiological changes are taking place simultaneously. This model provides a unique opportunity to examine the effect of the chosen sex hormone on a variety of system.
Our studies now address more directly hormonal effects on cardiovascular function in women, including those of estrogens, progesterone and androgens on endothelial function in women with PCOS, endometriosis and in transgender men.
Our research continues to examine the effects of reproductive hormones (now including testosterone) on cardiovascular regulation, thermoregulation and fluid regulation in young, healthy women and in women with Polycystic Ovary Syndrome (PCOS), endometriosis and transgender people.
My current grant addresses the impact of testosterone on blood pressure regulation in women PCOS, who present with mild hypertension. Our studies will determine the roles of both the autonomic and renal systems in the regulation of blood pressure in women with PCOS in this syndrome, and will also explore the peripheral mechanisms involved. We will also determine the extent to which testosterone contributes to their mild hypertension. To study mechanisms related to blood pressure regulation in PCOS we use drug infusions, lower body negative pressure and microneurography to examine the extent to which sympathetic nervous system activity mediates sex hormone effects on blood pressure regulation.
R01 HL71159 Title: Estrogen and progesterone effects on orthostatic intolerance P.I. Nina Stachenfeld
R21 HL093450 Title: Compromised microcirculation in women with Polycystic Ovary Syndrome P.I. Nina Stachenfeld
R01 HL135089 Mechanisms of hypertension in women with polycystic ovary syndrome Co-P.I. Nina Stachenfeld; Co- P.i. Jane Reckelhoff (U. of Mississippi)
Blood Pressure; Environment and Public Health; Gynecology; Physiology; Polycystic Ovary Syndrome; Reproductive Medicine; Orthostatic Intolerance