Nina Stachenfeld, PhD

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 endometriosis on cardiovascular risk in women with endometriosis, and what we might do to mitigate this risk. We have just completed studies to examine the role of testosterone on blood pressure regulation in women PCOS, who present with mild hypertension. Our studies demonstrated an important role for testosterone both through the nervous and the renal systems in the regulation of blood pressure in women with PCOS.

We have just begun a study to examine cardiometabolic changes in transgender youth in collaboration with Stuart Weinzimer.

R01 HL71159 Title: Estrogen and progesterone effects on orthostatic intolerance P.I. Nina StachenfeldR01 HL135089 Mechanisms of hypertension in women with polycystic ovary syndrome Co-P.I. Nina Stachenfeld; Co- P.i. Jane Reckelhoff (U. of Mississippi)

R01 HL161000 Mechanisms and interventions addressing accelerated cardiovascular disease risk in women with endometriosis Co-P.I. Nina Stachenfeld; Co- P.i. Lacy Alexander (Penn State)

1R21HD107609 Cardiometabolic effects of gender-affirming hormone therapy in transgender adolescents Co-P.I. Co- P.i. Stuart Weinzimer; Co-PI Nina Stachenfeld