Integrative Environmental Physiology

Principal Investigator:

Director of the Laboratory for Metabolic Testing and Performance, and Fellow
The John B. Pierce Laboratory

Senior Research Scientist
Obstetrics, Gynecology & Reproductive Sciences & Yale School of Public Health
Yale School of Medicine
Committee on the Status of Women in Medicine (SWIM), Co-Chair
WHRY Pilot Project Program Investigators
Discovery to Cure Internship, Mentor

Research Interests

My laboratory addresses the interaction between reproductive hormones and cardiovascular function in humans.

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrinopathy affecting ~1 in 10 women of reproductive age and is the most common cause of infertility in young women. We study the more severe reproductive and metabolic PCOS phenotype, which is dominated by features of hyperandrogenism and associated with insulin resistance, android type obesity, mild hypertension, early endothelial dysfunction, metabolic syndrome, and atherosclerosis. We study a variety of interventions with this clinical population, including exercise and hormonal interventions to determine the causes of their cardiovascular disease. Our latest project addressed the impact of testosterone on blood pressure dysregulation in women with PCOS.

Endometriosis is an estrogen dependent gynecological disorder associated with considerable chronic pelvic pain and pain during intercourse, which affects 6% – 10% of reproductive age women and is a major cause of infertility. Epidemiologic data demonstrate a clear association between endometriosis, reproductive risk factors, inflammation and cardiovascular disease risk, the leading cause of death in women worldwide. Estrogen exposure is beneficial for women from a cardiovascular standpoint, but the standard of treatment for endometriosis includes estrogen suppression, creating a conundrum for the long-term management of cardiovascular risk in women with endometriosis. We are exploring the impact of losing estrogen protection on the vascular system in women with endometriosis.

In the US approximately 0.7-1.8% or ~ 275,000 youth identify as transgender or having a gender identity that differs from the sex assigned at birth. In transgender men, testosterone treatment with gender affirming hormone therapy (GAHT) is associated with dyslipidemia, thrombosis, increased blood pressure and compromised vascular function. In transgender women, estrogen treatment with androgen suppression results in similar cardiometabolic changes, in addition to changes in insulin resistance and risk of thrombosis. It is likely these large changes in hormonal milieu are central to the link between GAHT and cardiometabolic risk in transgender individuals. This relationship has not been well studied in transgender youth, so our laboratory is currently addressing cardiometabolic changes in transgender adolescents.

Our laboratory has also assisted Yale University Athletics with performance testing on the Men’s and Women’s Hockey, Men’s Football, and Lacrosse teams.

Current Projects

With our colleagues at Penn State (Noll Laboratory) we are studying the effects of estrogen suppression on inflammation and vascular dysfunction in women with endometriosis and the potential use of Selective Estrogen Receptor Modulators (SERMs) and anti-inflammatory interventions to improve vascular function in endometriosis.

To participate in our research studies click here.

In collaboration with our colleagues in the Yale Gender Program we are studying the effects of gender affirming hormone therapy (GAHT) on changes in the vascular system and insulin/glucose regulation in male and female adolescents.

Recent Publications

Dillon GA, Stanhewicz AE, Serviente C, Flores VA, Stachenfeld N and Alexander LM. Seven days of statin treatment improves nitric-oxide mediated endothelial-dependent cutaneous microvascular function in women with endometriosis. (2022) Microvasc Res. 144, 104421 Pubmed Microvasc Res

Mamillapalli R, Toffoloni N, Habata S, Qunhua H, Atwani R, Stachenfeld N and Taylor HS. Endometriosis promotes atherosclerosis in a murine model. (2022) Am J Obstet Gynecol. 227, 248.e1-248.e8 Pubmed Am J Obstet Gynecol PMC Article

Gomez JMD, VanHise K, Stachenfeld N, Chan JL, Merz NB and Shufelt C. Subclinical cardiovascular disease and polycystic ovary syndrome. (2022) Fertil Steril. 117, 912-923 Pubmed Fertil Steril

Stachenfeld NS and Mazure CM. Precision medicine requires understanding how both sex and gender influence health. (2022) Cell. 185, 1619-1622 Pubmed Cell

Giersch GEW, Garcia CK, Stachenfeld NS and Charkoudian N. Are there sex differences in risk for exertional heat stroke? A translational approach. (2022) Exp Physiol. Pubmed Exp Physiol

Shawky NM, Dalmasso C, Ojeda NB, Zuchowski Y, Stachenfeld N, Alexander BT and Reckelhoff JF. Consequences of hyperandrogenemia during pregnancy in female offspring: attenuated response to angiotensin II. (2022) J Hypertens. 40, 712-722 Pubmed J Hypertens PMC Article

Stachenfeld NS and Alexander LM. Why gender equity should remain a focus for the American Physiological Society. (2022) Am J Physiol Heart Circ Physiol. 322, H575-H578 Pubmed Am J Physiol Heart Circ Physiol

Wenner MM and Stachenfeld NS. Point: Investigators should control for menstrual cycle phase when performing studies of vascular control that include women. (2020) J Appl Physiol (1985). 129, 1114-1116 Pubmed J Appl Physiol (1985)

Wenner MM and Stachenfeld NS. Rebuttal to Drs. Stanhewicz and Wong. (2020) J Appl Physiol (1985). 129, 1120 Pubmed J Appl Physiol (1985)

Wenner MM and Stachenfeld NS. Last Word on Point:Counterpoint: Investigators should/should not control for menstrual cycle phase when performing studies of vascular control that include women. (2020) J Appl Physiol (1985). 129, 1136-1137 Pubmed J Appl Physiol (1985)

Stone T and Stachenfeld NS. Pathophysiological effects of androgens on the female vascular system. (2020) Biol Sex Differ. 11, 45 Pubmed Biol Sex Differ PMC Article

Stachenfeld N. Introducing a special series, sex as a variable in human research: A systems approach. (2020) FASEB J. 34, 8776-8777 Pubmed FASEB J