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Reproductive Physiology & Pathophysiology Group

Neuroendocrinology of Reproduction and Aging

Janet Hall
Janet E. Hall, M.D., M.S.
NIEHS Clinical Director and Principal Investigator
Tel 919-316-4525
janet.hall@nih.gov
P.O. Box 12233
Mail Drop A2-03
Durham, N.C. 27709

Research Summary

Janet Hall, M.D., M.S., serves as NIEHS Clinical Director, head of the Reproductive Physiology and Pathophysiology Group and holds a secondary appointment in NIEHS Reproductive and Developmental Biology Laboratory.

The Reproductive Physiology and Pathophysiology Group studies the mechanisms involved in the integrated control of the reproductive system in women and its disruption in reproductive disorders. The research focus, within the broad area of women’s health, is on the neuroendocrine interactions that govern normal reproduction and the changes that occur with aging. The group has used this information as a backdrop to provide insights into the pathophysiology of clinical reproductive endocrine disorders, translating this information to provide physiologically-based treatments.   

Investigation of the neuroendocrine control of the reproductive system in women requires the use of a combination of complementary models. To this end, group members have studied pre- and post-menopausal women and women with a congenital deficiency in the secretion or responsiveness to hypothalamic gonadotropin-releasing hormone (GnRH). In these studies, Hall and her group utilized frequent blood sampling for measurement of LH and gonadotropin free alpha subunit as markers of GnRH secretion and developed and utilized physiologic probes including GnRH, GnRH agonists and antagonists and estradiol, estrogen receptor blockers and aromatase inhibitors, as well as neuroimaging modalities.

physiological interactions between hypothalamus gland, pituitary gland and ovaries
The diagram depicts the physiological interactions that form the basis of research for Hall's group. Repeated reproductive cycles in women require the tight integration of signals from the hypothalamus (gonadotropin-releasing hormone [GnRH]) to the pituitary, resulting in secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH). These hormones are responsible for follicle growth within the ovary and secretion of estradiol and progesterone, inhibin A and inhibin B. In addition to its effect on reproduction, estrogen impacts cognition, mood, and vasomotor symptoms, additional areas of interest in the Hall lab.

Major areas of research:

  • Understanding the integration of hypothalamic, pituitary, and ovarian signals responsible for repeated cycles of development and ovulation of a single dominant follicle in women
  • Determining the role of neuroendocrine disruption in menstrual cycle dysfunction including hypothalamic amenorrhea and polycystic ovarian syndrome
  • Understanding the neuroendocrine and ovarian contributions to reproductive aging and determining the effect of aging on neurocognitive responses to estrogen
  • Genotype/phenotype relationships in GnRH deficiency

Current projects:

  • Utilizing physiologic GnRH replacement in women with GnRH deficiency for ovulation induction and to further the understanding of the genetic underpinnings of this disorder
  • Determining the role of genes involved in congenital hypogonadotropic hypogonadism in functional hypothalamic amenorrhea
  • Investigating factors that determine the variable susceptibility to disruption of GnRH secretion in normal women in response to environmental stressors frequently associated with hypothalamic amenorrhea

Hall is an internationally known clinician and clinical investigator. She received her Masters of Medical Sciences in exercise physiology and her M.D. and Internal Medicine training at McMaster University in Ontario, Canada. She completed her training in Endocrinology and Metabolism at Massachusetts General Hospital in Boston and rose to the rank of Professor of Medicine at Harvard Medical School. She had continuous NIH extramural grant funding until moving to the NIEHS intramural program in 2015. Hall was elected to the Association of American Physicians in recognition of her contributions to both the science and academics of medicine and, as a leader in the field, is a former President of the Endocrine Society.