David Ehrmann, M.D.

APPOINTMENTS

  • Professor, Department of Medicine - Section of Endocrinology, Committee on Molecular Metabolism and Nutrition, Committee of Clinical & Translational Science 

EDUCATION

M.D., University of Michigan, 1982

CONTACT INFORMATION

The University of Chicago
AMB M270, (MC 1027)
5841 South Maryland Avenue
Chicago, Illinois 60637

dehrmann@medicine.bsd.uchicago.edu

Phone: (773) 702-9653

Website (Medical Center)
Website (Department of Medicine)

RESEARCH SUMMARY

Pathogenesis and Therapy of Hyperandrogenic States and Genetics of Insulin Secretion and Action in Polycystic Ovary Syndrome (PCOS)

Pathogenesis and Therapy of Hyperandrogenic States

Our clinical research studies have been designed to define the mechanisms of ovarian and/or adrenal androgen excess in women presenting with menstrual disturbances, hirsutism, acne and obesity. We have found that women with well-defined PCOS have a characteristic pattern of ovarian steroid secretion in response to the endogenous gonadotropin secretion induced by administration of a gonadotropin releasing hormone agonist. This response, a supranormal elevation of 17-hydroxyprogesterone, suggests abnormal regulation of androgen formation by ovarian 17-hydroxylase and 17, 20-lyase activities and appears to be a unique means for the detection of the functional ovarian hyperandrogenism of polycystic ovary syndrome. In addition, a similar abnormality of ovarian and adrenal steroidogenesis has been elucidated. This abnormality appears to be due to abnormal regulation of the androgen-forming enzyme, cytochrome P450c17

Additional clinical studies have been carried out in hirsute women with suspected adrenal deficiency of the enzyme 3b -hydroxysteroid dehydrogenase (3b -HSD). This enzyme is common to the adrenal and ovary and women with a putative deficiency should manifest an abnormal ovarian steroidogenic response to nafarelin. The ovarian steroidogenic response to nafarelin in these women did not support the diagnosis of 3b -HSD deficiency. Rather, they were consistent in most cases with polycystic ovary syndrome due to increased activity of cytochrome P450c17.

We have also obtained data which suggest that perinatal exposure of the neuroendocrine axis to excess levels of androgen may program the neuroendocrine system to secrete excessive LH at puberty, thus resulting in ovarian hyperandrogenism. We found that women with congenital adrenal virilization have elevated LH levels at baseline and in response to a test dose of GnRH agonist. These abnormalities are not reversed by glucocorticoid therapy. This "masculinization" of gonadotropin secretion in women appears to depend on the duration and intensity of perinatal androgen exposure.

Finally, we have undertaken studies designed to assess the impact of modulation of insulin resistance on measures of insulin secretion, glucose tolerance, ovarian steroidogenesis, and fibrinolytic capacity. We have studied both metformin and troglitazone. In the case of troglitazone, but not metformin, there is improvement in glucose tolerance, insulin secretion, ovarian androgen excess and inhibition of fibrinolysis.

Genetics of Insulin Secretion and Action in PCOS

We have undertaken studies designed to examine the role of defects in insulin secretion as well as familial factors to the predisposition to NIDDM seen in PCOS. Our current studies are designed to address the following:

To determine if beta cell secretory dysfunction is more prevalent among insulin resistant women with PCOS compared to similarly insulin resistant controls

To determine if first-degree relatives of women with PCOS are at increased risk of a) impaired glucose tolerance or NIDDM; b) insulin resistance; c) beta cell secretory dysfunction

To a) characterize the transmission of beta cell function and insulin sensitivity in families of women with PCOS; b) determine whether the transmission of insulin sensitivity is independent of the transmission of beta cell function; c) characterize the extent to which beta cell dysfunction contributes to the risk imparted by insulin resistance to the development of NIDDM.

Research Papers in PubMed