Laboratory of Endocrine and Metabolic Health
Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in women, affecting approximately 1 in every 10 women. PCOS impacts the hormone, metabolic, reproductive, and psychological health of women. Despite its prevalence and impact on female health, the cause of the disorder remains unknown. Diagnosis is made by the presence of at least two of the three features of (1) hyperandrogenism (clinical or biochemical), (2) menstrual irregularity (due to oligo-ovulation or anovulation), and/or (3) polycystic ovaries, as well as the exclusion of other endocrine disorders as a cause of these features. Other common findings in women with PCOS include hyperinsulinemia and insulin resistance, increased incidence of obesity and obesity-related morbidities such as diabetes and cardiovascular dysfunction, subfertility, greater incidence of miscarriage, hirsutism, acne, depression, and anxiety. Current treatment options are limited to addressing individual symptoms associated with PCOS, as the cause of the disorder remains elusive.
The mission of the Laboratory of Endocrine and Metabolic Health is to conduct research that will further elucidate the mechanisms underlying the endocrine and metabolic alterations that occur in women with PCOS and to investigate alternative, non-pharmacologic treatment options for these women. This research will help us better understand the etiology and pathogenesis of the disorder, which is essential for the development of more targeted therapies in the future. In addition, identification of alternative or complementary treatment modalities for women with PCOS will provide more therapeutic options for women who desire a non-pharmacologic approach to managing the symptoms associated with PCOS.
Our research group is currently pursuing three major goals:
- Determine the impact of non-pharmacologic interventions on the endocrine, metabolic, and psychological health of women with PCOS.
The cause of PCOS remains unknown, and as a consequence, the treatment options available to women with PCOS are limited to addressing individual symptoms. Often times, this involves the use of medication, such as hormonal contraceptives to regulate the menstrual cycle or ovulation inducers if pregnancy is desired. The effectiveness of such medications may vary, and can include a number of unwanted side effects. Non-pharmacologic approaches to manage the symptoms with PCOS are desirable, as they have the potential to provide therapeutic options with limited or no unwanted side effects. Such approaches could be used as alternatives or complementary to existing treatment options.
Yoga is a low-impact exercise that is accessible to individuals of varying fitness levels and who may be uncomfortable with more intense aerobic activity. Yoga practice promotes mindfulness, and encompasses the osteopathic principles of the body as a unit, which is capable of self-healing. As a holistic exercise, it is also ideal for reinforcing awareness of the body’s posture and breathing, common to both mindfulness and osteopathic body awareness training. One of the goals of our research is to determine the effect of regular yoga practice on the endocrine, metabolic, and psychological health of women with PCOS. Our hypothesis is that yoga practice 3 times per week for 3 months will improve androgen levels, metabolic health, and anxiety and depression in women with PCOS.
Osteopathic manipulative treatment (OMT) is a powerful, non-pharmacologic tool for treating patients with a number of different ailments. OMT has been used to modulate activity of the sympathetic nervous system (SNS) in healthy patients, and may be effective in treating patients with PCOS who often have SNS hyperactivity. Another goal of our research is to determine the effect of weekly OMT on the endocrine, metabolic, and psychological health of women with PCOS, as well as sympathetic tone in these women. Our hypothesis is that weekly OMT for 3 months will improve sympathetic tone, androgen levels, and anxiety in women with PCOS.
Together, this research will help determine the effectiveness of non-pharmacologic interventions in the treatment of women with PCOS, and could provide alternative or complementary therapeutic options for women with PCOS.
- Examine changes in the adipose and other insulin-sensitive tissues in an animal model of PCOS.
Hyperandrogenism is a critical component and feature of PCOS, and there is strong evidence to support that it plays a role in both the development and exacerbation of PCOS presentation. In particular, prenatal exposure to androgens contributes to the development of PCOS, and is a widely-used model for studies of PCOS in animals. Our laboratory uses a prenatally androgenized (PNA) rat model for PCOS, which exhibits many of the endocrine, metabolic, and reproductive features associated with PCOS in women.
There is a reciprocal relationship between androgens and insulin in women with PCOS, where an increase in one can stimulate an increase in the other. Greater serum levels of each are associated with more severe reproductive and metabolic outcomes in women with PCOS. Insulin resistance is reported to be intrinsic to PCOS, independent of obesity, and it quadruples the risk of developing type 2 diabetes (T2D). In T2D, insulin signaling pathway components are reported to have lower levels of protein expression and activity, which contributes to insulin resistance. One of the goals of our research is to characterize the changes in insulin signaling in the insulin-sensitive tissues of PNA rats compared to control rats. Our hypothesis is that the insulin-sensitive tissues of adult PNA rats will exhibit reductions in protein expression and activity of components of the insulin signaling pathway as compared to the same tissues in control rats. In addition, we will compare serum insulin levels in adult PNA rats to those in control rats, and compare these findings to the observed alterations in insulin signaling pathway components in the same animals.
Obesity is a common finding in women with PCOS, and the endocrine, reproductive, and metabolic features of PCOS are further exacerbated by the presence of obesity. This exacerbation may be due, in part, to the altered function of adipose tissue in obesity. Another goal of our research is to characterize the changes in adipose tissue function in PNA rats compared to control rats. Our hypothesis is that the adipose tissue in adult PNA rats will exhibit dysfunction that correlates with the development of obesity in these animals compared to control rats.
Together, this research will help us to better understand the molecular changes associated with the insulin resistance and obesity components of PCOS in a rodent model for the disorder. Providing insight into these mechanisms may lead to better, more targeted therapeutic options for patients with PCOS and diabetes in the future.
- Examine the effects of androgen excess on lipid storage and insulin signaling in a cell culture model.
Hyperandrogenism is a key feature of PCOS, and is reported to be critical in the development and exacerbation of PCOS. As many women with PCOS-related hyperandrogenism also suffer from obesity, it is important to determine the effects of elevated levels of androgens on adipose function. To investigate the role of androgens on adipocyte function, we employ a cell culture model in which preadipocytes are differentiated into adipocytes in the presence or absence of androgens, at concentrations similar to those found in the serum of women with PCOS. This model allows us to focus on one cell type, under controlled conditions, to examine the effects of androgens on adipocytes. Our hypothesis is that androgens, at concentrations similar to those found in women with PCOS, will promote adipocyte dysfunction and altered lipid storage. This model is also conducive to investigating the effects of combinations of hormones or hormones and compounds on adipocyte function, including compounds that may be of therapeutic use in attenuating the development of obesity.
This research allows us to better understand the role of androgens on adipocyte function, which may provide insight into the development of obesity in women with PCOS.
Exposure to androstenedione alters lipid storage in mature adipocytes. 3T3-L1 adipocytes were differentiated in the absence (left, vehicle only) or presence (right) of androstenedione for 10 days, at which time mature adipocytes are present. The lipid content of the adipocytes was stained with oil red O (red in the image) to allow for comparisons between control and androstenedione-exposed adipocyte storage. Note that the androstenedione-exposed adipocytes are smaller in size but greater in number compared to a similar field of control adipocytes.