Addressing Practice Gaps in PCOS PCOS Challenge September 21, 2014 Ricardo Azziz, MD, MPH, MBA President, Georgia Regents University CEO, Georgia Regents Health System
Introduction PCOS research began in 1935 with initial description by Irving Stein and Michael Leventhal More recent years, whole-hearted debates have ensued However, significant practice gaps in evaluation and treatment still remain Poor understanding of current literature Varying needs and presentations of patients Variable diagnostic resources Deficits in available science
Current Practice Gaps In evaluating patients with possible PCOS: Who should be assessed? What does PCOS look like anyway? What criteria for PCOS to use? What constitutes minimal evaluation? What is normal?
Current Practice Gaps In counseling patients with PCOS: What is the course of the disorder in adolescence or into menopause? What are the vascular, cardiovascular disease (CVD), and neoplastic risks in PCOS? Is there a male phenotype of PCOS?
Current Practice Gaps In treating PCOS patients What are the optimum means of weight loss and/or weight maintenance? What is the optimum therapy for the dermatologic symptoms of the syndrome, including hirsutism and androgenic hair loss? When to and how often to assess for metabolic dysfunction?
Evaluating Patients with Possible PCOS Who should be assessed for possible PCOS? Data suggests two major features may be sufficient to identify PCOS Signs & complaints consistent with clinical hyperandrogenism (alopecia, persistent acne, and excess male-like terminal hair growth History & complaints suggestive of ovulatory dysfunction
Evaluating Patients with Possible PCOS What does PCOS look like? The way we see PCOS influenced by: What drives patients to see a care provider (referral/selection bias) What kind of practitioner sees the patient (perception/information bias) The knowledge base of the practitioner (information bias)
Evaluating Patients with Possible PCOS What criteria for PCOS to use? Currently three sets in use National Institute of Health (NIH)1990 criteria European Society for Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM) (also called Rotterdam) 2003 criteria Androgen Excess & PCOS Society (AE-PCOS) 2006 criteria
Comparing the Phenotypes of PCOS by NIH 1990, Rotterdam 2003, and AE-PCOS 2006 Phenotypes Characteristics A B C D Hirsutism/HA Ovulatory Dysfunction Polycystic ovaries NIH 1990 Rotterdam 2003 AE-PCOS 2006
Evaluating Patients with Possible PCOS What criteria for PCOS to use? Both Rotterdam 2003 and AE-PCOS criteria are expansions of the original NIH 1990 criteria All three sets view PCOS as diagnosis of exclusion Specific criteria used often on: The practice focus of the practitioner The desired outcome (fertility, suppression, long-term care, etc.) The tools available to the patient/practitioner
Evaluating Patients with Possible PCOS What constitutes minimal evaluation? When to assess androgens? Which androgens? Using what types of assays? When to assess ovaries? How? Do all hirsute eumenorrheic women require assessment of ovulation? 1, 2, or 3 months? Recommended course of evaluation often varies according to availability of diagnostic resources
LABORATORY EVALUATION OF THE HIRSUTE OR POTENTIALLY HYPERANDROGENIC PATIENT 17-HP To R/O 21-OH deficient NCAH TSH & PRL In oligo-ovulatory patients, to R/O other causes of ovulatory dysfunction Total & free T, and DHS In non-hirsute, minimally hirsute, or acneic oligoovulatory patients, to R/I Androgen Excess Day 22-24 P4 level In hirsute eumenorrheic women, 10-40% of which are anovulatory
Evaluating Patients with Possible PCOS What constitutes minimal evaluation? Much can be learned from epidemiologic trials identifying PCOS in unselected populations: Hirsutism w/ Oligomenorrhea: Need to exclude related/similar disorders only (TSH, Prl, 17-HP, clinical history and exam) Hirsutism w/o Oligomenorrhea: Assess ovulation with d. 22-24 P4 level (in all three criteria) or ovarian morphology (in AE- PCOS/Rotterdam); if abnormal then exclude related/similar disorders Oligomenorrhea w/o hirsutism: Assess androgen levels (in all three criteria) or ovarian morphology (in Rotterdam only); if abnormal then exclude related/similar disorders
Evaluating Patients with Possible PCOS What is normal? Understanding what is abnormal critically depends on knowing what is normal How do you define the normal cut-off value? Need to potentially consider age, degree of obesity, race, ethnicity, and so on DHEAS vs. age mfg vs. ethnicity
Counseling Patients with PCOS What is the course of the disorder in adolescence or into menopause? Very little known about PCOS in: Childhood Adolescence Adult women as they approach and enter menopause
Counseling Patients with PCOS What are the vascular, cardiovascular (CVD) and neoplastic risks in PCOS? Much is known about risk of diabetes in PCOS Much less is known about the vascular, CVD, and cancer risks of PCOS, particularly controlling for cofounders, such as weight, race, and socioeconomics
Counseling Patients with PCOS Is there a male phenotype of PCOS? Many of the genetic variants present in PCOS women will also be present in their male relatives The variants directly determining the hyperandrogenic features of PCOS may have little impact in males The genetic traits determining associated metabolic and vascular dysfunction may be of significance in affected men
Treating PCOS Patients What are the optimum means of weight loss and/or weight maintenance? It is clear that overweightness and obesity is a concern for many women with PCOS However, the optimum diet/exercise for weight loss and/or maintenance is unclear: Hi Protein/Normal Protein? Lo Carb/Normal Carb? All the same? Different for different patients? Only for obese patients? Is IR predictive of response? Do PCOS patients gain weight more easily or have greater difficult losing weight than women of similar weight without PCOS?
Treating PCOS Patients What is the optimum therapy for dermatologic symptoms of PCOS, including hirsutism and androgenic hair loss? Initial multi vs. single therapy for hirsutism? Is antiandrogen therapy able to transform androgen-sensitive terminal hairs to vellus hairs? What is the actual risks of SPA and Flutamide in young women with PCOS Does OCP therapy worsen the risk of DM in PCOS? And we are the novel therapies for PCOS?
Treating PCOS Patients When to and how often do we need to assess metabolic dysfunction? Well documented that many women with PCOS will be at increased risk for metabolic dysfunction Less well documented is what tests, in whom, and who often should be reassessed Lipids initially? How often do we repeat? ogtt initially for all? How often do we repeat? On or off therapy? Insulin during ogtt?
THE ECONOMIC BURDEN OF PCOS IN THE U.S. IS AT LEAST 4 BILLION DOLLARS ANNUALLY: Attributable Care Provided During The Reproductive Years Only Annual costs (in millions) % of total costs For Initial Evaluation 99 2.3 For Treatment Menstrual dysfunction 1,350 30.9 Infertility 533 12.2 Type 2 DM 1766 40.4 Hirsutism 622 14.2 Total 4,370 100 Azziz et al. J Clin Endocrinol Metab 90: 4650, 2005
Conclusion Addressing these and other practice gaps will require significant resources and the dedication of a coalition, including: Patients and patient advocacy groups, e.g. PCOS Challenge Government agencies (FDA, NIH) Researchers and clinicians, and their associated organizations (e.g. AE-PCOS Society, Endocrine Society) Corporate and industry partners
Thank You