PCOS Treatment and Management Options
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This document provides an overview of polycystic ovarian syndrome (PCOS), including its history, diagnostic criteria, pathophysiology, health risks, infertility issues, and treatment approaches. PCOS is a common endocrine disorder affecting 2-8% of women. It is characterized by irregular periods, excess androgen levels, and polycystic ovaries. Insulin resistance and obesity are strongly associated with PCOS and contribute to its metabolic complications. Lifestyle changes like diet and exercise can help manage symptoms and improve fertility outcomes in many women.
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PCOS Treatment and Management Options
- 1. PCOS Polycystic Ovarian Syndrome Mark Perloe, MD Georgia Reproductive Specialists [email_address] www.ivf.com
- 6. PCO…S Presentation Goldzieher JW, et al: JCEM 22:325, 1962
- 9. Balen et al . Human Repro Update 9:505; 2003
- 12. Ehrmann. NEJM 325:1223; 2005
- 16. Genetic Predisposition Aging Pregnancy Drugs Lifestyle Insulin Resistance Android Obesity ↑ Lipid Storage Hyperinsulinema Altered Fat Metabolism Altered Steroid Hormone Metabolism PCOS : Acne, hirsutism, hyperandrogenism infertility Adapted from Cristello et al . Gynec Endocrin 21:340; 2005
- 20. Adapted from Luque-Ramirez et al . Clinica Chimica Acta Epub 2005 PCOS Insulin-Related Genetic Variants Gene Polymorphism Phenotype IGF-2 Apa l PCOS IGF-IR Trinucleotide repeat Increased fasting glucose and insulin resistance PPAR-У2 Pro12Ala Body mass index Lower insulin resistance PCOS Obesity Lower insulin resistance and hirsutism score Paraoxonase (PON-1) -108C/T PCOS Leu55Met Obesity and insulin resistance SORBS1 Thr228Ala Obesity Calpain-10 UCSNP-43,-19,-63 PCOS and insulin levels UCSNP-43,-45 Hirsutism score and idiopathic hirsutism UCSNP-44 PCOS Adiponectin 45 T/G Androstenedione PCOS Insulin resistance 276 G/I Obesity and insulin resistance Lower adiponectin levels
- 30. Cussons et al . Clin Endocrin (Oxf) 62:289; 2005 Different Diagnosis Gynaecologists Endocrinologists 172 138 Essential Diagnostic Criteria (P<0.001) 61% PCO 81% Androgenization 59% Androgenization 70% Menstrual Irregularity 47% Menstrual Irregularity 47% LH/FSH Ratio Diagnostic Evaluation (P<0.001) 91% Request Ovarian Ultrasound 44% 58% Measure Adrenal Androgens 80% 34% Measure Lipids 67% First Line of Treatment Both used exercise and diet recommendations Infertility Treatment Clomiphene Citrate Insulin Sensitizers
- 51. PCOS Metformin & Ovulation 61 PCOS women with BMI >28 26 women received - Placebo 35 women received - Metformin 1500 mg/day 1 14 28 35 Prog. >25 nmol/L 1 ovulated 14 ovulated P<0.001 Nestler et al. N Engl J Med 1998
- 52. PCOS Metformin & Clomiphene 25 women received - Placebo 2 ovulated P<0.001 Nestler et al. N Engl J Med 1998 21 women received - Metformin 1500 mg/day 19 ovulated CC 50 mg 1 5 10 18
- 60. Adapted from Esinler et al . Fert Steril 84:932; 2005 Embryological and Pregnancy Data Variable PCOS PCO-only Control P Value No. of oocyte-cumulus complexes 15.5 ± 7.3 15.3 ± 6.4 11.7 ± 6.1 <.01 No. of metaphase oocytes 13.4 ± 7.1 13.1 ± 5.6 10.3 ± 5.8 <.01 Metaphase II oocytes/total oocytes (%) 87 86 87 NS 2-pronucleated/metaphase II oocytes (%) 72 67 70 NS No. of 2-pronucleated oocytes 10.1 ± 5.4 9.1 ± 5.2 7.2 ± 4.4 <.01 No. of transferred grade 1 embryos 1.1 ± 0.1 1.0 ± 0.2 0.7 ± 0.1 <.05 No. of transferred grade 1 embryos/no. of 33.3 34.2 24.6 <.05 embryos transferred (%) No. of transferred grade 2 embryos 2.0 ± 0.1 2.1 ± 0.3 2.2 ± 0.1 NS No. of embryos transferred 3.2 ± 1.1 3.2 ± 1.3 3.0 ± 1.2 NS No. of cycles with embryo freezing (n,%) 39 (35.8) 14 (24.1) 64 (28.1) NS Clinical pregnancy rate/embryo transfer (%) 66.0 59.6 44.3 <.05 Implantation rate (%) 28.8 24.3 23.1 NS Multiple pregnancy rate (%) 48 48 41 NS Twin (%) 39 44 34 NS Triplet (%) 9 4 7 NS Miscarriage rate (n,%) 8 (11.8) 9 (33.3) 14 (14.1) <.05 No of OHSS requiring hospitalization (n,%) 4 (3.7) 1 (1.7) 3 (1.3) NS
Notas del editor
- Lecturer introduction and title presentation slide.
- Lecture Synopsis. The objective of this review is to briefly address the current knowledge of diagnosis, cause, complications, and infertility treatment.
- Opening to lecture . Polycystic Ovarian Syndrome was first recognized by Stein and Michael through their Am J Ob Gynec publication in 1935. Since then, this condition is considered to be the most common endocrine disorder of pre-menopausal women, affecting 5% of the population. However, current literature has suggested a higher range of frequency of 5-10%. May ask for feedback from the audience .
- Clarify Abbreviations. Before getting into the details, there are several abbreviations that have been used with regards to PCOS that will be used as part of today’s lecture. Especially looking back into some of the older literature it is important that the terms are defined to separate the structure from the terms used for the condition (change based upon criteria development which will be discussed in the following slides) from the morphology references.
- Review Symptoms and Signs. General criteria and features stated in many review papers including Cristello et al . Gynec Endocrin. 21: 340; 2005 or Ehrmann, NEJM 325:1223; 2005. Franks, Clin Endocrinol. 31:87; 1989 estimate >75%of PCOS women present with anovulatory infertility and 90% with hirsutism. It is important to point out that a single criteria cannot be used alone for clinical diagnosis, plus other endocrine abnormalities (Cushing’s syndrome, thyroid abnormality, hyperprolactinema, etc.) need to be ruled out. May ask audience for features they have noticed in PCOS patients.
- Review Criteria. May bring up debate or controversy of criteria.
- Addition of PCO. As implicated through the addition of the PCO criteria, the ultrasound has provided a large contribution to diagnosis, monitoring and management of PCOS.
- PCO Criteria. Based upon previous literature, the guidelines from the Rotterdam ESHRE/ASRM meeting for polycystic ovaries are provided. It must be reiterated that a women does not have PCOS by having PCO, the “asymptomatic PCO”, other criteria must also be presented and diagnosed.
- Pathogenesis. Regardless that first published descriptions of PCOS date back to the 1930’s, the pathogenesis of PCOS is poorly understood. Briefly review cascade, before in-depth review next slide.
- PCOS Endocrine Cycle. To put the vicious cycle of PCOS in more of a visual context, this diagram has been placed for reference. Include insulin within the description to lead into the next slide.
- Insulin Effects. It has been suggested that the primary defect in PCOS women is insulin resistance. From this table, insulin affects several mechanisms assisting the drive of hyperandrogenism. Increase of first four lines, decrease of IGFBP-1 levels
- Early Signs . With the increase of childhood and teenage obesity in America, recent pediatric literature has asked if PCOS is being misdiagnosed as part of puberty.
- Insulin Effects . Looking at the effects of insulin in a larger scheme, this table adapted from Cristello and colleagues portrays the cascading consequence of life choices, aging and genetics leading to insulin resistance which progresses into other complications including PCOS.
- Early Signs . New research suggests that signs of PCOS including hyperinsulinema maybe be attributed to possibly fetal origins.
- Heritability. Due to the observable trends within families concerning insulin resistance, the question remains whether PCOS has a genetic connection. Franks and colleagues offered the following hypothesis.
- Heritability. As reviewed by Luque-Ramirez and colleagues, multiple single genes have been investigated without a direct linkage to PCOS. However, as Franks et al. stated in the previous slide, the idea that multiple genes are involved has been suggested time and time again.
- Other Complications. As insinuated by the insulin resistance, PCOS is not just a reproductive disorder but a multifaceted metabolic disorder. Review stats given. Obesity is also a feature observed, estimated to effect 50% of PCOS women, classically presented in patients with upper body obesity which has been associated to menstrual disturbances (Hartz et al. Int J Obes. 3:57; 1979). In the older literature, obesity was thought to be the cause of PCOS; it is now understood that obesity is a modifier of the condition. It should also be pointed out that obesity is also considered in some literature to be an environmental factor, i.e. lifestyle.
- Other Complications . Two other areas that have been associated to PCOS patients includes sleep apnea and depression effecting a woman’s productivity and quality of life.
- Other Complications . Due to the high estrogen levels and lack of normal ovulation cycles, there is a risk for endometrial cancer in PCOS women. Refer to stats. Putting into consideration the rates of insulin resistance and obesity together plus the complications of high blood pressure and increased lipids values, PCOS patients are also at risk for cardiovascular disease.
- Reproductive Complications. PCOS not only affects women pre-pregnancy but also post-pregnancy. Several studies have suggested various complications as listed here. Although there is some literature that contradicts a few of these claims such as Haakova et al. Hum Reprod. 18:1438; 2003. May ask for audience feedback.
- Infertility. Franks and colleagues suggested that over 75% of the patients with anovulation were PCOS patients. The anovulation is caused by a hormonal imbalance due to elevated LH levels which drives hyperandrogenism. In the ovary, although primordial numbers are similar to controls, follicular development of the primary follicles is increased in PCOS patients. Yet the ovary is arrested due to the lack of hormone cycling.
- RE vs. Gyn. Left side (green) values represents Gynecologist; right side (blue) values represent Endocrinologist. Mailed questionnaire containing a hypothetical patient’s presentation with obesity, hirutism, oligomenorrhoea and infertility to gynaecologists and endocrinologists in Australia. Data demonstrated differences in essential diagnostic criteria, evaluation tools, and infertility treatment. Concern arises with lack of consensus resulting in varying diagnosis and treatment.
- Weight Loss. Tie in similarity of first line of treatment from previous slide
- The development of obesity and associated insulin resistance involves a multitude of gene products, including proteins involved in lipid synthesis and oxidation, thermogenesis, and cell differentiation. The genes encoding these proteins are in essence the blueprints that we have inherited from our parents. However, what determines the way in which blueprints are interpreted is largely dictated by a collection of environmental factors. The nutrients we consume are among the most influential of these environmental factors. During the early stages of evolutionary development, nutrients functioned as primitive hormonal signals that allowed the early organisms to turn on pathways of synthesis or storage during periods of nutrient deprivation or excess. As single-cell organisms evolved into complex life forms, nutrients continued to be environmental factors that interacted with hormonal signals to govern the expression of genes encoding proteins involved in energy metabolism, cell differentiation, and cell growth. Nutrients govern the tissue content and activity of different proteins by functioning as regulators of gene transcription, nuclear RNA processing, mRNA degradation, and mRNA translation, as well as functioning as posttranslational modifiers of proteins. One dietary constituent that has a strong influence on cell differentiation, growth, and metabolism is fat. The fatty acid component of dietary lipid not only influences hormonal signaling events by modifying membrane lipid composition, but fatty acids have a very strong direct influence on the molecular events that govern gene expression. In this review, we discuss the influence that (n-9), (n-6), and (n-3) fatty acids exert on gene expression in the liver and skeletal muscle and the impact this has on intra- and interorgan partitioning of metabolic fuels.
- Infertility Treatments. Another complicating feature of PCOS is the effects it has on ovulation and fertility. Since there are so many facets to PCOS, there are also multiple options for treating infertility based upon the patient’s characteristics. Although Clomiphene Citrate has demonstrated benefit it should be limited to three cycles (Gysler et al. Fert Ster 37:161; 1982). The infertility industry has developed multiple treatment protocols to offer women with PCOS. The following slides review two studies demonstrating the published success.
- IVF Study. 290 studies were identified, 9 were chosen for the meta-analysis
- IVF Study.
- ICSI Study.
- ICSI Results . *Requires two mouse clicks*. Several outcome parameters were N/S as indicated by the yellow highlight including implantation rates, multiple pregnancy rate and OHSS requiring hospitalization. However, there were several differences including number of oocytes, clinical pregnancy rates/ET, and reduced miscarriage rate that were favorable for the PCOS group (orange highlight).
- OHSS. Due to arrested state of the ovary, overstimulation with gonadotropins can lead to OHSS. Although proper monitoring is key for preventing OHSS, other steps as listed here are also an option.
- Conclusions. PCOS is a multi-faceted condition with various symptoms and features as proven by the changing definition criteria. As reviewed, the effects of PCOS are long-lasting with research questioning the onset during fetal development and insulin resistance that genetically bind women across time. Not to forget the increased risks and relations to cardiovascular disease, endometrial cancer, depression and pregnancy complications potentially effecting a woman’s quality of life. As the most common endocrine disorder in reproductive age women, PCOS also influences a woman’s fertility. However, through the development of countless studies and publications, multiple infertility treatments are available with successful outcomes.