UPDATE: Women s Health Issues Renee B. Alexis, MD, MBA, MPH, FACOG Associate Professor Department of OBGYN Kiran C. Patel College of Osteopathic Medicine
Disclosure of Conflicts of Interest I have no financial relationships to disclose
UPDATE: Women s Health Issues Focus: Hormone Replacement Therapy Today Polycystic Ovarian Disease Diagnosis and management
UPDATE: Women s Health Issues Objectives Update the new definition of PCOS Review options for treatment of patients with PCOS Review the findings of long term follow-up of the WHI study from 2002 Discuss new management options in treating menopausal symptoms
Polycystic Ovarian Disease Definition: Traditional NIH (1990) Clinical or biochemical hyperandrogenism Ovulatory dysfunction Exclusion of other androgen excess disorders Rotterdam Consensus (2003): 2 of the following Clinical or biochemical hyperandrogenism Ovulatory dysfunction Polycystic ovaries on ultrasonography Exclusion of other androgen excess disorders Different for adolescents
Polycystic Ovarian Disease Androgen Excess and PCOS Society Required androgen excess Plus Ovulatory dysfunction or PCOS ovaries or both
Polycystic Ovarian Disease UPDATE: Defining and diagnosing PCOS In 2012 NIH sponsored evidence based workshop Outcome: Use the Rotterdam 2003 criteria for diagnosing PCOS Specify Phenotype Recommended renaming the disease given PCO are not a necessary finding for diagnosis Prevalence of PCOS increased up to 20.9%
PCOS Phenotypes
Polycystic Ovarian Disease UPDATE : Phenotypes and Disease Risk Women with ovulatory dysfunction and PCO without excess androgens have the lowest risk for diabetes mellitus Therefore important to record phenotype for clinical care UPDATE: Insulin resistance/diabetes and PCOS Measuring insulin levels not necessary for diagnosing or management of PCOS Fasting blood glucose inadequate for diagnosing diabetes in women with PCOS; 2hrOGTT recommended in all women with PCOS
Polycystic Ovarian Disease UPDATE Unlike metabolic syndrome, it is uncertain if PCOS is an independent risk factor for CV disease Large scale prospective trials needed to further elucidate of CV development Similar to diabetes risk of CV disease may be phenotype specific
Polycystic Ovarian Disease Management Depends on clinical manifestations and desires of the patient
Polycystic Ovarian Disease UPDATE: Management Modest weight reduction 5-10% improves insulin resistance and improves reproductive features No specific diet is better over another Reduce caloric intake 150 min of exercise (aerobic) per week Even prevention of additional weight gain is important Target women with BMI >25
Polycystic Ovarian Disease UPDATE: Management Oral estrogen-progestin pills (OEP) Reduces LH which decreases ovarian androgen production Increased SHBG which decreases free testosterone levels Reduced endometrial hyperplasia Best OEP for those with acne are those with less androgenic progestin (FDA approved: Drospirenone, desogestrel, norgestimate and norethindrone acetate) Contraindications to OEP Oral progestin (norethindrone acetate 5 mg daily) Levonorgestrel IUD
Polycystic Ovarian Disease UPDATE: Management Problem with OEP: OEP does not improve insulin resistance or reduce fat secretion of adipokines OEP does not block androgen at the level of the skin Recommendation for dual therapy Metformin Spironolactone
Polycystic Ovarian Disease UPDATE: Management OEP plus Metformin in women with insulin resistance In some trials OEP and metformin 1,500mg daily led to greater increase in SHBG than OEP alone Also weight loss and reduction of waist to hip ratio occurred only in patients with OEP plus metformin group Consider OEP plus metformin in patients that have BMI >30 kg/m 2 Waist-to-hip ration > 0.85 Acanthosis Nigrans History of gestational diabetes, family history Diagnosis of metabolic syndrome
Polycystic Ovarian Disease UPDATE: Management Spironolactone with OEP for women with hirsutism Spironolactone adds to the effect of reduced LH from OEP A few small trials have demonstrated better treatment of hirsutism with OEP plus spironolactone vs. OEP mono-therapy
Polycystic Ovarian Disease Ovulation Induction Management Clomiphene citrate SERM FDA approved for ovulation induction Resistance can be observed Letrozole aromatase inhibitor not FDA approved for ovulation induction
Polycystic Ovarian Disease UPDATE: Management Ovulation Induction Progestin withdrawal not necessary before increasing clomid does; may actually reduce live births Stepwise increase in clomid dose can reduce time to ovulation Clomid with metformin and clomid alone have similar live birth rates but better than metformin alone When compared to clomid, letrozole had significantly more live births Letrozole may be the preferred ovulation induction therapy in patients with PCOS especially in those women who display resistance to clomid
Polycystic Ovarian Disease UPDATE Evaluate for emotional well being and refer for appropriate treatment Recognition of anxiety and depression remains low and prevalence is high (30%) Mood disorders may affect women with PCOS and treatment of disease.
Hormone Replacement Therapy The importance 31.3 million postmenopausal women by 2010 consensus 2million women per year enter menopause Life expectancy is increasing currently 81 years Hormone Therapy prescribed since the 1960s Initially for menopausal symptoms Shifted to menopause and a preventable disease
Hormone Replacement Therapy UPDATE: Terminology Ovaries age at different rates in different women In 2012 updated Stages of Reproductive Aging Workshop (STRAW+10) Divides reproductive aging into 4 stages Reproductive stage Menopausal transition Early postmenopausal period Late postmenopausal period Characterized by menstrual cycle
Hormone Replacement Therapy 1997 Postmenopausal estrogen/progestin Intervention Trial Evaluated HRT and CV disease markers Favorable effects o lipids 1998 the Heart and Estrogen/Progestin Replacement Study No favorable benefit of HRT in prevention of CV disease
Hormone Replacement Therapy In 2002 Women's Health Initiative (WHI) Estrogen plus Progestin Trial results Stopped early 5.2 years of follow up Increased risk of CV disease Increased breast cancer risk Decreased risk of colon cancer Decreased risk of hip fracture
Hormone Replacement Therapy Women's Health Initiative (WHI) (con t) Estrogen alone therapy Increased stroke and thromboembolic events No increase in CV disease risk No increase in breast cancer risk Decreased risk of hip fracture
Hormone Replacement Therapy Given that the increase in breast cancer was seen in the EPT arm of the study there is concern that it may very well be the type of progestin that increase the risk of breast cancer with systemic HT
Hormone Replacement Therapy WHI long term follow up 2013 report from WHI Systemic HT safe to initiate women younger than 60 years of age and less than 10 year since onset of menopause Cumulative 18 year follow-up (both ET and EPT) Systemic HT did not increase all cause mortality (even with stratifying bay age) Systemic HT did not increase cause specific mortality All cancer mortality CV mortality
Hormone Replacement Therapy WHI long term follow-up (con t) Breast cancer mortality EPT risk was 1.44 ET risk was 0.55
Hormone Replacement Therapy WHI in review Generalizability is limited with use of other HT preparations Different routes were not assessed Different types of progestational agents were not evaluated Many subgroups and many outcomes were evaluated in this one study which limits interpretation of HT and cause specific mortality.
Hormone Replacement Therapy UPDATE The cumulative follow up of the WHI study and no increase in all cause mortality is important for assessing safety of systemic HT 5-7 years North American Menopause Society (NAMS) and the Endocrine Society agree that HT is a viable option for treating menopausal women with moderates to severe symptoms
Hormone Replacement Therapy UPDATE Novel Preparations of systemic HT FDA approved SERM Bazodoxifene with conjugated estrogen Reduce vasomotor symptoms of menopause without increasing risk of endometrial cancer No increase in myocardial infarction thromboembolic disease
Hormone Replacement Therapy Bio identical hormones Estrogen and progesterone that is chemicals that are compounded and is identical to those produce in the body )E2 and progesterone) Often reported to be safer and more effective than commercial preparations Claims of slowing the aging process Claims that they deliver customized dose Saliva testing is performed to evaluate circulating hormone level
Hormone Replacement Therapy UPDATE Bio Identical hormones No research has shown that they are superior to commercially available preparations Has not been shown to be safer than other available systemic HT preparations Customized compounding may have limited quality control untested purity and may vary from batch to batch Difficult to customized dose because a woman's hormone levels vary from day to day
Hormone Replacement Therapy UPDATE Bio Identical hormones (con t) Saliva testing is expensive and not needed for starting hormonal therapy Compounded progesterone products may not result in sufficient amount to protect the uterine lining
Hormone Replacement Therapy Determining reproductive aging is important since it helps to make the diagnosis of conditions and guide treatment options
Hormone Replacement Therapy UPDATE HT is safe to give to postmenopausal women for moderate to severe vasomotor symptoms or vulvo-vaginal symptoms 2012 Cochrane review of randomized double blind placebo controlled trials of HT Supports HT not for use to prevent CV disease or dementia Similar findings of WHI study including increase risk of GB disease Over 65 had increased risk of dementia
Hormone Replacement Therapy UPDATE (Con t) Characteristics to start systemic HT Younger than 60 Less than 10 years since last menstrual period No history of major risk factors such as CV disease, stroke, DVT/PE, breast cancer abnormal vaginal bleeding Lowest dose shortest amount of time Recommended those in early or premature menopause would likely benefit from HT until at least natural menopause age Symptom relief Maintain BMD Possible reduction in risk of CV disease
Hormone Replacement Therapy Routes of administration Oral Transdermal intravaginal Options include Systemic HT Bazodoxifene plus estrogen therapy Vaginal/local estrogen Low dose paroxetine
Updates: Women's Health Issues Conclusion PCOS PCOS is a dynamic disease not only in its phenotypes but also in its definition and management PCOS impacts the health of women significantly and has a high disease burden Define PCOS based on it phenotypes to direct appropriate treatment Consider adding metformin and spironolactone or both to OEP to better manage patient symptoms Letrozole is better at ovulation induction than clomid
Updates: Womens Health Issues HRT Systemic HT is still a safe and viable option for treatment of women who have moderate to severe menopausal symptoms HT is should not be prescribed as a preventative medication Evidence has shown that for women with premature menopause or menopause before age 45 y/o, systemic HT may reduce the risk of CV disease and associated morbidity and mortality Bioidentical hormones can be expensive and have no better efficacy or safety than commercial preparations. In addition, compounded progesterone may be substandard in protecting the uterine lining Transdermal preparations may offer lower risk of thromboembolic disease
References 1, Hoger MD, Kathleen and Vitek, Wendy. Polycystic ovarian disease. Clinical Updates in Women s Healthcare. Volume XV, Number 4, July, 2016. 2. Shifren MD, Jan L. and Schlam Eldelman, MD, Julia. Hormone therapy and alternative therapies for menopause. Clinical Updates in Women s Heathcare. Volume XIV, Number 4, October, 2015. 3. Barbieri, Robert. Treating Polycystic ovary syndrome: Start using dual medical therapy. OBG Management. April 2017;29(4);8-10, 12-13. 4. Kaunitz MD, Andrew. Did long term follow-up of WHI participants reveal mortality increase among women who received HT?