Objectives Is it Menopause? 1. To review differential diagnosis of - PDF document

9/24/2018 Objectives Is it Menopause?  1. To review differential diagnosis of secondary -Age 25 to 40 amenorrhoea in young women NAMS 2018  To review etiologies of premature ovarian insufficiency in this age group Wendy Wolfman MD FRCS(C) FACOG NCMP  2. To review clinical impact of premature ovarian Professor Dept. Ob/Gyn University of Toronto insufficiency Director Menopause Unit Mt. Sinai Hospital Toronto Ontario Canada  3. To formulate management options What’s Wrong with Me ? Initial Lab results  FSH 28  32 yr old GOPO-married lawyer LMP 5 mo ago  E2 Level 90  Was on BCP’s for 15 years. Stopped OCP to give body a  TSH 1.5 a a rest. Diagnosis?  HgA1C .050  One period after stopping BCP.  Vaginal dryness and discomfort with intercourse  Prolactin 20  Sleep is interrupted and she feels hot  AMH <1  She works out 5 days/wk and is 5’5” ,weighs 123 pounds but gained 5 pounds in the last year 1

9/24/2018 Definition-ESHRE Most common causes of secondary Guidelines 2016 amenorrhea in women  Clinical syndrome defined by loss of ovarian activity  1. Pregnancy before 40  2. PCO- FSH-Normal-E2-Normal  Characterized by amenorrhea or oligomenorrhea for at  3. Hypothalamic amenorrhoea- FSH  E2  least 4 months with raised gonadotropins and low estradiol  4. POI- FSH  E2   Due to decreased ovarian function  primary ovarian insufficiency or premature ovarian insufficiency  FSH>25 IU/ml on 2 occasions>4 wks apart Diagnosis of POI Pathogenesis  90% present with secondary amenorrhoea  20 weeks gestation-6-7 million Primordial germ cells (PGC), 1-2 million at birth, 400,000 at puberty, 500  Also known as hypergonadotropic hypogonadism ovulations in reproductive life  1% of population <40, 0.1%<30  Fertile lifespan depends on  Results in hypoestrogenism and infertiility  size of oocyte pool at birth  5-10% conceive  rate of depletion over reproductive life  Most common cause 90% unknown  active destruction  As cancer cure rates improve incidence will rise  possibly inadequate renewal of stem cells  Modifiable factors-smoking, surgical practice and modifying medical treatments for malignant and chronic diseases Nelson L, NEJM 2009 ESHRE Guidelines Hum Reprod 2016 2

9/24/2018 Why is the Correct Early Menopause Diagnosis Important  Ages 40-45  Huge and serious diagnosis for a young woman  3-5% of population  Prospective Fertility  Clinically same risk factors for bone and CVR  Long term ramifications of estrogen lack  HT recommended until average age of menopause or  To Improve symptoms and Quality of Life 51-52 Etiology of POI Informing Patient  Idiopathic most common –up to 90%  Devastating diagnosis, impairs self-esteem  Iatrogenic -increasing  71% dissatisfied with how they were told  Chemotherapy and radiation  50% saw > 3 clinicians  surgical  Genetic -10-13%-most Turner’s, in this age group mosaics then  Need time and information-consider increased risk in relatives Fragile X (FMR1)- 0.8-7.5% of cases  5-10% pregnancy rate  Autoimmune -5% of cases  Information re long term health risks  Metabolic - galactossemia  Emotional support  Infectious -HIV, Cytomegalovirus, Zoster, Mumps  HT does not have same conjectural risks in younger women  Toxins/Environmental- smoking ,organic substances Yasui JCO 2009 Qin Hum Reprod Update 2015 Hamoda Post Reproductive Health 2017 3

9/24/2018 Ramifications of POI Treatment  Counselling- untreated reduced life expectancy due to CVR Symptoms Other Issues disease  Vasomotor Symptoms  relatives may be at increased risk-no predictive tests  Cardiovascular CHF IHD  Sleep disturbances  Stop smoking  Osteoporosis  Mood changes and  Hormone replacement until average age of menopause-  Earlier neurological problems depression does not increase breast cancer-need P to protect uterus  Dementia  Joint aches  Strokes  Exercise and weight management  Vaginal Dryness  Parkinson’s  Adequate calcium and vitamin D  Sexual Issues-Dyspareunia, Decreased Libido  Earlier death  Referral to discuss fertility and egg donation if patient is  Dry eyes ready What is the Best Replacement ? Conclusions  Depends on patient and compliance-Individualize  Suspect POI in young women with secondary amenorrhoea who are not pregnant  younger patients tend to prefer OCP’s, older HT  Replicate average estrogen level during menstrual cycle 382  Prevent POI by preserving ovaries at hysterectomy if pmol/L possible  Prefer transdermal therapies with 100 μ gm estradiol patches  Hormone therapy in young women does not have the or 2 mg estrace-Higher doses than menopausal same risks as therapy in older women  12 days sequential (300 mg P or 10 mg provera)- versus daily P- optimal daily dose for unknown with higher doses of  Treat patients with hormone therapy until the average E- age of menopause  Long cycle low dose OCP for contraception or LNG-IUD with estrogen Kaunitz Obste Gynecol 2015 N Am Men Society 2017 Stute P Climacteric 2016 Sassarini Cl Endo and Metab 2015 4