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

9/24/2018 1

Is it Menopause?

• Age 25 to 40

NAMS 2018

Wendy Wolfman MD FRCS(C) FACOG NCMP Professor Dept. Ob/Gyn University of Toronto Director Menopause Unit Mt. Sinai Hospital Toronto Ontario Canada

Objectives

 1. To review differential diagnosis of secondary

amenorrhoea in young women

 To review etiologies of premature ovarian insufficiency

in this age group

 2. To review clinical impact of premature ovarian

insufficiency

 3. To formulate management options

What’s Wrong with Me?

 32 yr old GOPO-married lawyer LMP 5 mo ago  Was on BCP’s for 15 years. Stopped OCP to give body a

a a rest.

 One period after stopping BCP.  Vaginal dryness and discomfort with intercourse  Sleep is interrupted and she feels hot  She works out 5 days/wk and is 5’5” ,weighs 123 pounds

but gained 5 pounds in the last year

Initial Lab results

 FSH 28  E2 Level 90  TSH 1.5  HgA1C .050  Prolactin 20  AMH <1

Diagnosis?

9/24/2018 2 Most common causes of secondary amenorrhea in women

 1. Pregnancy  2. PCO- FSH-Normal-E2-Normal  3. Hypothalamic amenorrhoea- FSH  E2   4. POI- FSH  E2 

Definition-ESHRE Guidelines 2016

 Clinical syndrome defined by loss of ovarian activity

before 40

 Characterized by amenorrhea or oligomenorrhea for at

least 4 months with raised gonadotropins and low estradiol

 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

 90% present with secondary amenorrhoea  Also known as hypergonadotropic hypogonadism  1% of population <40, 0.1%<30  Results in hypoestrogenism and infertiility  5-10% conceive  Most common cause 90% unknown  As cancer cure rates improve incidence will rise  Modifiable factors-smoking, surgical practice and

modifying medical treatments for malignant and chronic diseases

Nelson L, NEJM 2009 ESHRE Guidelines Hum Reprod 2016

Pathogenesis



20 weeks gestation-6-7 million Primordial germ cells (PGC), 1-2 million at birth, 400,000 at puberty, 500

• vulations in reproductive life

 Fertile lifespan depends on

 size of oocyte pool at birth  rate of depletion over reproductive life  active destruction  possibly inadequate renewal of stem cells

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Early Menopause

 Ages 40-45  3-5% of population  Clinically same risk factors for bone and CVR  HT recommended until average age of menopause or

51-52

Why is the Correct Diagnosis Important

 Huge and serious diagnosis for a young woman

 Prospective Fertility  Long term ramifications of estrogen lack  To Improve symptoms and Quality of Life

Etiology of POI

 Idiopathic most common –up to 90%  Iatrogenic-increasing  Chemotherapy and radiation  surgical  Genetic-10-13%-most Turner’s, in this age group mosaics then

Fragile X (FMR1)- 0.8-7.5% of cases

 Autoimmune-5% of cases  Metabolic- galactossemia  Infectious-HIV, Cytomegalovirus, Zoster, Mumps  Toxins/Environmental-smoking ,organic substances

Yasui JCO 2009 Qin Hum Reprod Update 2015 Hamoda Post Reproductive Health 2017

Informing Patient

 Devastating diagnosis, impairs self-esteem  71% dissatisfied with how they were told  50% saw > 3 clinicians  Need time and information-consider increased risk in relatives  5-10% pregnancy rate  Information re long term health risks  Emotional support  HT does not have same conjectural risks in younger women

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Ramifications of POI

Symptoms



Vasomotor Symptoms



Sleep disturbances



Mood changes and depression



Joint aches



Vaginal Dryness



Sexual Issues-Dyspareunia, Decreased Libido



Dry eyes

Other Issues

 Cardiovascular CHF IHD  Osteoporosis  Earlier neurological problems



Dementia



Strokes



Parkinson’s

 Earlier death

Treatment

 Counselling-untreated reduced life expectancy due to CVR

disease

 relatives may be at increased risk-no predictive tests  Stop smoking  Hormone replacement until average age of menopause-

does not increase breast cancer-need P to protect uterus

 Exercise and weight management  Adequate calcium and vitamin D  Referral to discuss fertility and egg donation if patient is

ready

What is the Best Replacement ?

 Depends on patient and compliance-Individualize  younger patients tend to prefer OCP’s, older HT  Replicate average estrogen level during menstrual cycle 382

pmol/L

 Prefer transdermal therapies with 100μgm estradiol patches

• r 2 mg estrace-Higher doses than menopausal

 12 days sequential (300 mg P or 10 mg provera)- versus

daily P- optimal daily dose for unknown with higher doses of E-

 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

Conclusions

 Suspect POI in young women with secondary

amenorrhoea who are not pregnant

 Prevent POI by preserving ovaries at hysterectomy if

possible

 Hormone therapy in young women does not have the

same risks as therapy in older women

 Treat patients with hormone therapy until the average

age of menopause