7/2/18 OBJECTIVES MENOPAUSE • To describe risks of HT by age and menopause onset WHAT’S NEW? WHAT’S SAFE? • To recommend specific HT regimen for women who undergo early menopause and who undergo menopause at the expected time Sara W hetstone, MD HT –Hormone therapy ET –Estrogen only therapy EPT –Estrogen-progestin therapy GLOSSARY CEE –Conjugated equine estrogen MPA –Medroxyprogesterone acetate MP –Micronized progesterone 1
7/2/18 PB is 66yo G0 woman who PB is 66yo G0 woman who CONSEQUENCES OF EARLY MENOPAUSE AND underwent bilateral underwent bilateral PRIMARY OVARIAN INSUFFICIENCY oophorectomy at age 40 after oophorectomy at age 40 after her sister was diagnosed with her sister was diagnosed with ovarian cancer. She was ovarian cancer. She was started on HRT for very started on HRT for very bothersome hot flashes. She bothersome hot flashes. She V asom otor Bone loss and Increased heart G SM sym ptom s osteoporosis disease presents to discuss continuation presents to discuss continuation of HRT. She is currently taking of HRT. She is currently taking PO conjugated equine estrogen PO conjugated equine estrogen Dem entia and Depression and Higher overall cognitive anxiety related (CEE) and continuous (CEE) and continuous m ortality decline disorders medroxyprogesterone acetate medroxyprogesterone acetate (MPA). (MPA). Vasomotor symptoms INDICATIONS MANAGEMENT OF EARLY MENOPAUSE FOR HT Prevention of bone loss (FDA-APPROVED) q Hormone replacement Estrogen therapy • Dosage higher than usual q Exercise post-menopausal ET Hypoestrogenism q Healthy diet • Monitoring estradiol levels (caused by hypogonadism, oophorectomy, or POI) q Adequate calcium and NOT recommended vitamin D intake Progestin necessary if patient Genitourinary syndrome of q Avoidance of smoking has intact uterus menopause (GSM) (or vulvo-vaginal atrophy) 2
7/2/18 PB is 66yo G0 woman who PB is 66yo G0 woman who underwent bilateral underwent bilateral oophorectomy at age 40 after oophorectomy at age 40 after her sister was diagnosed with her sister was diagnosed with ovarian cancer. She was ovarian cancer. She was started on HRT for very started on HRT for very bothersome hot flashes. She bothersome hot flashes. She presents to discuss continuation presents to discuss continuation of HRT. She is currently taking of HRT. She is currently taking PO conjugated equine estrogen PO conjugated equine estrogen (CEE) and continuous (CEE) and continuous medroxyprogesterone acetate medroxyprogesterone acetate RECOMMENDED TREATMENTS (MPA). (MPA). ACOG Committee Opinion, 2017. Estrogen replacement COMMON HT REGIMENS • Transdermal recommended (over oral) • Can also use vaginal ET • Lower risk of VTE CHOOSING • Rovinski D (2018): Oral HT was WHICH REGIMEN associated with increased risk of VTE, while non-oral HT was not TO PRESCRIBE • Lower risk of stroke • Lower risk of hypertriglyceridemia Bottom Line : Start with transdermal estrogen patch (17-beta estradiol) 3
7/2/18 BREAST & CV EFFECTS OF PROGESTINS Progestin therapy § Recommendation for oral micronized progesterone (MP) CHOOSING WHICH REGIMEN § Sequential: 200mg/day x 12 days per month TO PRESCRIBE § Continuous: 100mg daily Llaneza P, Gynecol Endocrinol, 2018. D is a d v a n ta g e s Using LNG -IUS for endometrial (1 ) H ig h e r d o se o f E + P protection would be considered an off- th e ra p y label use (2 ) ? in fe rio r to h ig h e r d o se H T in re g a rd s to B M D Reasonable to consider in women who WHAT ABOUT do not tolerate oral progestins WHAT ABOUT LEVONORGESTEREL Can be utilized by women who desire OCPS? IUD? ET at non-contraceptive levels and who are still at risk of pregnancy Effective for endometrial protection for A d v a n ta g e s peri-menopausal and post-menopausal (1 ) E a sie r to u se , le ss stig m a women using ET (2 ) O ffe rs c o n tra c e p tio n 4
7/2/18 PB is 66yo G0 woman who PB is 66yo G0 woman who Should PB stop HT? underwent bilateral underwent bilateral WHEN TO STOP HORMONE REPLACEMENT? 1) Yes oophorectomy at age 40 after oophorectomy at age 40 after 2) No her sister was diagnosed with her sister was diagnosed with 3) It depends… ovarian cancer. She was ovarian cancer. She was § Treatment for women with primary ovarian insufficiency/early started on HRT for very started on HRT for very menopause should continue until the average age of natural bothersome hot flashes. She bothersome hot flashes. She menopause (50–51 years) presents to discuss continuation presents to discuss continuation § Treatment may continue past age 50–51 years if a woman has of HRT. She is currently taking of HRT. She is currently taking clinical symptoms or indications. PO conjugated equine estrogen PO conjugated equine estrogen § Regardless of age, the decision to continue HT should be (CEE) and continuous (CEE) and continuous individualized and based on a woman’s symptoms and the risk– medroxyprogesterone acetate medroxyprogesterone acetate benefit ratio. (MPA). (MPA). WHEN TO STOP? Extended use m ay benefit w om en for relief of VM S, prevention of bone loss and fracture, and treatment/prevention of G SM “APPROPRIATE DOSE, V asom otor sym ptom s recur in 50% of w om en DURATION OF “LOWEST DOSE FOR DURATION, REGIMEN, THE SHORTEST PERIOD TREATMENT M any of the benefits/risks of HT do not persist beyond 5 to 7 years AND ROUTE OF OF TIME” Ele va te d (b ut ra re a b so lute risk) o f b re a st ca nce r w ith C EE + M PA in m e d ia n 1 3 y r ADMINISTRATION fo llow -up C V D risk b e ca m e ne ura l B o ne p ro te ctio n ra p id ly d issip a te s a fte r H T d isco ntinua tio n S ig nifica nt re d uctio n in b re a st ca nce r w ith C EE d uring 1 3 ye a r fo llow -up PRIOR GUIDING PRINCIPLE CURRENT GUIDING PRINCIPLE A ll-ca use m o rta lity w a s ne utra l in C EE + M PA g ro up in 1 3 ye a r fo llow -up Data lacking on benefits/risks of longer duration and w ith discontinuation of HT 5
7/2/18 OUR ADVICE FOR PB: TG is a 64yo woman who underwent menopause at age 49. § Recommend discontinuation of HT She has noticed increased joint stiffness and prolonged fatigue after exercising in the last 18 § If PB is hesitant to stop HT or has recurrent bothersome menopausal months. She was encouraged by symptoms, would recommend her PCP to present to GYN to § Trying non-hormonal treatments § Switching to transdermal estrogen discuss initiating hormone § Switching to micronized replacement therapy for her progesterone symptoms. Her medical history is § Lowering dose as tolerated notable for hypertension and § Reassessing HT on an annual basis hyperlipidemia. TG is a 64yo woman who JOINT PAIN AND HT underwent menopause at age 49. She has noticed increased joint § E v id e n c e o f e stro g e n b in d in g to e stro g e n stiffness and prolonged fatigue re c e p to rs o n jo in t tissu e s after exercising in the last 18 § In c o n siste n t e v id e n c e a b o u t e ffe c ts o f E T o n months. She was encouraged by o ste o a r th ritis a n d a r th ra lg ia § M a y b e b e n e fits o f e stro g e n a n d S E R M s o n jo in t her PCP to present to GYN to p a in Would you start discuss initiating hormone § In W H I: replacement therapy for her TG on HT? § W o m e n o n C E E + M PA (v s p la c e b o , 4 7 .1 % v s symptoms. Her medical history is 3 8 .4 % ) h a d le ss jo in t p a in / stiffn e ss, m o re 1) Yes notable for hypertension and d isc o m fo r t w h e n sto p p in g H T § W o m e n o n C E E h a d sta tistic a lly sig n ific a n t le ss hyperlipidemia. 2) No jo in t p a in (v s p la c e b o , 7 6 .3 % v s 7 9 .2 % ) 3) Maybe 6
7/2/18 Potential risk Age and/or time from menopause onset <60 years or <10 years from >10 years from menopause menopause Coronary heart Potential for increased risk Reduced risk of CHD disease of CHD All-cause Significant reduction in all-cause RISKS OF No protective effect of HT mortality mortality HT BY AGE Meta-analysis of RCTs : No Meta-analysis of RCTs : increased risk of stroke Increased risk of stroke Stroke Observational studies : mixed Rare risk but significantly VTE Higher absolute risk increased with HT SUMMARY OF HEALTH RISKS OF HT BY AGE AND/OR TIME FROM MENOPAUSE ONSET Manson JE, JAMA 2013. NAMS ALGORITHM CVD RISK AND TIME SINCE MENOPAUSE ONSET Manson JE, Menopause, 2015. 7
7/2/18 BP is a 52yo woman who “For women who initiate HT cannot sleep due to her hot more than 10 to 20 years flashes. Her last period was approximately 8 months from menopause onset or ago. She is miserable. She when aged 60 years or older, is interested in exploring HT the benefit-risk ratio appears but worried specifically less favorable than for younger women because of about risks of HT. In the past, she has had really bad greater absolute risks of CHD, experiences with progestin stroke, VTE, and dementia.” therapy. 2017 HT Position Statement of NAMS TREATMENT OF VASOMOTOR SYMPTOMS Vasomotor symptoms INDICATIONS Most effective treatment: systemic hormone therapy (HT) with estrogen therapy FOR HT Prevention of bone loss (FDA-APPROVED) If u te r u s p re se n t... If u te r u s a b se n t… Hypoestrogenism (caused by hypogonadism, oophorectomy, or POI) Genitourinary syndrome of menopause (GSM) E s tro g e n + P ro g e s tin E s tro g e n a lo n e (or vulvo-vaginal atrophy) (E P T ) (E T ) 8
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