Physiology of Menopause Timothy Rowe University of British Columbia - PowerPoint PPT Presentation

Physiology of Menopause Timothy Rowe University of British Columbia 16th WCM 6/4/18 21 Pre-Congress Workshop

I have received consulting fees and honoraria for speaking from Pfizer Canada Inc. I have no other competing or potentially competing interests 16th WCM 6/4/18 22 Pre-Congress Workshop

Wh What I want to talk about • Apoptosis and the ovary • Endocrine changes • Neurological changes • Bone and joint changes • Urogenital changes • Cardiovascular changes 16th WCM 6/4/18 23 Pre-Congress Workshop

Ov Ovarian res eser erve e fr from om con oncep eption on to o men menop opause Wallace WH, Kelsey TW. PLoS One 2010 Jan 27;5(1):e8772. 16th WCM 6/4/18 24 Pre-Congress Workshop

Apo Apoptosi sis s and nd ovarian n rese serve • During fetal life, apoptosis primarily involves the oocyte • After birth, and in adult life, it involves primarily follicular granulosa cells, although oocytes in primordial follicles may also be affected • 99.9% of follicles present at birth never reach the stage of ovulation, but undergo atresia • The reduction in oocyte complement < 38 years is due to both oocyte loss and accelerated follicular growth; in women > 38 years it is solely due to faster initiation of growth 16th WCM 6/4/18 25 Pre-Congress Workshop

STRAW + 10 Staging System for Reproductive Aging ST Harlow SD et al. J Clin Endocrinol Metab 2012:97:1159-68 16th WCM 6/4/18 26 Pre-Congress Workshop

Wh What I want to talk about • Endocrine changes 16th WCM 6/4/18 27 Pre-Congress Workshop

Da Daily hormone levels in women in mid-re reproductive age and older re reproductive age 22 women (either mid- reproductive age or older reproductive age) underwent daily pelvic ultrasound and blood sampling Santoro N et al. J Clin Endocrinol Metab 2003;88:5502-9 16th WCM 6/4/18 28 Pre-Congress Workshop

Age and menstrual cy cycl cle length Treloar et al. Int J Fertil 1967;12:77-126 16th WCM 6/4/18 29 Pre-Congress Workshop

Tr Trajectory of E 2 2 ch changes ( (SWAN) Tepper PG et al. J Clin Endocrinol Metab 2012;97:2872-80 16th WCM 6/4/18 30 Pre-Congress Workshop

Tr Trajectory of E 2 2 ch changes ( (SWAN) Tepper PG et al. J Clin Endocrinol Metab 2012;97:2872-80 16th WCM 6/4/18 31 Pre-Congress Workshop

FS FSH, In Inhib ibin in-B, B, AMH levels 77 women aged 21-35 or 45-55 submitted three blood samples weekly over one menstrual cycle Hale GE et al. J Clin Endocrinol Metab 2007;92:3060-7 16th WCM 6/4/18 32 Pre-Congress Workshop

DH DHEA-S S levels s (SWAN) Crawford S et al . J Clin Endocrinol Metab 2009;94:2945-51 16th WCM 6/4/18 33 Pre-Congress Workshop

Te Testosterone levels (MWMH) Burger HG et al. Menopause 2008;15:603-12 16th WCM 6/4/18 34 Pre-Congress Workshop

Wh What I want to talk about • Endocrine changes • Neurological changes 16th WCM 6/4/18 35 Pre-Congress Workshop

Ch Changes i in n neurological f function a associated wi with m menopause • Change in cognitive function • Mood change (chiefly depression) • Sleep disturbance • Vasomotor symptoms 16th WCM 6/4/18 36 Pre-Congress Workshop

De Death th from m ne neur urological or me mental di disease in n wome men n with th su surgical menopause se < < 45 Hazard ratio 5.24 95% CI 2.02-13.6 P <0.001 Rivera CM et al. Neuroepidemiol 2009;33:32-40 16th WCM 6/4/18 37 Pre-Congress Workshop

Mech Mechanism sms s of es estrogen en ne neur uropr protectio tion Scott E et al. Front Neuroendocrinol 2012;33:85-104 16th WCM 6/4/18 38 Pre-Congress Workshop

Ch Change i in c cognitive f function a across m menopausal t transition 117 mid-life women assessed according to reproductive stage Weber MT et al. Menopause 2013;20:511-17 16th WCM 6/4/18 39 Pre-Congress Workshop

Change in verbal memory y across menopause 403 women monitored over 14 years Delayed verbal memory Immediate verbal memory Epperson CN et al. J Clin Endocrinol Metab 2013;98:3829-38 16th WCM 6/4/18 40 Pre-Congress Workshop

Cogn Cognitive a agi ging i g in m mid-lif life women n (SWAN) N) 2124 participants, average age 54, followed for a median 6.5 years • Cognitive speed declined by a mean of 4.9% over 10 years • Verbal episodic memory (delayed testing) declined by a mean of 2% in 10 years • Working memory and verbal episodic memory (immediate testing) did not decline significantly • Possible interventions to slow cognitive aging in these domains were not identified in this study 16th WCM 6/4/18 41 Pre-Congress Workshop

De Depressive symptoms in perimenopause vs pr premeno nopaus pause and and po postmeno nopaus pause: : a meta-analy analysis is De Kruif M et al. J Affect Disord 2016;206:174-80 16th WCM 6/4/18 42 Pre-Congress Workshop

Pr Prevalence of sleep difficulty across the the me menopausal tr trans nsiti tion n (S (SWAN) AN) Kravitz HM, Joffe H. Obstet Gynecol Clin North Am 2011;38:567-86 16th WCM 6/4/18 43 Pre-Congress Workshop

Ne Neurological symptoms in th the menopausal tr transiti tion Brinton RD et al. Nat Rev Endocrinol 2015;11:393-405 16th WCM 6/4/18 44 Pre-Congress Workshop

Va Vasomotor symptoms and LH levels Casper & Yen. J Clin Endocrinol Metab 1981:53:1056-8 16th WCM 6/4/18 45 Pre-Congress Workshop

Ne Neuroki kinin B m-RN RNA e expressi ssing n g neurons be before e and and after er oopho phorect ectomy y Rance NE et al. Front Neuroendocrinol 2013;34:211-27 16th WCM 6/4/18 46 Pre-Congress Workshop

Po Postmenopausal changes in neuronal activity Rance NE et al. Front Neuroendocrinol 2013;34:211-27 16th WCM 6/4/18 47 Pre-Congress Workshop

KN KNDy ne neur urons, ns, GnRH nRH ne neur urons, ns, and nd the the he heat-de defenc nce mec mechan anis ism heat defence effectors Vasodilatation Rance NE et al. Front Neuroendocrinol 2013;34:211-27 16th WCM 6/4/18 48 Pre-Congress Workshop

Total duration of vasomotor sym ymptoms (SWAN) Avis NE et al. JAMA Intern Med 2015;1754:531-9 16th WCM 6/4/18 49 Pre-Congress Workshop

Wh What I want to talk about • Endocrine changes • Neurological changes • Bone and joint changes 16th WCM 6/4/18 50 Pre-Congress Workshop

Ve Vertebral osteoporosis 16th WCM 6/4/18 51 Pre-Congress Workshop

Os Osteo eocl clastogen enesi esis and and the the RANK NK/RANK NKL L in interac actio tion 16th WCM 6/4/18 52 Pre-Congress Workshop

Ch Change i in b bone re resorption (S (SWAN) NTx = urinary type 1 collagen N-telopeptide Sowers MR et al. J Clin Endocrinol Metab 2013;98:2854-63 16th WCM 6/4/18 53 Pre-Congress Workshop

Bo Bone lo loss rates es for women en 100 Forearm (BMD at age 30=100%) Spine (%) Hip and heel 90 Relative BMD 80 70 60 30 40 50 60 70 80 90 Age (years) Faulkner KG. J Clin Densitom 1998;1:279-85 16th WCM 6/4/18 54 Pre-Congress Workshop

Risk fact ctors for osteoporosis Risk for low bone mass Risk for fracture Advanced age Existing fracture Female sex Reduced BMD White or Asian race Positive family history of Thin body build osteoporotic fracture (body weight <57 kg) Advanced age Early menopause Smoking Estrogen deficiency Propensity to falls Positive family history Postural instability Chronic use of corticosteroids Lifestyle: inadequate calcium intake, cigarette smoking, excess alcohol intake, or lack Osteoporosis Society of Canada. Osteoporosis Update 1999 of physical activity 16th WCM 6/4/18 55 Pre-Congress Workshop

Es Estrogen e effects o s on a articular t tissu ssues Roman-Blas JA et al. Arthritis Res Ther 2009;11:241-55 16th WCM 6/4/18 56 Pre-Congress Workshop

Pr Prevalence of osteoarthritis by age Van Saase JLCM et al. Ann Rheum Dis 1989;48:271-80 16th WCM 6/4/18 57 Pre-Congress Workshop