menopause and mood - jean hailes€¦ · menopause and mood women’s health across the lifespan gp...
TRANSCRIPT
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Menopause and Mood
Women’s health across the lifespan GP symposium, Epworth, June 4 2016
Dr Roisin Worsley, FRACPEndocrinologist,
Jean Hailes at Epworth Freemasons & Alfred Hospital
Menopause
• The final menstrual period
• Perimenopause – the time around the final menstrual period
• Average age of FMP 51• Average onset of
perimenopause 47
Harlow SD, Gass M,et al.. Climacteric : 2012
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CD
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Hormones across the menopause transition
Burger et al Human Reprod Update 2007
One woman’s hormones in the months prior to menopause
‐36 months ‐25 months ‐17 months ‐7 months
Burger et al Menopause 2008
Menopausal symptoms
• 1 in 3 women have severe psychological symptoms
• 1 in 4 have severe physical symptoms
Mishra GD, Kuh D.. BMJ 2012
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Menopausal symptoms
• Vasomotor symptoms (hot flushes and night sweats)
• Vaginal dryness• Sleep disturbance• Headaches• Joint pain• Mood changes
Symptoms can last many years
• For half of women, symptoms vasomotor symptoms last 7 years
• For half of women, vasomotor symptoms persist 4.5 years after the final menstrual period
• Symptoms persist much longer in a substantial number of women
Date of download: 9/16/2015 Copyright © 2015 American Medical Association. All rights reserved.
From: Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition
JAMA Intern Med. 2015;175(4):531-539. doi:10.1001/jamainternmed.2014.8063
Kaplan-Meier Estimates of Total VMS Duration of Frequent VMS by Menopausal Transition Stage at First VMS Report (A) and by Race/Ethnicity (B)A, By menopausal transition stage at first VMS report. B, By race/ethnicity. VMS indicates vasomotor symptoms.Menopausal transition stage at first VMS report is missing for 9 participants. Median duration for each group is calculated as the value on the x-axis corresponding to the intersection of the dashed horizontal line (50%) with the group’s survival curve.
Figure Legend:
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020
4060
8010
0P
erce
nt
41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
020
4060
8010
0P
erce
nt
41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
Age in years
Mild hot flushes No hot flushes
Mild night sweats No night sweatsModerate‐severe night sweats
Moderate‐severe hot flushes
Prevalence of hot flushes and night sweats in Australian women aged 40-65 years
Gartoulla, Worsley et al, Menopause, 2015
Mood symptoms at menopause
• Women without a history of anxiety are TWICE as likely to develop anxiety in perimenopause and early postmenopause Bromberger et al Menopause 2013
• Women are TWO to FOUR times more likely to feel depressed during the menopause transition Freeman et al Arch Gen Psych 2006; Bromberger et al Obstet Gynecol Clin North Am 2011
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Vasomotor & depressive symptoms
Blumel, 2004
Hunter, 2013
Joffe, 2002
Juang, 2005
Reed, 2009
Opperman, 2012
Brown, 2009
Yen, 2009
Li, 2008
Hunter, 2013
Bosworth, 2001
Avis, 2001
Cohen, 2006
Freeman, 2006
Freeman, 2009
Bromberger, 2010
Reference
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Fig 1 Profiles of psychological symptoms across midlife and according to age relative to menopause.
Gita D Mishra, and Diana Kuh BMJ 2012;344:bmj.e402
©2012 by British Medical Journal Publishing Group
Depressive symptom scores by menopausal status
020
4060
8010
0
Perc
ent
Premenopausal Perimenopausal Post ≤55 y Post >55 yMenopause status
Moderate-severe depressionBDI ≥ 20
Mild depression BDI 14-19
Mean anxiety scores by menopausal status (lower score = more anxious)
17.216.1 15.7
17.6
0
5
10
15
20
25
Premenopausal Perimenopausal Postmenopausal ≤ 55 y Postmenopausal > 55y
Mean An
xiety Score
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Depressive and anxiety symptoms
After taking into account body mass index (kg/m2), carer status, marital status, employment, housing security, history of mental illness, smoking, weekly binge drinking and education level,
Compared to premenopausal women, postmenopausal women ≤ 55:
– More likely to have depression OR 1.7 (95% CI, 1.1-2.7, p
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Psychotropic medication use by menopausal status
0.41.7 1.7
16.5
11.8
4.7
18.1
1.3
3.2
8.4
22.4
1 1
3.9
19.9
0
5
10
15
20
25
Moodstabiliser Antipsychotic Benzodiazepine Antidepressant
Percent
Premenopausal Perimenopausal Post ≤ 55 years Post > 55 years
Menopause and mood
• Mood symptoms improve after the menopause transition but……Freeman et al JAMA Psychiatry 2014
• This can take years• Hormone therapy may improve depression
during perimenopause Worsley, 2012
• But….• Many women are intolerant of
progestins Andreen, 2010
Hormone therapy
• Estrogen the most effective treatment for hot flushes
• Patches, tablets, gel, pessaries• Causes endometrial thickening / increased risk
of endometrial cancer so women with a uterus must also receive a progestin
• Maybe 30% women negative effects progestin (mood) Andreen, 2010
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HT- risks from WHIEstrogen + Progestin Estrogen Only
Breast Cancer ↑a er 2 yearsHR 1.24 (95% CI, 1.01‐1.53) after 5 yrs, remains elevated after stopping
↓Early post‐interventionHR, 0.55 (95% CI, 0.34‐0.89)
Stroke HR 1.37 (1.07‐1.76) HR, 1.35 (1.07‐1.70)
DVT ↑1.87 (1.37‐2.54) ↑1.48 (1.08‐2.07)
CHD ↔ ↔
All cause mortality ↔ ↔
Monash Alfred Psychriatry Reseacrh Centre
Chlebowski et al, JAMA Oncol 2015; Mason et al JAMA 2013
Date of download: 9/29/2015 Copyright © 2015 American Medical Association. All rights reserved.
From: Menopausal Hormone Therapy and Health Outcomes During the Intervention and Extended Poststopping Phases of the Women’s Health Initiative Randomized Trials
JAMA. 2013;310(13):1353-1368. doi:10.1001/jama.2013.278040
Absolute Risks of Health Outcomes by 10-Year Age Groups in the Women’s Health Initiative Hormone Therapy Trials During the Intervention PhaseNone of the age interactions were statistically significant (at the P
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Change in case number per 1000 women per 5 years of treatment in women aged 50-59
Estrogen + Progestin Estrogen only
All cause mortality ‐5.3 ‐5.0
CHD ‐0.9 ‐3.8
Breast Cancer +6.8(NAMS +8 per 10,000)
‐1.5
Venous thromboembolism +5 +2
Stroke +1.0 +1.2
Fracture ‐4.9 ‐5.9
Cholecystitis (all ages) +9.6 +14.2
T2DM ‐11 ‐11
Colorectal cancer ‐1.2 0
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Taken from Martin et al Menopausal Hormone therapy: benefits and risks. Uptodate July 2015
Antidepressant use in perimenopausaldepression
• Commonly used to treat anxiety, depression, sleep problems, hot flushes
• SNRIs popular (low dose venlafaxine )• Issues – discontinuity problems, blunting,
aggression, problems with tachyphylaxis• Hypertension w venlafaxine• ?fracture risk
Menopause and pre-existing mental illness• Bipolar Disorder
– More depressive symptoms Marsh et al Bipolar Disord 2012– ?Hormone therapy helpful Freeman et al J Clin Psych 2002
• Schizophrenia– ?worse mood/QoL ?improvement w age Seeman, Maturitas 2012
• Depressive Disorders– Recurrence more common Payne et al, J Aff Dis 2002
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Mood and the menstrual cycle
• Many women notice changes in their illnesses/symptoms with the menstrual cycle
• Changes in mood can also occur– Premenstrual Syndrome– Premenstrual Dysphoric Disorder– Premenstrual Exacerbations of Depression/Anxiety
• PMS often worsens in the 40s as women approach menopause
The menstrual cycle
For a 28 day cycle:• Day One – first day of bleeding• Day 14 – ovulation• Follicular phase: Day 1 – Day 14• Luteal Phase: Day 15-28• Premenstrual: 5 days (or more!!) before
bleeding e.g. Day 23-28
Premenstrual syndrome
• Symptoms in the 1-2 weeks before a period that get better after a period
• Around 80% of women notice some symptoms premenstrually – normal!
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More intrusive symptoms• Physical• Emotional & behavioural
Premenstrual syndrome
Fatigue
Irritability
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Bloating
Anxiety
Cravings
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Low mood
Fatigue Irritability Bloating Anxiety/tension Breast tenderness Mood lability DepressionFood cravings Acne
Increased appetite Oversensitivity Swelling Expressed anger Crying easily Feeling of isolation Headache Forgetfulness Gastrointestinal symptoms Poor concentration Hot flashes Heart palpitations Dizziness
Common symptoms of PMS
Mortola, JF, Girton, L, Beck, L, Yen, SS, Diagnosis of premenstrual syndrome by a simple prospective reliable instrument. Obstet Gynecol 1990; 76:302. Reprinted with permission from the American College of Obstetricians and Gynecologists (Obstetrics and Gynecology, 1990; 76:302). FROM UPTODATE
Premenstrual dysphoric disorder
• PMDD diagnosis focuses on mood
• 5-10% women reproductive age
C. Guille et al. / Epilepsy & Behavior 13 (2008) 12–24
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PMDD diagnosis
Five of : • depression, irritability, anxiety, affect
lability• decreased interest, difficulty concentrating,
fatigue, feeling out of control, insomnia, change in appetite, breast tenderness, breast swelling
• interfere with usual activities
PMDD Diagnosis: CYCLICITY
• Symptoms occur in the luteal phase, remit in the first few days of cycle.
• Symptom free in follicular phase.
• Diagnosis requires a 2 month daily DIARY
C. Guille et al. / Epilepsy & Behavior 13 (2008) 12–24
Tests
• No diagnostic testsLook for:• Other illnesses – thyroid• Menopause transition• Other mood disorder• Current medications
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? cause
• Hormonal fluctuations in the menstrual cycle
• Normal hormone levels / Different brain response
• Progesterone metabolite Allopregnanolone
• ↑Inflammatory markers in luteal phase (IL‐4, IL‐10, IFN‐Ύ; affective symptoms correlate w IL‐2, physical symptoms w IL‐4)
Neuropsychopharmacology (2006) 31, 1249–1263. doi:10.1038/sj.npp.1300952; published online 23 November 2005
Physiological ALLO concentrations
100nM/L
5nM/L
pregnancy
menstrual cycle
(0-40 weeks)
Compiled from: Maguire,Psychoneuroendocrinology (2009) 34S, S84—S90 ; Luisi, S. et al. J Clin Endocrinol Metab 2000;85:2429‐2433; Genazzani, A. R. et al. J Clin Endocrinol Metab 1998;83:2099‐2103
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ALLOPREGNANOLONE CONCENTRATION
low luteal high
ALLO in PMDD ? A paradoxical response
Andreen et al, Sex steroid induced negative mood may be explained by the paradoxical effect mediated by GABAa modulators. Psychoneuroendocrinology (2009)
IRRITABILITY SCORE
low
high
Neuropsychopharmacology advance online publication 09 September 2015.doi:10.1038/npp.2015.246
Figure 3
Improvement in symptoms by avoiding luteal rise in allopregnanolone by blocking 5 alpha reductase
Neuropsychopharmacology
Treatment - lifestyle
• Diet ?low salt ?low GI ?more carbs• Maintain weight• Sensible alcohol use• Exercise – throughout cycle• Avoid smoking• Stress reduction• Planning
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Treatment - over the counter
• ?calcium• ?Vitex agnus castus (Chasteberry)• ?Other herbs: St John’s Wort
Treatment - medication
• Oral contraceptive pill use continuously (take sugar pills every three months)
• Antidepressants (SSRIs) help brain to better respond to hormonal fluctuations
• Other
The oral contraceptive pill
• Estrogen + progestin• High discontinuation rate due to mood side
effects• Progestins cause worse mood in some
women
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Progestin in the OCP & anxiety disorders
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11.6 11.8
21.4
35.5
Levonorgestrel Cyproterone Other Drospirenone
Percent
Anxiety disorder
Depression scores by oestrogen dose
0
1
2
3
4
5
6
7
20mcg 30mcg 35mcg+
Med
ian Be
ck Dep
ression Inventory Score
Ethinyl Estradiol dose in the OCP
Choosing an OCP
• It’s difficult!• Mood SEs with OCP I like:
– Zoely– Qlaira– Valette
• & I avoid Yaz/Yasmin
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Mood symptoms at menopause
• Is it my hormones?• Usually it’s a bit of everything• Often need a combination of therapies:
– Lifestyle measures– Psychological therapies– Hormone therapy– Antidepressants