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MAT and Menopause

MAT and Menopause. Lulu Zhao, MD, FACOG January 2019 Project ECHO. Objectives:. Review the role of ovarian hormones in distressing somatic and psychological symptoms Explore why the menopausal transition may be especially difficult for women in recovery

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MAT and Menopause

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  1. MAT and Menopause • Lulu Zhao, MD, FACOG • January 2019 • Project ECHO

  2. Objectives: • Review the role of ovarian hormones in distressing somatic and psychological symptoms • Explore why the menopausal transition may be especially difficult for women in recovery • Discuss ways to assist mid-life women in recovery

  3. During attempts to quit drug use, women exhibit greater unpleasant symptoms than men (Hogle and Curtin 2006, Becker and Koob 2016) • The subjective effects of cocaine and amphetamine are more intense during the follicular phase (Justice and de Wit 1999, Evans et al 2002) • Women tend to drink more alcohol during the follicular phase (Becker and Koob 2016) • In oophorectomized rats, exogenous administration of estradiol induces the rat to take more cocaine and work harder to get cocaine (Becker and Hu 2008, Roberts et al 1989)

  4. Non-reproductive functions of sex hormones Vincent and Tracey, 2008

  5. Female Sex Steroids and Pain • Estrogendecreases inhibition of u-opioid agonists in response to noxious somatic stimuli (Ratka et al 1991, Dawson et all 1996) • The emotional component of the pain experience (as opposed to the physical sensitivity) may be different between follicular and luteal phases (de Leeuw et al 2006, Choi et al 2006) • Clinical pain conditions are often known to decrease during pregnancy, when cyclic fluctuations in hormones cease and estrogen and progesterone both steadily rise (Vincent and Tracey, 2008)

  6. Female Sex Hormones and Sleep • Increases in sleep complaints coincide with periods involving large fluctuations of ovarian hormones (Mong and Cusmano 2016) • When ovarian hormones decline, sleep tends to poorer, with more night time awakenings and arousal during sleep (Lord et al 2014, de Zambotti et al 2015) • High FSH is related to waking after sleep onset, number of awakenings, and sleep arousals (de Zambotti et al 2015) • 40-60% of perimenopausal women report disturbances in sleep and insomnia (Baker et al 2015)

  7. Female Sex Hormones and Cognition • Higher estrogen predicts poorer response inhibition (Colzato et al 2010) • Lower estrogen may predispose women to prefer smaller more immediate rewards over delayed larger rewards (Smith et al 0214) • Estrogenseems to be beneficial for functioning of the prefrontal cortex, which is intimately tied to executive functioning (planning, delayed gratification, decision-making, self control). Estrogen is also an important modulator of dopamine, serotonin, glutamine, acetylcholine, and GABA. (Frick et al 2015, Jacobs et al 2011)

  8. Female Sex Hormones and Mood • Estrogen receptors are abundant in the amygdala, hippocampus, and hypothalamus, all of which play central roles in regulating mood and affect (Wharton et al 2012) • Estrogen upregulates serotonin, acetylcholine, dopamine, epinephrine, norepinephrine (Osterlund et al 2000) • In rats, injecting estradiol directly into the amygdala decreases depressive symptoms (Frye et al 2004) • Postmenopauasl women using HRT have higher hippocampal volumes than non-users and men (Eberling et al 2003, Lord et al 2008)

  9. Perimenopause can last from 4 to 12 years • Cardinal symptoms of the menopausal transition include • Hot flashes • Insomnia • Mood swings • Fatigue • Worse PMS • Vaginal dryness

  10. 96% reported one or more symptoms with a mean of 6.2 symptoms out of 14 symptoms • Over 50% reported hot flashes, night sweats, sleep disturbances, joint pains, and fatigue • Even more reported irritability and depression - the two most common symptoms in this sample • Remarkable similarity of many symptoms associated with menopause and opiate withdrawal

  11. Other Potential Interplays • Chronic use of sustained-action opioids resulted in hypogonadotrophic hypogonadism with FSH levels 30% lower in premenopausal women and 70% lower in postmenopausal women on these medications compared to non-users (Daniell 2008) • Women with earlier onset menopausal symptoms usually experience a longer duration of menopausal symptoms (Avis 2015)

  12. Adverse childhood experiences (ACE) may be a risk factor for executive complaints during the menopausal transition via reduced network connectivity • Estradiol supports the normal development and maintenance of serotonergic function, dendritic morphology, and neuronal myelination • Study found that high ACE women in menopause did worse in executive functioning Shanmugan et al. Psychoneuroendocrinology. 2017.

  13. Contra-indications to HRT • VTE • Thrombophilia • Untreated HTN • History of breast or endometrial cancer (estrogen dependent tumor) • History of coronary heart disease, stroke, or TIA • Severe active liver disease • Porphyria • Unexplained vaginal bleeding • Hypertriglyceridemia (transdermal ok) • Thyroid disease (may need adjustments after HRT)

  14. Start small. Think big. Act now. Lulu.Zhao@uhhospitals.org

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