menopause Flashcards
(31 cards)
A 50 year old gravida 4, para 3013 whose last menstrual period was twelve weeks ago complains of insomnia and hot flashes x 3-4 months.
She also states that vaginal penetration has become painful for the past four months. She asks you to “check her hormones”.
On exam, you note the lower genital tract tissues are pale and thin. Vaginal rugae are largely absent and the vaginal introitus and vault are narrow.
DO NOT MEMORIZE ANY TABLES IN THIS LECTURE
menopause
-51-52yo
-no menses x 12mo due to ovarian failure
-Perimenopause- last about 4 years
-perimenopausal + 2mo w/o menses -> menopause will occur w/i 1-2yrs
-declining estradiol -> elevated FSH and ovulatory failure due to loss of ovarian reserve
-lack of ovulation -> absence of progesterone production -> amenorrhea
dx of menpause
-clinical dx
-clinically if >40yo + no 12mo due to ovarian failure
-If hysterectomy -> get FSH level -> >30
-<40yo, consider obtaining 2-3 values on cycle day 3
diff dx of menopause
-Secondary amenorrhea may be due to:
-Pregnancy
-Medications
-Premature ovarian insufficiency
-Anorexia
-Thyroid disease
-Cervical stenosis
vasomotor sx
-hot flashes
-Experienced by almost all patients
-head -> face, neck and chest
-Catecholamine surge
-May be disabling
-87% of patients report having daily hot flashes
-33% report more than 10 hot flashes daily
-can exceed 10yrs
-Increased incidence- smokers, anxiety and/or depression
-Though obese and Black patients tend to have mild events in menopause, they also are at risk of having them more frequently and for longer
-A study of veterans found that Black patients were less likely to have menopausal symptoms documented and treated compared to white patients
etiology of vasomotor symptoms
-not well understood
-Probably involves:
-Endogenous estrogens
-Follicle-stimulating hormone
-Hypothalamic and other thermoregulatory mechanisms
-Ethnic and racial variations
-Physiologic differences
-High soy diets in Asian patients may decrease incidence
-Obesity:
-Has been implicated as a risk factor, perhaps due to insulation from adipose tissue
-Shorter duration of moderate to severe symptoms in obese Caucasians
association between vasomotor sx and risk of ds
-may be associated with cardiovascular disease and risk of cognitive illness
-One study of 226 patients (average age=59 years) not on hormone therapy demonstrated greater whole brain white matter hyperintensity volume in patients with vasomotor symptoms, especially those occurring during sleep
vulvovaginal atrophy
-40% of postmenopausal pts
-Caused by estrogen deficiency
-tissues become thinner
-Vaginal rugae are lost
-Decrease in vaginal lubrication and secretions
-dyspareunia, sexual dysfunction, vaginal dryness and pruritus
-vaginal laceration when intercourse is attempted
other effects of menopause
-Increased risk of osteopenia and osteoporosis
-Occurs in part due to lack of estrogen
-decreased bone formation and increased bone loss
-painless or devastating fx
-21% mortality within 1st year following hip fx in osteoporotic women >65 yo
-50% of women will suffer an osteoporotic fx in their lifetimes
-Menopausal hormone therapy (MHT) reduces risk of osteoporotic fx by 50%
-Benefit only persists while MHT is used
menopausal hormone therapy
unopposed estradiol -> increased risk of endometrial hyperplasia
-Both medroxyprogesterone acetate and micronized progesterone -> reduce risk of endometrial hyperplasia or carcinoma
-Dydrogesterone and micronized progesterone -> reduce risk of venous thrombotic embolism and breast cancer
-IF YOU GIVE ESTROGEN GIVE PROGESTERONE - estrogen alone causes hyperplasia
the womens health initiative (WHI)
-Double blinded, randomized, controlled study to determine the effect of estrogens on cardiac disease, osteoporosis, and cancers
-27,347 patients between the ages of 50-79 years -> Average age=63
-16,608 with uteri were randomized to receive either conjugated equine estrogens (CEE) 0.625 mg and medroxyprogesterone acetate 2.5 mg daily, or placebo
-10,73 without uteri were randomized to receive either CEE 0.625 mg daily, or placebo
-increases coronary heart ds and invasive breast carcinoma
-41% increased stroke
-29% -coronary heart ds
-Lack of protection against coronary heart disease
-Decreased risks of colorectal carcinoma and osteoporosis
-The termination of the WHI in 2002 was met with intense media coverage
-Many patients panicked that they had been exposed to danger by taking estrogens
-Many gynecologists were also concerned that they had done harm, and stopped prescribing MHT
-Potential factors:
-Type of progestogen used -> Only medroxyprogesterone was used -> Known to have vasoconstrictive effect on cardiac vessels
-Age of participants- Average age of 63 years (10 years past their last menstrual period)
-Wyeth-Ayerst provided the hormone replacement agents and placebos used in the WHI
-Conjugated equine estrogens (Premarin)
-Consists of 14 different estrogens
-Medroxyprogesterone acetate (Provera)
-Medroxyprogesterone acetate has vasoconstrictive properties
evidence refuting the initial findings of the WHI
-A study of 1000 healthy Danish patients following the WHI found that when MHT was administered estrogen and progestin (or only estrogen if status post hysterectomy)
-These patients were recently postmenopausal and between 45-58 years old
-On average, they were 50 years old and had been postmenopausal for 7 months
-Endpoints were death, admission for heart failure, and MI
-Patients had a decreased risk of death, heart failure, or MI
-No increase was noted in cancer, CVA, or VTE
WHI and the timing hypothesis
-WHI- increases coronary heart ds and invasive breast carcinoma
-decrease colon ca and osteoporosis
-decrease death from all causes if:
-<60yo, or
-<10 years postmenopausal
diseases for which there is evidence of increased risk with use of MHT
->60yrs with some comorbidity on both estrogen and progestogen:
-breast carcinoma (after 5 years)
-CVA (after 3 yrs)
-VTE (after 1-2yrs)
->60yrs with some comorbidity on estrogen only:
-gallbladder ds (after 7 yrs)
-CVA (after 7 yrs)
-VTE (after 1-2yrs)
-50-59yo healthy on both estrogen and progestin:
-VTE
->65yo -> increased risk of dementia
-The WHI Memory Study (WHIMS)- increased in conjugated equine estrogens and medroxyprogesterone acetate
entities for which there is evidence of no increased risk with use of MHT
-50-59yo using either conjugated equine estrogens with or w/o medroxyprogesterone acetate:
-Cancer mortality
-Cardiovascular mortality
-All causes of mortality
management of vasomotor sx
-hormone therapy is most effective tx!
-estrogens or estrogens with progesterone
-75% reduction of frequency and reduction in severity
-Systemic progesterone !must be included! when using systemic estrogen therapy in pts who still have uteri, unless bazedoxifene is used
FDA approved indications for use of hormone therapy
-Relief of vasomotor symptoms
-Prevention of postmenopausal osteoporosis
-Hypoestrogenism due to medical or surgical hypogonadism
-Vulvovaginal atrophy
absolute contraindications to menopausal hormone therapy
-breast or endometrial carcinoma
-suspected or known pregnancy
-undiagnosed vaginal bleeding
-prior coronary heart ds
-active liver ds
-personal or family high risk of thromboembolic ds
menopausal hormone therapy: route of delivery and risk of venous thromboembolism (VTE)
-oral estrogen may increase the risk of VTE by hepatic induction of factor 7, 8c, 9, protein C, and C-reactive protein
-transdermal estrogen avoids first-pass effect and may also suppress the effect on tissue plasminogen activator antigen and plasminogen activator inhibitor activity
-A multicenter case-control study of VTE in postmenopausal patients demonstrated an odds ratio for VTE in:
-oral estrogen- odds ratio of 5.2 (95% CI, 1.5-11.6)
-transdermal estrogen- odds ratio of 0.9 (95% CI, 0.4-2.1)
-Options:
-Oral
-Transdermal
-Sprays
-Gels
-Vaginal rings- Femring for systemic menopausal sx (requires progestogen for pts with uteri)
available estrogens for systemic use
-Estradiol (the most inexpensive option) 0.5 or 1 mg PO daily
-Conjugated estrogens 0.3 or 0.625 mg PO daily
-Transdermal estradiol patch 0.025-0.1 mg delivered daily
-Estradiol transdermal gel 0.0125 mg daily
-Estradiol topical emulsion 0.05 mg daily
-Estradiol transdermal spray 0.021-0.15 mcg daily
-Estradiol acetate vaginal ring 0.05-0.1 mg daily (use for up to 90 days)
available progesterone for systemic use with estrogen in pts with uteri
-Medroxyprogesterone acetate 2.5 mg daily, or 10 mg daily x 10 days (with latter method, patients will have withdrawal bleeding!)
-Norethindrone 0.1-0.5 mg daily
-Drospirenone 0.25 mg daily
common adverse effects of estrogen and progestin therapy
-bloating
-breakthrough bleeding
-breast tenderness
-fluid retention
-headaches
-nausea
-wt gain
other systemic hormone therapy regimens for management of vasomotor symptoms
non-hormonal tx options for vasomotor sx
-know the first 3 meds in the chart
-insufficient data to support the use of herbal therapies
-however, chinese herbal medicine, when used with acupuncture, has been found to be as effective as MHT
-hot flashes (data do not support):
-increasing fluid intake
-layering clothes
-lowering thermostat
-decrease consumption of alcohol and caffeine-based products
-NEW non-hormonal pharm for vasomotor sx:
-Neurokinin B receptor antagonists that work directly on the hypothalamus
-Fezolinetant 45 mg daily -> Avoid with history of cirrhosis and/or renal disease
-Elinzanetant (FDA approval pending)
