menopause Flashcards
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
-physiologic ovarian failure that generally occurs around 51-52yo -> cessation of menses
-Menopause- no menses x 12 months due to ovarian failure
-Perimenopause- last about 4 years
-By the time a perimenopausal pt has gone 2 months without menses -> likely menopause will occur within 1-2yrs
-declining estradiol levels cause elevated FSH and ovulatory failure due to loss of ovarian reserve
-lack of ovulation causes absence of progesterone production
-absence of progesterone results in amenorrhea
evidence of decreased ovarian reserve (dont need to know)
-Transforming growth factor-β (TGF- β) is a group of polypeptides that are involved in some regulation of embryologic and adult homeostatic mechanisms
-Those involved in ovarian function include anti-Müllerian hormone (AMH) and inhibin-B
-AMH can be identified clinically and can help predict the likelihood of failure regarding assisted reproductive technology
dx of menpause
-clinical diagnosis
-May be made clinically in patients over age 40 who have had no menses for 12 months due to ovarian failure
-In patients s/p hysterectomy, obtain follicle-stimulating hormone (FSH)
-FSH at or above 30 mIU/ml in menopause
-For patients <40 yo, consider obtaining 2 or 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
-A sensation of extreme heat, usually starting at the head and extending into the face, neck and chest
-May be described as “being thrust in an oven”
-May be accompanied by sweating, flashing, palpitations
-Catecholamine surge may occur with vasomotor symptoms
-May be disabling
-87% of patients report having daily hot flashes
-33% report more than 10 hot flashes daily
-Duration varies, but can exceed 10 years
-Increased incidence noted in patients who are smokers or who have 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
-There is evidence that vasomotor symptoms 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
-Affects as many as 40% of postmenopausal patients
-Caused by estrogen deficiency
-Lower genital tract tissues become thinner
-Vaginal rugae are lost
-Decrease in vaginal lubrication and secretions
-Results in dyspareunia, sexual dysfunction, vaginal dryness and pruritus
-May result in vaginal laceration when intercourse is attempted
other effects of menopause
-Increased risk of osteopenia and osteoporosis
-Occurs in part due to lack of estrogen
-Results in decreased bone formation and increased bone loss
-May lead to painless or devastating fractures
-21% mortality within 1st year following hip fracture in osteoporotic women >65 yo
-50% of women will suffer an osteoporotic fracture in their lifetimes
-Menopausal hormone therapy (MHT) reduces risk of osteoporotic fracture by 50%
-Benefit only persists while MHT is used
menopausal hormone therapy
-1970s- use of unopposed estradiol -> increased risk of endometrial hyperplasia and carcinoma
-When patients with uteri used estrogens alone, the risk of endometrial hyperplasia was as high as 62% after three years of use
-Both medroxyprogesterone acetate and micronized progesterone have been found to be effective in significantly reducing the risk of endometrial hyperplasia or carcinoma based on endometrial biopsies and/or hysteroscopies
-Dydrogesterone and micronized progesterone were also found to reduce the 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
-In 2002, after 5.2 years, this study was terminated prematurely due to achievement of endpoints regarding coronary heart disease and invasive breast carcinoma
-41% increased risk of stroke
-29% of patients developed coronary heart disease
-Lack of protection against coronary heart disease
-Decreased risks of colorectal carcinoma and of osteoporosis were also demonstrated
-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
the timing hypothesis
-Meta-analyses of additional randomized, controlled trials have demonstrated a reduction in risk of death from all causes as well as reduction in coronary heart disease in patients who are:
-<60 years old, or
-<10 years postmenopausal
diseases for which there is evidence of increased risk with use of MHT
-in pts >60yrs with some comorbidity on both estrogen and progestogen:
-breast carcinoma (after 5 years)
-cerebrovascular accidents (after 3 yrs)
-venous thromboembolism (after 1-2yrs)
-in pts >60yrs with some comorbidity on estrogen only:
-gallbladder ds (after 7 yrs)
-cerebrovascular accident (after 7 yrs)
-venous thromboembolism (after 1-2yrs)
-in relatively health pts 50-59 on both estrogen and progestin:
-venous thromboembolism
dementia and MHT
-Initiation of MHT at or beyond age 65 is associated with an increased risk of dementia
-The WHI Memory Study (WHIMS) noted 23 additional cases per 10,000 person-years in patients receiving conjugated equine estrogens and medroxyprogesterone acetate
entities for which there is evidence of no increased risk with use of MHT
-In patients aged 50-59 years old using either conjugated equine estrogens with or without medroxyprogesterone acetate:
-Cancer mortality
-Cardiovascular mortality
-All causes of mortality
management of vasomotor sx
-hormone therapy is the most effective tx for vasomotor sx due to menopause!
-such therapy consists of estrogens or estrogens with progesterone
-Produces up to 75% reduction of frequency of hot flashes as well as a reduction in severity of symptoms
-Systemic progesterone !must be included! when using systemic estrogen therapy in patients 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 the 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:
-Patients using oral estrogen had an odds ratio of 5.2 (95% CI, 1.5-11.6)
-Patients using transdermal estrogen had an odds ratio of 0.9 (95% CI, 0.4-2.1)
available routes for administration of systemic estrogens
-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
-while data do not support such changes, certain lifestyle modifications may benefit pts with hot flashes:
-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)
vaginal estrogens available for local use
-Estradiol ring 7.5 mcg/day x 90 days (be cautious which vaginal ring you prescribe!)
-Estradiol cream 0.1 mg/gm
-Start either with BIW use, or daily use x 2 weeks and then begin BIW use
-Conjugated estrogen cream 0.625 mg/gm
-Start either with BIW use, or use daily x 2 weeks and then begin BIW use
-No need to use progesterones with vaginal estrogen alone
genitourinary syndrome of menopause (GSM)
-Encompasses vaginal, urinary, and sexual symptoms due to a deficiency of estrogen in patients after the menopause and in people who have survived cancer
-Includes:
-Vulvovaginal atrophy
-Urinary incontinence
-Sexual dysfunction
-Affects 10-40% of women will be affected by vaginal atrophy
-Systemic or vaginal estrogen therapy may be used, but if the patient has no systemic symptoms, vaginal estrogen should be employed instead
-Progestogens are not required for endometrial protection with vaginal estrogen therapy
contraindication to low dose vaginal estrogen therapy
Breast, endometrial, or other estrogen-dependent cancer, unless discussed with and approved by the patient’s oncologist
hormonal tx options for initial management of menopausal lower genital tract sx
hormonal tx of menopausal lower genital tract sx
-systemic absorption and risk of endometrial carcinoma
-no need to use progesterones to prevent endometrial carcinoma in pts using vaginal estrogen therapy alone
-when treating pt with hx of estrogen-sensitive breast cancer with menopausal lower genital tract sx -> consider using non-hormonal methods first
-consider consultation with the pts oncologist before using vaginal estrogens
compounded bioidentical hormone therapy
-After the WHI, many patients were reluctant to begin hormone replacement therapy obtained through their medical practitioners
-Some patients turned to compounding pharmacies advertised on the Internet that promised individualized hormone therapy formulated based on a salivary hormone test
-These preparations are usually not covered by insurance plans and do not offer the safety data or efficacy provided by the Food and Drug Administration
-Compounded agents are not subject to testing for:
-contents
-purity
-quality
-safety
-efficacy
-different forms of estrogens and progestogens may be used
-there include estradiol-17, estrone, and progesterone
-these may result in an increased risk of:
-endometrial hyperplasia
-venous thromboembolism
-osteopenia and osteoporosis
ACOG committee opinion on compounded bioidentical menopausal hormone therapy
-“Evidence is lacking to support superiority claims of compounded bioidentical hormones over conventional menopausal hormone therapy.
-“Conventional hormone therapy is preferred over compounded hormone therapy given the available data.
-“There is no evidence that hormonal levels in saliva are biologically meaningful…salivary testing does not currently offer an accurate or precise method of hormone testing.”
MHT and tx and bone loss
-No RCTs have demonstrated a reduced incidence of fractures in patients with osteoporosis on MHT
-However, MHT (estrogens with progestogens or bazedoxifene) does have a beneficial effect in preventing osteoporosis
duration of menopausal hormone therapy
-one can try to taper or simply stop hormone therapy
-discontinuation should be individualized
-some pts may need to continue MHT until after age 65
