exam 3 - menopause Flashcards
(37 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
-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 (FYI only)
-Includes AMH and inhibin-B from TGF-β family
-AMH used clinically to assess ART success
dx of menopause
-Clinical dx if >40 with no menses for 12 months
-If s/p hysterectomy: check FSH (>30 mIU/mL)
-<40 yo: get FSH on cycle day 3 (x2-3)
differential dx of menopause
-Pregnancy
-Meds
-Premature ovarian insufficiency
-Anorexia
-Thyroid disease
-Cervical stenosis
vasomotor sx
what comorbidies change incidence and duration
-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 sym
etiology of vasomotor sx
-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
vasomotor sx & disease risk
-Linked to ↑ CVD risk and cognitive decline, ↑ white matter lesions (esp. night symptoms)
-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
-Due to estrogen deficiency
-Lower genital tract tissues become thinner
-Vaginal rugae are lost
-Decrease in vaginal lubrication and secretions
-Causes dryness, dyspareunia, pruritus
-↑ risk of laceration with intercourse
other menopause effects
-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 (MHT)
-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 WHI trial
-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
-RCT of estrogens (CEE ± MPA)
-Average age 63
-↑ stroke and CHD → study stopped
-Also showed ↓ colorectal CA & osteoporosis
WHI study concerns
-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
💡 Takeaway:
Timing matters. Starting MHT early in menopause may be safe and beneficial, unlike in the older WHI cohort.!!!!!!
-Participants were older (avg 63)
-MPA may cause vasoconstriction
-Media overreaction led to drop in MHT use
refuting WHI
-Danish trial: ↓ death, HF, MI in 50 yo women on MHT
-No ↑ in cancer, stroke, or VTE
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
MHT & dementia
-Starting MHT ≥65 → ↑ dementia (WHIMS study)
-23 extra cases per 10,000 person-years
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
vasomotor sx tx
-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
-Estrogen (± progesterone) is most effective
-Up to 75% ↓ in sx
-Include systemic progesterone if uterus present
FDA-approved MHT uses
-Vasomotor sx
-Osteoporosis prevention
-Hypoestrogenism
-Vulvovaginal atrophy
absolute contraindications to MHT
-Breast/endometrial CA
-Pregnancy
-Undiagnosed vaginal bleeding
-CAD
- active liver disease
- high risk of thromboembolic disease
oral vs transdermal estrogen
-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)
📈 Oral Estrogen
Increases VTE risk via hepatic first-pass effect:
Induces clotting factors: VII, VIIIc, IX
Increases Protein C resistance and C-reactive protein
Odds ratio (OR) for VTE: 5.2
(95% CI: 1.5–11.6)
📉 Transdermal Estrogen
Bypasses liver (no first-pass effect)
Less effect on coagulation factors
↓ impact on tissue plasminogen activator antigen
↓ plasminogen activator inhibitor activity
Odds ratio (OR) for VTE: 0.9
(95% CI: 0.4–2.1)
💡 Takeaway:
Transdermal estrogen is safer for VTE risk.
Consider it especially in patients with VTE history, obesity, or clotting risk.
routes of systemic estrogen
-Oral
-Transdermal
-Sprays
-Gels
-Vaginal rings- Femring for systemic menopausal sx (requires progestogen for pts with uteri)
available estrogens
-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)
-Estradiol (PO, patch, gel, spray)
-CEE
-Vaginal ring (systemic use, not local!)
