Menopause and Osteoporosis Flashcards
Absolute contrainidcations to hormone therapy
Breast or endometrial cancer
CV disease
Active liver disease
Undiagnosed vaginal bleeding
Genitourinary syndrome of menopause (GSM)
Common symptom of menopause -
Genital symptoms: dryness, burning, irritation
Urinary symptoms: dysuria, urgency, recurrent UTI
Sexual symptoms: pain, dryness
Loss of estrogen leads to pruritis and pain
Vasomotor symptoms
Hot flashes - most common reason for HT due to impact to quality of life
Increased skin temperature, nausea, dizziness, headache, palpitations, sweats
Usually occurs within 12-24 months after last period
Recommend HT for these postmenopausal women
<60 y/o
Menopause onset within 10 years
Low risk of breast cancer and CV disease
Avoid HT for these postmenopausal women
High risk of breast cancer or CV disease
Age >60
Menopause onset >10 years ago
HT for postmenopausal women with high risk of VTE
Non-oral route
Lowest possible dose
HT for postmenopausal women with high risk of CVD
Known MI
CVD
PAD
Abdominal aortic aneurysm
DM
CKD
ASCVD >10%
Nonhormonal therapy
HT for postmenopausal with moderate risk of CVD
Transdermal estradiol with progestogen
Benefits of estrogen
Relieves genitourinary atrophy
Relieves vasomotor instability (improves sleep)
Reduces hip fractures & vertebral fractures
Reduces rate of bone resorption (does not reverse bone loss)
Risks of estrogen
AE: bloating, HA, breast tenderness
Endometrial cancer
Breast cancer
CHD
Gallbladder effects (gallstones, cholecystitis, cholecystectomy)
Endometrial cancer & estrogen
Increased risk if UNOPPOSED estrogen in women with intact uterus
Avoid if history of endometrial cancer
a progestogen is recommended in all people with an intact uterus using estrogen
Breast cancer & estrogen
Uncertain risk but avoid in women with history of breast cancer
Risk increases with use of progestogen .
Risk is related to length of use (>5 yr)
Benefits of progestogen
Decrease risk of estrogen-induced irregular bleeding
Decrease risk of endometrial hyperplasia and carcinoma
Risks of progestogen
AE: bloating, weight gain, irritability, depression
Unpredictable endometrial bleeding w/ continuous estrogen-progestin during first 8-12 months
Is Conjugated estrogen + medroxyprogesterone acetate appropriate for secondary CHD prevention?
No - not indicated for secondary prevention
Long-term use may be associated with decreased MI/ CHD death but increased risk of VTE and gallbladder disease
HT and stroke
EPT & ET have increased risk of stoke
50-59 y/o, EPT group had no significant increase in stroke
50-59 y/o ET group had double risk of stroke
HT therapy duration for postmenopausal women
-Lowest dose for least amount of time
-Reassess in 3 months to 1 year.
-D/C if asymptomatic.
-Treat for additional 3 months if symptoms recur.
-Limit to < 5 years
Menostar patch
Lowest-dose patch available
Indicated ONLY for prevention of postmenopausal osteoporosis
Benefit of SERM
Endometrial protection, so no need for progestogen
SERMs for postmenopausal patients
Ospemifene (Osphena) - indicated for vaginal dryness or severe dyspareunia
Duavee: mod-severe vasomotor symptoms & prevention of osteoporosis
Similar ADE, contraindications as estrogen
Alternatives to HT
Vasomotor symptoms:
Fezolinetant (veozah) - neurokinin 3 receptor antagonist
SSRI/SNRI paroxetine 7.5mg (briselle) is only SSRi with indication for vasomotor symptoms
No FDA approval:
soy isoflavones, evening primrose oil, black cohosh (liver tox)
Clonidine, gabapentin/pregabalin, acupuncture, hypnosis, lifestyle changes
Low bone mass definition (osteopenia)
T score between -1 and -2.5
Osteoporosis
T score < -2.5
Severe/established osteoporosis
T score < -2.5 + fragility fracture
Osteoporosis in postmenopausal women diagnosis
T score <-2.5 OR
Low-trauma spine or hip fracture, regardless of BMD
OR
Osteopenia + fragility fracture (proximal humerus, pelvis, distal forearm)
OR
Osteopenia + high FRAX fracture probability
Calcium & vitamin D recs
At least 1000mg calcium/day
Avoid doses >2500mg/day (increased risk of constipation, kidney stones, inhibited absorption zinc, iron)
Vitamin D 800-1000 units
(<70 y/o = 600 units; >=70 y/o = 800 units)
Goal level = 30 ng/mL
Gold standard for BMD
Dual-energy x-ray absorptiometry (DXA)
Measures hip, lumbar spine BMD
Drugs that can cause osteoporosis/fractures
Antineoplastics
Anticonvulsants
Glucocorticoids
GnRH agonists
Heparin
Levothyroxine (excessive)
Lithium
PPIs
SGLT2i
SSRI
FRAX
Fracture Risk Assessment Tool
Estimates fracture risk
Useful if pt has osteopenia, to determine need for pharmacologic treatment
Not validated for pts on drug therapy for osteoporosis
When to initiate drug therapy for osteoporosis
- Hip or spine fracture
- T score <-2.5 at spine, hip, or femoral neck
- T score -1 to -2.5 at femoral neck or spine AND FRAX 10 year probability is >=3% OR FRAX probabiltiy >=20%
Length of osteoporosis drug therapy
Reassess at 5 years (PO), 3 years (IV)
High risk of fracture: continue max of 10 years (PO) or 6 years (IV)
If fracture risk decreased, then drug holiday for 2-3 years
Bisphosphonate General ADRs
GI irritation (do not lay for 30 min)
Decrease in serum Ca, Phos in first month
Osteonecrosis of jaw (if high dose IV prolonged therapy - usually in patients with cancer)
A fib possible but not sure.
Bisphosphonate shown to decrease mortality
Zoledronic acid
Decreases mortality in high risk patients w/ hip fracture
Bisphosphonates
First line therapy for osteoporosis
Alendronate
Risedronate
Ibrandronate (second line therapy) (women only)
Zoledronic acid
Renal adjustment for bisphosphonates
Not recommended:
CrCl <35: alendronate, zoledronic acid
CrCl <30: risedronate, ibandronate
IV bisphosphonate options
Ibandronate (PO & IV)
Zoledronic acid (IV only)
Denosumab (Prolia)
Inhibits activation of RANKL - cytokine essential for formation, function, survival of osteoclasts
Preferred alternative to first line therapy
-Intolerant to bisphosphonates
-Poor renal function
First line if patient has very high risk or previous fractures
Must take calcium, vitamin D as it can cause hypocalcemia
Raloxifene (Evista)
SERM
Prevention & treatment of osteoporosis in postmenopausal women PLUS
risk reduction for invasive breast cancer
Decreases resorption in bone
Decreases overall bone turnover
Risk of VTE- avoid if pt history. Highest risk first 4 months.
Interacts with warfarin, levothyroxine (separate by 12 hours)
Conjugated estrogens & bazedoxifene (Duavee)
SERM + estrogen
HT. Indicated for prevention of osteoporosis - mainly in patients with persistent menopausal symptoms who cannot tolerate other drugs
CI: VTE, hepatic impairment, similar to estrogen
Parathyroid hormone related peptide analogs
Teriparatide (Forteo) & Abaloparatide (Tymlos)
Both SC daily
Indicated for treatment of osteoporosis in postmenopausal women
Forteo can also be used in men
Recommended first line therapy if very high risk or prior fractures (use x2 yrs)
Do not use longer than 2 years (possible osteosarcoma)
Increases risk of digoxin toxicity
Romosozumab (evenity)
Sclerostin inhibitor, builds bone, decreases bone resorption
SC monthly x12 months
Recommended first line therapy if very high risk or prior fractures
Do not use if MI or stroke in past year
No renal adjustments, but may be at higher risk for hypocalcemia
Calcitonin-salmon (miacalcin)
Nasal spray. Inhibits bone resorption
Typically not recommended b/c weak effect on BMD but can be used short-term for bone pain
Higher chance for malignancies
