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Men's and women's health lec 2

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Amr Elkady

on 4 January 2013

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Transcript of Men's and women's health lec 2

Timeline 2013 2009 2010 2011 2012 Team 0 + - = 9 8 7 1 2 3 4 5 6 c vasomotor symptoms treatment history of cancer , specifically breast cancer

history of cardiovascular disease

quality of life with menopause symptoms occuring Osteoporosis Hormone therapy /menopause treatment of vasomotor symptoms diffenation common symptoms Genitourinary atrophy decrease in estrogen pH changes and becomes more basic loss of lubrication leads to dyspareunia Estrogen and progesterone tharapy primary indication treatment of moderate to severe menopause symptoms and osteoporosis treatment when other treatments have failed SSRIs are the best for vasomotor symptoms Venlafaxine 75 mg orally every day

fluoxetine 20mg orally very day

paroxetine 20 mg orally every day

sertraline 100 mg orally every day Soy isoflavones ...May still have adverse effects similar to conjugated estrogens Evening primrose oil ....No solid evidence for use Black cohosh ..Some effectiveness for vasomotor symptoms Bioidentical hormones ... May still have adverse effects similar to conjugated estrogens benefits of estrogen relieves genitourinary atrophy

relieves vasomotor instability

osteoporosis reduction in hip fractures by 25% reduction in vertebral fractures by 50% Note : Estrogen reduces the rate of resorption but does not restore bone loss. insomnia and fatigue improved by decreasing hot flashes

mood changes,,

sexual function may help with vaginal atrophy thus decreasing pain with sexual intercourse Risks of estrogen Endometrial cancer risk increase withs with unopposed estrogen use in women with an intact uterus .Cancer is dependant on duration of estrogen use ; cancer risk increases 8 fold for 10-20 years of estrogen use .Not recommended for use in women with a history of endometrial cancer. A progestogen is recommended in all women with an intact uterus using estrogen,, Note the progstin is recommended in all women with an intact uterus using estrogen . others used for vasomotor symptoms

clonidine ,megestrol ,gabapentin increase also breast cancer ,, cardiovascular out comes ,venous thromboembolism adverse effects : bloating ,headache , breast tenderness ,uterine bleeding , the benefits of progestogen decreased risk of estrogen induced irregular bleeding endometrial hyperplasia ,and carcinoma

protection against breast cancer

enhancement of estrogen prophylaxis of osteoporosis Conjugated estrogens, medroxyprogesterone acetate, and cardiovascular outcomes

A longer duration of use leads to a greater decrease in relative hazards in
nonfatal MI and CHD death; however, there was an increased risk of VTE and gallbladder disease.
Conclusions of study, HT was not appropriate to initiate for secondary prevention of CHD, but for
women already using HT, long-term use might benefit from a decrease in CHD. A follow-up study
suggested that HT use in older women with CHD for longer than 6.8 years had a higher risk of VTE
and biliary tract surgery Further information suggests increased risk of ovarian cancer (considered rare, data conflicting)
and lung cancer in older women with a history of smoking Hormone regimens
.......................................................
a. Unopposed estrogen
i. Conjugated estrogen taken daily without interruption is suggested for women with a
hysterectomy; women with a uterus must have a progestogen and cannot use estrogen alone
(use of estrogen alone in women with a uterus increases the risk of endometrial cancer Transdermal estradiol patches in women who are intolerant of oral preparations or who need
alternative therapy with potentially less risk of VTE Vaginal preparations for women with genitourinary atrophy. In general, topical treatment is
sufficient and should be tried before oral preparations Therapy duration—Lowest dose for least amount of time. Check after 3 months to 1 year and
attempt to discontinue if asymptomatic; if symptoms recur, treat for an additional 3 months;
best to limit treatment to less than 5 years Estrogen plus cyclic progestogen
i. Continuous estrogen daily
ii. Cyclic progestogen such as medroxyprogesterone acetate 5−10 mg/day or the equivalent for
10–14 days/month
iii. Similar to female cycle with a withdrawal bleed each cycle Estrogen plus continuous progestogen
i. Continuous estrogen daily
ii. Continuous progestogen 1.5–2.5 mg/day or the equivalent without interruption
iii. Irregular menstrual cycle for the first 8–12 months of HT
d. Intermittent
i. Continuous estrogen daily
ii. Three days on progestogen, 3 days off
iii. Seldom used Monitoring criteria

a. Monthly: Breast self-examination

b. Annually: Breast examination, mammography, pelvic examination

c. Evaluation of vaginal bleeding

i. Unopposed estrogen: Any episode of vaginal bleeding unless the woman has had a normal
assessment in the past 6 months

ii. Estrogen plus cyclic progestogen: If bleeding occurs other than at the time of expected
withdrawal bleeding

iii. Estrogen plus continuous progestogen: If bleeding is heavier than normal, is prolonged
(longer than 10 days at a time), is frequent (more often than monthly), or persists for more than 10 months after beginning therapy Note


Micronized estradiol
(0.1 mg/g)
Initial: 2–4 g/day for 1–2 weeks; then 1 g/day
applied vaginally
Premarin Conjugated estrogens
(0.625 mg/g)
0.5–2 g/day applied vaginally (WHO) Definitions Based on T-scores (T-score indicates that for every standard
deviation [SD] below the mean young adult BMD, fracture risk increases 2-fold)

1. Normal = BMD within 1 SD of the young adult mean

2. Osteopenia = BMD between -1 SD and -2.5 SD below the young adult mean

3. Osteoporosis = BMD at least - 2.5 SD below the young adult mean 1. Risk factors for osteoporotic fractures
a. Female sex
b. White race
c. Poor nutrition, long-term low-calorie intake
d. Early menopause (before age 45) or prolonged premenopausal amenorrhea
e. Estrogen deficiency
f. Drugs: Glucocorticoids, heparin, anticonvulsants, excessive levothyroxine, GnRH agonists,
lithium, cancer drugs
g. Low body mass index (BMI) or low weight
h. Family history of osteoporosis
i. Low calcium and vitamin D intake
j. Sedentary lifestyle, decreased mobility
k. Cigarette smoking
l. Alcoholism
m. Dementia
n. Impaired eyesight despite adequate correction
o. Previous fractures
p. History of falls assessment

i. Dual-energy x-ray absorptiometry (DXA)
ii. Peripheral DXA
iii. FRAX score (a) Used to estimate fracture risk
(b) Most useful to estimate for patients with low BMD of hip
(c) Recommended for postmenopausal women and men age 50 or older
(d) Useful to determine whether patients with osteopenia need pharmacologic treatment
(e) Not validated for patients on drug therapy for osteoporosis Recommended BMD testing
i. All women 65 years and older (NAMS, ACOG, AACE), men older than 70 (NOF)
ii. Men aged 50–70 years with risk factors or previous fractures
iii. All postmenopausal women with medical causes of bone loss (NAMS)
iv. Postmenopausal women younger than 65 years with at least one of the following:
(a) Previous fracture after menopause other than skull, facial bone, angle, finger, and toe;
thinness (body weight less than 127 lb or BMI less than 21 kg/m2); history of hip fracture
in a parent; current smoking; rheumatoid arthritis, alcohol intake of 2 units/day or more
(1 unit = 12 oz of beer, 4 oz of wine, 1 oz of liquor) (NAMS)
(b) With any risk factor listed in section B1 (ACOG)
(c) Previous fracture not caused by severe trauma after age 40–45 (AACE)
(d) Thinness (body weight less than 127 lb), family history of spine or hip fracture (AACE)
(e) Osteopenia identified radiographically (AACE)
(f) Starting or taking long-term systemic glucocorticoids for 3 months or longer (AACE, NOF) Initiation of drug therapy (AACE, NOF, NAMS – most updated)
i. If hip or spine fracture
ii. If BMD T-score is 2.5 or below at spine, hip, or femoral neck
iii. If BMD T-score between 1.0 and 2.5 at femoral neck or spine and 10-year probability of
hip fracture greater than 3% or 10-year probability of major osteoporosis-related fracture of
greater than 20% based on the FRAX system
g. Follow up on BMD-DXA every 2 years Osteoporosis Treatments 1. Bisphosphonates
a. Alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), zoledronic acid (Reclast)
b. Inhibits normal and abnormal bone resorption
c. First-line therapy, exception: ibandronate second-line therapy
d. Efficacy—Reduces vertebral and non-vertebral fractures by 30%–50% (see individual agents)
e. Adverse events (not dose-dependent):
i. Gastrointestinal (GI): Flatulence, acid regurgitation, esophageal ulcer, dysphasia,
abdominal distention, gastritis. To reduce the risk of GI adverse effects, those taking oral
bisphosphonates should not lie down for 30–60 minutes after taking the dose.
ii. Miscellaneous: Headache, musculoskeletal pain, rash
iii. Laboratory values: Decreases in serum calcium concentrations; decreases in serum
phosphorus concentrations in the first month
iv. Osteonecrosis of jaw: Most are associated with dental procedures. Most cases occur in
patients with cancer after prolonged therapy. Intravenous administration has a greater risk
than oral therapy.
v. Atypical fractures and esophageal cancer: The U.S. Food and Drug Administration (FDA)
is monitoring these ADRs; for now, the recommendation is to continue use as directed by
physician.
f. Drug-food interactions—Wait at least 30 minutes after taking bisphosphonate before taking any
medications, food, or drinks except water, except with ibandronate—must wait 60 minutes g. Dosage for osteoporosis:
i. Alendronate: 10 mg/day or 70 mg/week; taken for 3 years. Alendronate (daily dose regimen)
was shown to decrease vertebral fractures by 47% and hip fractures by 51% (FIT study
[Fracture Intervention Trial]) in women with previous fractures.
ii. Alendronate with vitamin D: 70 mg/day with 2800 IU of vitamin D3 or 70 mg/week with
5600 IU of vitamin D3
iii. Risedronate: 5 mg/day or 35 mg/week or 150 mg once monthly, decreases non-vertebral
fracture risk by 33%–39% and vertebral fracture by 41%–49%
iv. Ibandronate: 2.5 mg/day or 150 mg once monthly orally, waiting at least 60 minutes before
eating, drinking, or taking another drug, or 3 mg intravenously every 3 months; increases
BMD at spine and hip; however, studies show only a decreased risk of vertebral fractures;
intravenous administration is also available
v. Zoledronic acid: 5 mg intravenously annually; reduces non-vertebral fracture risk by 25%,
hip fracture by 40%, and vertebral fracture risk by 70%. Lack of GI adverse effects, higher
risk of atrial fibrillation with zoledronic acid than with placebo
(1.3% vs. 0.4%); hypocalcemia may occur, patient must take calcium and vitamin D
supplements. Infusion reactions occur, requiring pretreatment with acetaminophen. FDA
warning 2011 regarding contraindicated use in patients with renal impairment or with
creatinine clearance less than 35 mL/minute shown to decrease mortality in high-risk
patients who have suffered a hip fracture (only bisphosphonate shown to decrease mortality Renal impairment
a. Recommended for all patients with osteoporosis to maintain normal

calcium concentrations and

to prevent hypocalcemia associated with other drug treatments

for osteoporosis
b. Elemental calcium intake: Avoid doses higher than 2500 mg/day. Higher

doses may increase risk
of constipation, contribute to kidney stones, and inhibit absorption of zinc or iron.
c. Most common forms: Calcium carbonate (take with food), calcium citrate (take with or without
food) 2. Calcium Vitamin D Recommended for all patients with osteoporosis; promotes calcium reabsorption
b. Minimal dose = 800 IU/day for those older than 70 years, 600 IU/day for those younger than 70
years (Institute of Medicine Recommendations 11/30/2010)
c. Higher doses of vitamin D may be necessary for those with vitamin D levels less than 30 ng/mL.
d. Goal: 30 ng/mL in adults Selective estrogen receptor modulators Evista: Raloxifene
b. Indication: Prevention and treatment of osteoporosis in postmenopausal women
c. Mechanism: Selective estrogen receptor modulator
i. Reduction in resorption of bone
ii. Decrease in overall bone turnover
iii. Data suggest estrogen antagonist in uterine and breast tissue Efficacy:
i. Reduces the risk of vertebral fractures; reduces vertebral fractures by 30%–50%,
has not been shown to decrease hip fractures
ii. Lowers total cholesterol by 7% and LDL-C by 11%; does not reduce risk of CHD Adverse reactions:
i. Hot flashes: 6%–25%
ii. Leg cramps: 6%
iii. VTE: About 1% (hazard ratio 2.4 (95% CI, 1.2–4.5), 2- to 3-fold increased risk over placebo)
f. Dose: 60 mg/day orally
g. Contraindications
i. Pregnancy, nursing, pediatrics
ii. History of venous thromboembolic events; greatest risk of venous thromboembolic events
occurs during first 4 months
h. Drug interactions
i. Bile acid resins decreased raloxifene absorption by 60%.
ii. Warfarin: Prothrombin time is decreased by 10%.
iii. Thyroid hormones—Separate administration by 12 hours Calcitonin-salmon (Miacalcin)
a. Inhibition of bone resorption
b. Indicated for osteoporosis treatment of postmenopausal women for at least 5 years
c. Not a first-line drug; useful for bone pain caused by vertebral compression fractures
d. Efficacy: Nasal calcitonin reduced the incidence of new vertebral fractures by 36%.
e. Adverse effects
i. Nasal (10%–12%): Rhinitis, epistaxis, irritation, nasal sores, dryness, tenderness
ii. Other (3%–5%): Backache, arthralgia, headache
f. Drug interactions: None
g. Dosage: 200 IU/day in one nostril, alternating nostrils daily
i. 200 IU nasally = 50–100 IU by injection
ii. 200 IU per actuation, so one bottle will last about 2–3 weeks Teriparatide (Forteo)
a. Recombinant human parathyroid hormone regulates bone metabolism, intestinal calcium
absorption, and renal tubular calcium and phosphate reabsorption.
b. Efficacy
i. Reserved for treating women at high risk of fracture, including those with very low BMD
(T-score worse than 3.0) and a previous vertebral fracture
ii. Decreases vertebral fractures by 65% and non-vertebral fractures by 53%, not shown to
decrease hip fractures
c. Contraindications: Hypercalcemia, bone metastases, disorders that predispose women to bone
tumors such as Paget disease
d. Adverse effects: Nausea, orthostatic hypotension
e. Carcinogenicity: Osteosarcoma in rats
f. Drug interactions: Teriparatide increases calcium concentrations and may increase risk of digoxin
toxicity.
g. Dosage: 20 mcg/day subcutaneously Denosumab (Prolia)—Approved in 2010 for postmenopausal women with osteoporosis and bone loss
associated with prostate or breast cancer
a. Inhibits osteoclast-mediated bone resorption, monoclonal antibody against RANKL (receptor
activator of nuclear factor қ β ligand), cytokine essential for formation, function, survival of
osteoclasts
b. Administered subcutaneously every 6 months
c. Not contraindicated in patients with renal dysfunction
d. Efficacy
i. Increased BMD hip (6%) and spine (9%)
ii. Reduced spinal fracture risk by 68%, hip fracture risk by 40% e. Safety issues
i. Possible opportunistic infections
ii. Hypocalcemia: Patients should take calcium and vitamin D together with denosumab; those
with impaired renal function are more likely to have hypocalcemia.
iii. The FDA has risk evaluation and mitigation strategy requirements for this drug
(Medication Guide). Hormone therapy (estrogen and progestogens; see Hormone Therapy section above)
9. Lifestyle modifications
a. Weight-bearing exercise—Recommended; helps maintain bone strength
b. Smoking cessation—Smokers tend to have lower BMD scores
than nonsmokers and may reach menopause earlier Limiting alcohol intake—Affects fall risk, 2 or more units of alcohol
per day associated with 20% of falls at home according to one study.
No more than 2 units/day or 7 units/week is recommended.
d. Fall prevention
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