Hormone Replacement Therapy – Flashcards

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Perimenopause
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is the period immediately prior to menopause and the first year of menopause. It is characterized by menstrual cycle irregularity due to the increased frequency of anovulatory cycles
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Menopause
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Menopause is the permanent cessation of menses -usually defined as 12 consecutive months of amenorrhea. Menopause is the loss of ovarian function and subsequent hormonal deficiency.
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Symptoms of perimenopause and menopause
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-Vasomotor symptoms -Sleep disturbances -Mood changes-anxiety, depression, mood swings -Problems concentrating and memory -Atrophic vaginitis/genitourinary symptoms -Osteoporosis
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Vasomotor symptoms
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hot flushes and night sweats-- primarily characterized by the perception of intense heat (hot flash) and subsequent cooling by cutaneous vasodilation (skin flushing), perspiration, and chills. Also, may include headache, dizziness, palpitations, and sleep disturbances. Approximately 75-85% of women are affected with vasomotor symptoms.
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Symptoms are associated with circadian rhythm and are worse in ______________ and _________.
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early morning and evening
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Symptoms can range from
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being a minor nuisance to being severe and disruptive to daily living.
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Vasomotor symptoms occur due to
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a transient lowering of the hypothalamic temperature regulatory set point.
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Typically, vasomotor symptoms occur ___ -___ years of menopause. Only 25% of women have vasomotor symptoms for more than __ years.
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1-2 years 5 years
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Atrophic vaginitis/genitourinary
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Urogenital atrophy is caused by estrogen loss because the urogenital tissues (vagina, vulva, urethra, and bladder) contain a large number of estrogen receptors. Atrophy results in thinning of tissue and loss of elasticity.
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Genital symptoms include
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dryness, burning, dyspareunia, loss of vaginal secretions, and vulvar pruritus.
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Over time, lack of vaginal lubrication may lead to _____________ and _______________.
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sexual dysfunction and emotional
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Urinary symptoms
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include urethral discomfort, frequency, dysuria, stress incontinence, and increased urinary tract infections.
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Urogenital atrophy occurs in at least ___ % of postmenopausal women.
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50
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Osteoporosis is associated with _____________and ____________.
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low bone mass increased fracture risk.
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Risk factors for osteoporosis include_____________ and _____________________.
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being female postmenopausal Approximately 40% of postmenopausal women have osteopenia and 7% have osteoporosis.
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Signs of perimenopause
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dysfunctional uterine bleeding
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Signs of menopause
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signs of urogenital atrophy
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FSH level that is indicative of perimenopause
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FSH on day 2 or 3 of the menstrual cycle is >10-12 milliinternational units/mL
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FSH level that is indicative of menopause
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FSH > 40 milliinternational units/mL
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Hormone therapy (HT)
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refers to estrogen with or without progestins.
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Clinical evidence of efficacy of hormone therapy shows
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a reduction in fracture, but an increase in breast cancer, CHD (during the first year), stroke, and DVT/PE. The benefit versus risk assessment has been altered in light of this newer evidence.
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In the absence of contraindications, hormone therapy is indicated (approved indications) for women with
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vasomotor symptoms (hot flushes and night sweats) and urogenital atrophy and prevention of osteoporosis
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The most effective drug intervention for vasomotor symptoms
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Systemic hormone therapy
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_____________ products should be considered for symptoms of urogenital atrophy.
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Intravaginal
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Transdermal patch (Menostar®) or the nonestrogen products (raloxifene and bisphosphonates) should be considered for
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osteoporosis prevention
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Hormone replacement therapy is contraindicated in women with
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endometrial cancer, breast cancer, undiagnosed vaginal bleeding, coronary heart disease, thromboembolism, stroke or transient ischemic attack and active liver disease.
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Relative contraindications to HRT
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uterine leiomyoma, migraine headaches, and seizure disorders
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____________ should be avoided in women with hypertriglyceridemia, liver disease, and gallbladder disease.
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Oral estrogen Transdermal administration is safer.
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Primary reasons for stopping hormone therapy are side effects such as
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bleeding, breast tenderness, bloating, and "premenstrual-like symptoms".
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Interventions to decrease side effects of HRT
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Reducing the dose or changing the regimen or the route of administration can minimize these effects
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If a woman is menopausal with only urogenital symptoms the treatment recommended is
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Vaginal estrogen preparation with low systemic exposure
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If a woman is menopausal with vasomotor symptoms +/- urogenital symptoms without contraindications the treatment recommendation is
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Consider estrogen/progestogen or estrogen alone (in women with hysterectomy). Use lowest effective dose and for the shortest duration -Reassess yearly
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If a woman is menopausal with vasomotor symptoms +/- urogenital symptoms with contraindications the treatment recommendation is
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Consider venlafaxine, paroxetine, megestrol acetate, clonidine, gabapentin -Reassess yearly
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Treatment recommendation for a woman that is not menopausal and asymptomatic but at risk for osteoporosis
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Calcium, vitamin D and exercise with a bisphosphonate or raloxifene. Estrogen + progestogen or estrogen alone (in women with hysterectomy) should be given only if the benefits clearly outweigh the risks -Reassess yearly
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Treatment recommendation for a woman that is not menopausal but has osteoporosis
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Calcium and vitamin D with a bisphophonate, teriparatide (for women at high risk of fracture), or possibly calcitonin -Reassess yearly
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Drug treatment of first choice
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Hormone therapy is the most effective treatment option for alleviating vasomotor and vaginal symptoms.
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In women with an intact uterus, hormone therapy consists of
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an estrogen plus a progestogen.
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In women who have undergone hysterectomy, estrogen therapy is given
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unopposed by a progestogen.
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Most women require HT for < __ years so the risks of HT appear ________.
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5 small -If treatment can be tapered and stopped within 5 years there is no evidence of increased risk of breast cancer seen.
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_____________ has been shown to be as effective as estrogen therapy in alleviating significant vasomotor symptoms
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No therapy
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Estrogens diminish _____ _________ in most women, and all types and routes of administration of estrogen are equally effective.
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hot flushes
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Alternatives to estrogen for treatment of hot flushes include
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paroxetine, venlafaxine, fluoxetine (commonly used antidepressants), medroxyprogesterone acetate, megestrol acetate, clonidine (antihypertensive), and gabapentin (an anticonvulsant; also used for treatment neuropathies)
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Atrophy of the vaginal mucosa results in ______________ and ______________.
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vaginal dryness and dyspareunia.
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Lower urinary tract symptoms include
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urethritis, recurrent urinary tract infection, urinary urgency, and frequency.
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Women with significant vaginal dryness require _____________ estrogen therapy for symptom relief.
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local or systemic
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For local estrogen therapy treatment, consider treatment with
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intravaginal estrogen cream, tablet, or ring.
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____________ is better than __________ estrogen for relieving these symptoms
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Vaginal estrogen systemic estrogen -and avoids high levels of circulating estrogen.
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If women are using low dose micronized 17β-estradiol then concomitant progestogen therapy is usually (necessary/not necessary)?
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not necessary.
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If women are using conjugated equine estrogens (CEE) vaginal creams and other products that can promote endometrial proliferation in women with an intact uterus then they require
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intermittent progestogen challenges (for 10 days every 12 weeks).
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Vaginal atrophy requires
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long-term estrogen treatment.
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Urinary incontinence (is/is not) improved by estrogen therapy.
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is not
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Prevention of osteoporosis is _____-term.
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long
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For prevention of osteoporosis, the advantages of hormone therapy must be weighed against the risks, including ___________and increased incidence of _________________ and ___________cancer and consideration should be given to approved nonestrogen alternatives.
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thrombosis cardiovascular disease breast
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Prevention remains an indication for estrogen products but
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the FDA withdrew the indication for osteoporosis treatment.
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________________ are as effective as hormone therapy for preventing osteoporosis.
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Bisphosphonates
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_______________ is no longer considered first-line therapy for prevention of osteoporosis because of the risks associated with its long-term use.
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Long term HT
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HT should not be continued or initiated for prevention of ______________ ______________.
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cardiovascular disease -Major US trials provided evidence of no protection from cardiovascular disease and some evidence of harm
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Combination estrogen and progestin has been shown to increase ___________________ in the first year of therapy and resulted in no difference in CHD events in remaining years.
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coronary heart disease
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________________ may be tried prior to initiating drug therapy.
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Lifestyle modifications
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Herbal therapies that have estrogenic mechanisms should be used with
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caution in patients who would have contraindications for estrogens.
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Menopausal lifestyle modifications: wearing layered clothing
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(to remove and add layers as needed)
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Menopausal lifestyle modifications: Avoiding triggers
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(such as warm environments, caffeine, hot beverages, stress, alcohol, spicy foods)
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Menopausal lifestyle modifications:Exercise
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Exercising for as little as 1-2 hours/week has shown benefit. The mechanism for this is an increase in production of β-endorphin which is the primary neurotransmitter responsible for thermoregulation.
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If __________ symptoms are present, symptoms will often be alleviated by lifestyle modifications.
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only mild
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Black cohosh mechanism
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weak estrogenic activity and possible serotonergic effects
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Black cohosh AEs
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gastrointestinal discomfort and rash, concern of similar risks to estrogen, potential for liver damage
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Black cohosh dose
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39-127 mg daily PO
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Black cohosh efficacy
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Inconsistent results have been observed in clinical trials.
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Soy protein mechanism of action
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Plant compound with estrogen-like biologic activity and relatively weak estrogen receptor binding properties.
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________________ has the most estrogenic activity.
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Isoflavones (soy protein)
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Soy protein AEs
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gastrointestinal symptoms, concern of similar risks to estrogen
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Soy protein dose
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34-93 mg daily PO
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Soy protein efficacy
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Inconsistent results have been observed in clinical trials.
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Premarin route
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oral, intravaginal cream
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Estrace route
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oral, intravaginal cream
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Vivelle Dot route
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transdermal patch
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Menostar route
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transdermal patch
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Estring route
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Intravaginal
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Vagifem route
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Intravaginal
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Divigel route
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Dermal
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Evamist route
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Dermal
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The most effective formulation of estrogen therapy
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In general, there is no evidence that one formulation is any better than another.
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The ________ and _________ should be selected taking into consideration the patients' preference to ensure acceptability and enhance compliance.
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product and delivery method
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______________ HT avoids first-pass metabolism because it bypasses the gastrointestinal tract. Thus, eliminates the risk of gallbladder disease and may be beneficial for patients with elevated triglycerides.
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Topical HT (including transdermal and dermal)
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Low doses (i.e. 0.3 mg CEE) have been shown to be effective in controlling _____________ and ________________.
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postmenopausal symptoms and reducing bone loss.
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Low doses may be safer than standard doses. However, the safety of low-dose estrogen and intravaginal estrogen has not been
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evaluated in long-term studies. Low doses are now recommended due to the long-term risks of standard doses. Dosing should start low and titrate slow.
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If intolerable adverse effects occur, consider ____________ or ______________.
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adjusting dose down try alternative formulation (compound or route).
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If symptoms are not controlled, then consider
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increasing dose upward.
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Women who have not undergone hysterectomy should be treated
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concurrently with a progestogen in addition to the estrogen.
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Four combination estrogen and progestogen regimens currently in use are
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1. continuous cyclic (sequential), 2. continuous combined, 3. continuous long-cycle (or cyclic withdrawal), and 4. intermittent combined (or continuous pulsed) hormone therapy.
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Sequential hormone therapy results in ___________ vaginal withdrawal bleeding but is very ______ or _______ in older women.
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scheduled light or absent
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New hormone therapy regimens that reduce monthly bleeding (________________) or prevent monthly bleeding (___________________ ) have been developed
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continuous long-cycle continuous combined and intermittent combined
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Sequential hormone therapy
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Estrogen given daily Progestin given 12-14 of 28 day cycle
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Sequential hormone therapy comments
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Withdrawal bleeding occurs 1 to 2 days after last MPA dose
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Continuous combined hormone therapy
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Estrogen and progestogen given together daily
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Continuous combined hormone therapy comments
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Causes unpredictable spotting or bleeding -usually resolves in 6-12 months.
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Continuous long-cycle hormone therapy
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Estrogen given daily; progestogen given 6 times/year for 12-14 days
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Continuous long-cycle hormone therapy comments
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Results in bleeding 6 times/year
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Intermittent combined or continuous pulsed or pulsed progestogen hormone therapy
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Estrogen given for 3 days followed by 3 days of estrogen plus progestogen repeated continuously
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Intermittent combined or continuous pulsed or pulsed progestogen hormone therapy comments
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Lower incidence of uterine bleeding; lower progestogen dose produces lower side effects
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Risks of sequential hormone therapy
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The risks of hormone therapy include ovarian cancer, endometrial cancer, breast cancer, venous thromboembolism, gallbladder disease, increase in blood pressure, stroke, and possibly cardiovascular disease in older women
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Adverse effects of sequential hormone therapy: estrogen
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nausea, bloating, headaches, breast tenderness, edema.
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Adverse effects of sequential hormone therapy: progestin
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increased appetite, weight gain, fatigue, hypomenorrhea, acne, oily scalp, hair loss, hirsutism, depression, irritability, headaches.
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Adverse effects of sequential hormone therapy: transdermal
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Application site reactions in 5-10% of women. Transdermal therapy has been shown to be less likely to cause nausea and headache versus oral therapy.
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Benefits of androgen HRT
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improved libido and bone mass in perimenopausal and postmenopausal women with androgen deficiency.
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Symptoms of androgen deficiency are more pronounced in women with ___________ _____________, and use of androgen is generally accepted in this population.
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surgical menopause --Androgen use is becoming more acceptable in women with natural menopause.
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_____________ therapy combined with an androgen significantly improves sexual activity, satisfaction, and pleasure (more than with ________ alone.)
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Estrogen estrogen
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Androgen HRT efficacy
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Androgen therapy has been shown to be effective and safe if given in doses to achieve concentrations within the normal physiologic range. Data is not available on fracture or breast cancer risks.
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The most appropriate candidates for consideration of estrogen plus androgen therapy include:
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women who have had their ovaries removed and those with sexual dysfunction especially loss of libido.
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Androgen HRT should always be co-adminstered with _____________ in postmenopausal women
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estrogen
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Oral methyltestosterone
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i. Most studied androgen in postmenopausal women ii. Dosing: 1.25-2.5 mg PO QD iii. Combination products with estrogen: Estratest®, Syntest® Other dosage forms include intramuscular, subcutaneous, and transdermal.
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Androgen HRT AEs
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virilization, fluid retention, adverse lipid effects
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Androgen HRT contraindications
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moderate to severe acne, clinical hirsutism, androgenic alopecia, and androgen-dependent neoplasia
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