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2016 Endocrine > Test 1 Hormone Therapy > Flashcards

Test 1 Hormone Therapy Flashcards

1
Q

Menopausal transition

A
  • term used to define the years from the onset of the loss of ovarian cycling to her last menses
    • Transition between fertility and menopause
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2
Q

Menopause

A
  • cessation of menstruation following loss of ovarian function
    • Less than 1000 follicles left à ovarian function stops
    • No menstruation for 12 months
    • Average age is 51
  • Permanent cessation of menses following, or in association with, loss of ovarian follicular activity
    • Age
      • Ovaries stop working when there are < 1000 follicles
    • Ovaries removed
      • Will have hot flashes and night sweating
    • Uterus removed, but ovaries remain
      • No bleeding
      • Watch for symptoms to determine when they are going through menopause
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3
Q

Perimenopause

A
  • time in a woman’s life from the onset of her first symptom to loss of ovarian function thru 1 year after her last menses
    • Usually begins mid-late 40’s
  • Fluctuating estrogen levels
    • Women can still get pregnant - sometimes they will still ovulate
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4
Q

ET

A

estrogen therapy

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5
Q

EPT

A

combined estrogen-progestogen therapy

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6
Q

MHT

A

menopausal hormone therapy

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7
Q

Progestogen

A

· encompassing both progesterone and progestin

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8
Q

Perimenopause symptoms

A
  • Hot flashes
  • Night sweats
  • Cycle length begins to increase in the last 2 years of cycling
    • May extend to 80 – 90 days → progresses to 1 year
  • Anxiety, mood swings, depression
  • Disturbances in sexuality
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9
Q

Treatment of persistent or severe vasomotor symptoms in perimenopause

A
  • Low dose or Ultra-low dose BC pill
    • Estrogen helps with the symptoms
    • Protects them from getting pregnant
  • Post-menopausal estrogen (premarin)
    • Helps with symptoms
    • They could still get pregnant
      • Progestin-only contraceptive should be given if they have a uterus
  • Standard menopause treatment – premarin, prempro
    • Post-menopausal estrogen treatment
    • Will help symptoms, but won’t protect against pregnancy
  • Non-hormonal treatments
    • Will help with symptom relief
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10
Q

Menopause Diagnosis

A
  • Diagnosis (retrospective – diagnosis of exclusion)
    • Amenorrhea for 12 months with no other etiology
    • FSH and LH will be high (estrogen will be low → negative feedback → produce more FSH and LH to try to produce more estrogen)
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11
Q

Menopause Symptoms

A
  • Hot flashes (85%) / night sweats
    • If you can fix the hot flashes, many other symptoms will improve
  • Difficulty sleeping (50%)
  • Fatigue
  • Moodiness
  • Depression, anxiety
  • Decreased libido and orgasmic response
  • Changes in memory and cognition
  • Weight gain
  • Joint pain
  • Scalp hair loss
  • Hair growth or acne on face
  • Skin changes
  • Palpitations
  • Nausea
  • Headaches
  • Urinary tract infections
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12
Q

Menopause Nonhormonal Treatment of Vasomotor Symptoms

A
  • Lifestyle Modifications
  • OTC agents
  • Nonhormonal prescriptions
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13
Q

Menopause Nonhormonal Treatment of Vasomotor Symptoms:

Lifestyle Modifications

A
  • Fan
  • Chillow (chilled pillow)
  • Avoid spicy foods
  • Exercise
  • Meditation / yoga
  • Control breathing during hot flashes
  • Wear layers – take off as much as possible when a hot flash occurs
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14
Q

Menopause Nonhormonal Treatment of Vasomotor Symptoms:

OTC Agents

A
  • Soy isoflavones – active ingredient = genistein and daidzein
    • Conflicting data
    • Placebo effect is about 50%
    • Has some estrogenic activity – do not recommend for a woman with breast cancer
  • Black cohosh (Remifemin)
    • Largest randomized controlled trial showed no difference compared with placebo
    • Do not use for more than 6 months – hepatotoxicity
    • Weak estrogenic activity – do not recommend if there are contraindications to estrogen
  • No evidence of efficacy for hot flashes
    • Evening primrose oil
    • Chasteberry
    • Dong quai
    • Ginseng
    • Vitamin E
    • Kava
    • Wild yam
    • Red clover isoflavones
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15
Q

Menopause Nonhormonal Treatment of Vasomotor Symptoms:

Nonhormonal prescriptions

A
  • Clonidine
    • 0.05-0.1 mg/day or transdermal equivalent
    • Raises the sweating threshold (only for hot flashes)
      • Decreases hot flashes by 38%
    • Reasonable for woman who can’t take estrogen and has HTN
  • SSRIs and SNRIs – may be good for people who have depression or sleep issues. Well help with mood and hot flashes.
    • Paroxetine
    • Brisdelle (7.5 mg) – indicated for menopause
    • Fluoxetine
    • Venlafaxine
    • Dexvenlafaxine
  • Gabapentin
    • Originally studied in women with breast cancer and hot flashes
    • Takes high doses – 2400 mg or more
    • More side effects such as dizziness
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16
Q

Menopause Hormonal Agents for Vasomotor Symptoms:

Estrogen

A
  • Estrogen provides the hot flash / night sweat benefit (90% effective)
    • May be given in a woman who has had a hysterectomy (no uterus)
    • Gold-standard treatment
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17
Q

Menopause Hormonal Agents for Vasomotor Symptoms :

Estrogen/progestin therapy

A
  • Estrogen/progestin therapy
    • Progestin must be given in a woman with a uterus – estrogen-only will cause building of endometrium →endometrial cancer
  • Gold-standard treatment
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18
Q

Menopause Hormonal Agents for Vasomotor Symptoms:

HT

A
  • HT may have a slow onset of action
    • Should see some effects in a week but may take a month for full effectiveness to be seen
  • Abrupt discontinuation may worsen symptoms
    • Hot flashes may be worse than before
    • Taper dose – increase the interval between doses
  • Low doses can reduce hot flash frequency and severity almost as well as “conventional” doses
    • 0.625 premarin was the conventional dose
      • Only used if absolutely necessary
    • 0.3 – 0.45 are now used – still work
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19
Q

Menopuase Hormonal Agents for Vasomotor Symptoms :

Bioidentical Hormones

A
  • Bioidentical hormones
    • There is no data to support that they are safer than conventional therapy
    • They work, but the safety data is not there
    • No link between symptoms and saliva levels (often used for dosing guidance)
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20
Q

Hormonal Agents for Vasomotor Symptoms:

Contraindications

A
  • Contraindications to hormone therapy
    • Unexplained vaginal bleeding (may have cancer)
    • Acute liver dysfunction
    • Estrogen-dependent cancer
      • Breast cancer
    • Coronary heart disease
    • Stroke
    • Thromboembolic disease
    • Peanut allergy (micronized progesterone only)
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21
Q

Use ET for women?

A

who have undergone a hysterectomy

22
Q

Use EPT for women?

A

women with an intact uterus

23
Q

Estrogens

A
  • All are equally effective chose by patient preference and route desired
  • Initial dose - Start with a low dose
    • Oral, transdermal, percutaneous (and Femring) preparations are used to relieve moderate-to-severe vasomotor symptoms
    • Vaginal creams, tablets (and Estring – vaginal ring) are used to relieve urogenital atrophy - Do not give systemic therapy
  • Routes
    • Oral – most common
    • Transdermal/percutaneous – patches, gels, emulsions, sprays
      • Doesn’t affect SHB globulin as much
      • Less effect on cholesterol and clotting factors than oral formulation
    • Intravaginal – 2 rings
      • One for menopausal symptoms (hot flashes, night sweats)
      • One ring for urogenital symptoms
    • Intranasal and SQ (not currently available in US)
  • Benefits of bypassing the GI tract
    • Less effect on cholesterol and clotting factors
24
Q

Important and severe adverse effects of estrogens

A
  • Important adverse effects
    • DVT
    • Same as with contraceptives (estrogen component), but not as bad because it is a less potent estrogen
  • Severe adverse effects
    • Coronary heart disease, stroke, venous thromboembolism, breast cancer, gallbladder disease, endometrial cancer (must give with progestin if the patient has a uterus)
25
Q

Progestogens

A
  • Progestogens
    • Protect the uterus from endometrial cancer
    • Some creams do require progestogen therapy
      • Give with premarin cream
    • Minimum of 12-14 days each month is required
  • Progestogen Doses
    • Medroxyprogesterone acetate 5-10 mg x 12-14 days per month
    • Micronized progesterone 200 mg x 12-14 days per month
    • Norethindrone acetate 5 mg x 12-14 days per month
  • Do not give micronized progesterone to a patient with peanut allergy
26
Q

Progestogens Important Adverse Effects

A
  • Important adverse effects
    • Nausea
    • Weight gain
    • Bloating
    • Irritability
27
Q

Methods of EPT Administration

A
  • All regimens have daily estrogen administraion
  • Progestogen administraion varies
    • Continuous Cyclic (sequential): 12-14 days every month
    • Continuous Combined: Daily
    • Continuous Long-Cycle: 12-14 days every other month
    • Intermittent Combined (continuous pulsed): Repeated cycles of 3 days on, 3 days off
28
Q

Continuous cyclic

A
  • Continuous cyclic = estrogen daily + progestogen the last 12 -14 days
    • Will start menses after progestogen is stopped
    • Protects the endometrium
29
Q

Continuous combined

A
  • Continuous combined = estrogen + progestogen daily
    • No bleeding
    • Protects the endometrium
30
Q

Continuous long-cycle

A
  • Continuous long-cycle = estrogen daily + progestogen 12 – 14 days every other month
    • Only have 6 periods instead of 12
    • May or may not protect the endometrium (not known)
31
Q

Intermittent combined

A
  • Intermittent combined = estrogen daily + progestogen 3 days on, 3 days off
    • Decrease bleeding
    • May or may not protect the endometrium
32
Q

Conjugated Estrogens/Bazedoxifene

A
  • Duavee once daily
    • Conjugated estrogens 0.45 mg and bazedoxifene 20 mg
      • Bazedoxifene - estrogen antagonist in the endometrium (SERM)
      • Use in a patient with a uterus who is at risk for osteoporosis
      • Use if patient has a uterus and does not want to use progesterone due to possible breast cancer link
    • Reduced number and severity of hot flashes by 4 weeks and increased BMD at lumbar spine and hip by 12 months
  • Important adverse effects
    • Estrogen effects
      • Nausea, clotting
    • Muscle spasms
33
Q

Androgens

A
  • Methyltestosterone + esterified estrogens (Covaryx)
  • Used to relieve moderate-to-severe vasomotor symptoms in patients not improved with estrogen alone
    • Very small percentage of women
    • Severe hot flashes (not improved w/ estrogen) and decreased libido
  • Contraindications
    • Known or suspected androgen-dependent neoplasia (cancer)
    • Pregnancy or lactation
    • Many other contraindications
  • Important adverse effects
    • Hair growth, deepening of the voice, etc
    • Seen if a woman is taking too much (high doses)
34
Q

Genitourinary Atrophy – Symptoms localized to genitourinary tract:

Pathophysiology

A
  • Pathophysiology
    • Low estrogen levels
    • Vagina becomes less elastic (breaks down)
    • Vaginal dryness
    • Vaginal atrophy
  • Most common problems resulting from urogenital atrophy are:
    • Painful intercourse (dyspareunia)
    • Vaginal infections
35
Q

Genitourinary Atrophy – Symptoms localized to genitourinary tract:

Treatment

A
  • Replens Water-soluble and silicone-based lubricants
  • Topical Estrogens (ring, cream, suppository)
  • Oral estrogens
    • only use if they have hot flashes and genitourinary atrophy
  • Transdermal estrogens
    • don’t use for genitourinary symptoms
  • Ospemifene (Osphena)
36
Q

Genitourinary Atrophy – Symptoms localized to genitourinary tract:

Treatment

Replens

A
  • Water-soluble and silicone-based lubricants (Replens)
    • Provides symptomatic relief, but doesn’t fix the underlying cause – need estrogen
37
Q

Genitourinary Atrophy – Symptoms localized to genitourinary tract:

Treatment

Topical estrogens

A
  • Topical estrogens (ring, cream, suppository)
    • Takes about 6 weeks to see improvement in symptoms, full to fully restore
    • Certain creams require progestin if they have a uterus
38
Q

Genitourinary Atrophy – Symptoms localized to genitourinary tract:

Treatment

Ospemifeme

A
  • Ospemifene (Osphena)
    • Indicated for moderate-severe dyspareunia (painful intercourse)
    • Estrogen agonist on the vaginal tissue – will help rebuild it
  • Drug interactions
    • Inhibitor of 3A4 and 2C9
  • Common adverse effects
    • Increases Hot flashes
    • Leg cramps
    • May thicken the endometrial lining (don’t know the results yet)
39
Q

Treatment approach to Menopause:

Someone with menopausal symptoms

A
  • Are symptoms vasomotor +/- urogenital
    • Do they have homonal therapy contraindication?
      • Yes
        • Venlafaxine, paroxetine, megestrol acetate, clonidine, gabapentin
      • No
        • Hormone therapy at lowest effective dose
          • Uterus intact-EPT
          • No uterus-ET
  • OR
  • Are Symptoms Urogenital only
    • Vaginal estrogen preparations with low systemic exposure
40
Q

Treatment Approach to Menopause:

No menopause symptoms

A
  • Women at risk for osteoporosis
    • Calcium supplement (if dietary intake inadequate)
    • Vit D
    • Weight bearing exercise with
      • tibolone
      • a serm (raloxifene, basedoxifene, lasofoxifene)
      • other FDA approved osteoporosis preventing medications
    • Consider hormone therapy if alternate therapies are not appropriate or have adverse effects
  • Women with osteoporosis
    • Calcium supplement (if dietary intake inadequate)
    • Vit D
    • other FDA approved osteoporosis preventing medications
41
Q

Major Hormone Therapy Studies

A
  • PEPI
  • HERS
  • WHI-estrogen/progestogen arm
  • WHI – estrogen-alone arm
42
Q

Major Hormone Therapy Studies:

PEPI

A
  • PEPI (Postmenopausal Estrogen/Progestin Interventions Trial, 1996)
    • Significantly changed practice over the years
    • Patients: 596 postmenopausal women age 45-64 with an intact uterus
    • Design: 3 year, multicenter, randomized, double-masked, placebo-controlled trial
    • Intervention: 0.625 mg/day CEE or 0.625 mg/day CEE + progesterone
    • Results: If women take estrogen alone and have a uterus, they will get endometrial cancer.
  • Made it standard of care to give a woman progesterone if they have a uterus
43
Q

Major Hormone Therapy Studies:

HERS

A
  • HERS (Heart and Estrogen/progestin Replacement Study, 1998)
    • Patients: 2763 postmenopausal women (mean age 66.7 years) with coronary disease and an intact uterus
    • Design: 4 year, randomized, blinded, placebo-controlled secondary prevention trial
    • Intervention: 0.625 mg CEE + 2.5 mg MPA or placebo
    • Results: no reduction in heart disease (didn’t increase MI or cardiac death)
  • We should not be giving hormone therapy to women with heart disease
44
Q

Major Hormone Therapy Studies:

WHI – estrogen/progestogen arm

A
  • WHI – estrogen/progestogen arm (Women’s Health Initiative, 2002)
    • Patients: 16,608 postmenopausal women age 50-79 (mean age 63.3 years) who were generally healthy with an intact uterus
    • Design: 8.5 years (stopped early at 5.2 years) randomized controlled primary prevention trial
    • Intervention: 0.625 mg CEE + MPA 2.5 mg or placebo
  • Results:
    • Absolute excess risk per 10,000 person-years attributable to estrogen plus progestin were:
      • 7 more CHD events
      • 8 more strokes
      • 8 more PEs
      • 8 more invasive breast cancers
    • Absolute risk reductions per 10,000 person-years were:
      • 6 fewer colorectal cancers
      • 5 fewer hip fractures
  • Giving healthy women hormone therapy may actually cause harm – don’t give to everyone – risks may outweigh benefits
  • Younger women who are newly menopausal – it may be safe to take hormonal therapy at low doses for a few years
45
Q

Major Hormone Therapy Studies:

WHI – estrogen-alone arm

A
  • WHI – estrogen-alone arm (Women’s Health Initiative, 2004)
    • Patients: 10,739 postmenopausal women who were generally healthy with prior hysterectomy
    • Design: 8.5 years (stopped early at 6.8 years) randomized controlled primary prevention trial
    • Intervention: 0.625 mg CE or placebo
  • Results: similar to estrogen/progestogen arm
    • Breast cancer may be due to progestin
46
Q

Women with no moderate-severe hot flashes/night sweats BUT has genitourinry symptoms (vaginal dryness/pain with intercourse)

A
  • Free of breast, endometrial, and other hormone senitive cancers
    • Vaginal lubricants/mosturizers
    • low dose vaginal estrogen if inadequate response
    • Ospemifene-option for those that want non-estrogen oral tx (if no contraindications)
  • HAS breast, endometrial, and other hormone senitive cancers
    • Vaginal lubricants/mosturizers
47
Q

Women with no moderate-severe hot flashes/night sweats AND has no genitourinry symptoms (vaginal dryness/pain with intercourse)

A

Avoid Hormone therapy

48
Q

Women with moderate-severe hot flashes/night sweats AND has no breast or endometrial cancer, CHD, DVT, or HT contraindications

A
  • Assess ASCVD risk AND years since menopaus
    • If ASCVD risk is >10 % avoid HT
    • AND
    • If > 10 years since menopause avoid HT
  • For ASCVD 10 or lower and years since menopause 10 or lower
    • HT ok
    • Hystorectomy:estrogen alone
    • Uterus intact: estrohen plus progestogen
  • Duration (continued mod-severe symptoms)
    • patient preference
    • weigh baseline breast cancer risks
    • CVD
    • osteoporosis
49
Q

Women with moderate-severe hot flashes/night sweats BUT has breast or endometrial cancer, CHD, DVT, or HT contraindications

A
  • Are they free of SSRI/SNRI contraindications?
    • Yes
      • Consider low dose paroxetine or other wells studied SSRI/SNRIs (venlafaxine, escitalopram, others)
        • If adequate control-continue low dose
        • No adequate control consider gabapentin, pregabalin, clonidine
    • No
      • Avoid SSRI/SNRIs
      • Consider gabapentin, pregabalin, clonidine (if they aren’t contrindicated)
50
Q

55 year old female complains of dyspareunia. She is diagnosed with vaginal atrophy. She had a hysterectomy at age 48. What do you recommend?

A

· Estring (17b-estradiol) vaginal ring

· Not necessary to give systemic therapy

51
Q

What would you give a Patient with dyslipidemia

A

· Give transdermal patch – less effect on dyslipidemia

2016 Endocrine (19 decks)

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