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
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
- Age
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
4
Q
ET
A
estrogen therapy
5
Q
EPT
A
combined estrogen-progestogen therapy
6
Q
MHT
A
menopausal hormone therapy
7
Q
Progestogen
A
· encompassing both progesterone and progestin
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
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
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)
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
12
Q
Menopause Nonhormonal Treatment of Vasomotor Symptoms
A
- Lifestyle Modifications
- OTC agents
- Nonhormonal prescriptions
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
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
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
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
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
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
- 0.625 premarin was the conventional dose
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)
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)
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
Progestogens
* 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
Progestogens Important Adverse Effects
* Important adverse effects
* Nausea
* Weight gain
* Bloating
* Irritability
27
Methods of EPT Administration
* 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
Continuous cyclic
* Continuous cyclic = estrogen daily + progestogen the last 12 -14 days
* Will start menses after progestogen is stopped
* Protects the endometrium
29
Continuous combined
* Continuous combined = estrogen + progestogen daily
* No bleeding
* Protects the endometrium
30
Continuous long-cycle
* 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
Intermittent combined
* Intermittent combined = estrogen daily + progestogen 3 days on, 3 days off
* Decrease bleeding
* May or may not protect the endometrium
32
Conjugated Estrogens/Bazedoxifene
* 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
Androgens
* 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
Genitourinary Atrophy – Symptoms localized to genitourinary tract:
Pathophysiology
* 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
Genitourinary Atrophy – Symptoms localized to genitourinary tract:
Treatment
* 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
Genitourinary Atrophy – Symptoms localized to genitourinary tract:
Treatment
Replens
* Water-soluble and silicone-based lubricants (Replens)
* Provides symptomatic relief, but doesn’t fix the underlying cause – need estrogen
37
Genitourinary Atrophy – Symptoms localized to genitourinary tract:
Treatment
Topical estrogens
* 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
Genitourinary Atrophy – Symptoms localized to genitourinary tract:
Treatment
Ospemifeme
* 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
Treatment approach to Menopause:
Someone with menopausal symptoms
* 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
Treatment Approach to Menopause:
No menopause symptoms
* 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
Major Hormone Therapy Studies
* PEPI
* HERS
* WHI-estrogen/progestogen arm
* WHI – estrogen-alone arm
42
Major Hormone Therapy Studies:
PEPI
* 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
Major Hormone Therapy Studies:
HERS
* 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
Major Hormone Therapy Studies:
WHI – estrogen/progestogen arm
* 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
Major Hormone Therapy Studies:
WHI – estrogen-alone arm
* 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
Women with **no** moderate-severe hot flashes/night sweats **BUT** has genitourinry symptoms (vaginal dryness/pain with intercourse)
* 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
Women with **no** moderate-severe hot flashes/night sweats **AND** has no genitourinry symptoms (vaginal dryness/pain with intercourse)
Avoid Hormone therapy
48
Women **with** moderate-severe hot flashes/night sweats **AND** has **no** breast or endometrial cancer, CHD, DVT, or HT contraindications
* 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
Women **with** moderate-severe hot flashes/night sweats **BUT** has breast or endometrial cancer, CHD, DVT, or HT contraindications
* 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
55 year old female complains of dyspareunia. She is diagnosed with vaginal atrophy. She had a hysterectomy at age 48. What do you recommend?
· Estring (17b-estradiol) vaginal ring
· Not necessary to give systemic therapy
51
What would you give a Patient with dyslipidemia
· Give transdermal patch – less effect on dyslipidemia
