Clinician's Guide Menopause Practice Chapter 11 Flashcards
(264 cards)
1
Q
What types of hormone drugs are considered for women during perimenopause?
A
Prescription hormone drugs, including contraceptives, hormone therapy (HT), androgens, and estrogen agonists/antagonists, and nonprescription, over-the-counter (OTC) hormones.
These treatments are used to manage symptoms associated with perimenopause and beyond.
2
Q
What should be considered for women with premature or early menopause?
A
Hormone therapy (HT) until the average age of menopause to prevent health consequences of estrogen loss.
This includes natural, induced, or surgical menopause.
3
Q
What have numerous clinical trials shown about hormone therapy (HT)?
A
HT is effective in preventing osteoporosis and reducing the risk of fractures.
4
Q
What is the benefit of low-dose vaginal estrogen for women with genitourinary syndrome of menopause (GSM)?
A
It can be used at any age with benefit and minimal risk without the need for opposing progestogen therapy.
5
Q
What is the status of testosterone therapy for postmenopausal women in the U.S. and Canada?
A
There are no FDA-approved testosterone therapies for this use.
6
Q
What are the risks associated with compounded, non-FDA approved therapies?
A
Lack of rigorous safety and efficacy testing, lack of government regulation, concerns about batch standardization, overdosing or underdosing, and purity and sterility concerns.
7
Q
What should perimenopausal women who wish to avoid pregnancy be counseled about?
A
Various birth control methods.
8
Q
What factors influence contraceptive choice in perimenopausal women?
A
Symptoms of perimenopause, concomitant medical conditions, and the desire for long-acting or permanent contraception.
9
Q
What are effective contraceptive options for perimenopausal women?
A
Hormonal contraceptives (HCs), including those with and without estrogen, and intrauterine devices (IUDs).
10
Q
What are long-acting reversible contraceptive methods?
A
Copper IUD, levonorgestrel-releasing intrauterine systems (LNG-IUS), and etonogestrel subdermal implant.
11
Q
What are the CDC guidelines for contraceptive use?
A
US Selected Practice Recommendations for Contraceptive Use (SPR) and US Medical Eligibility Criteria for Contraceptive Use (MEC).
12
Q
What does the MEC categorize contraceptive methods based on?
A
Safety when used in women with various medical conditions.
13
Q
What are the four categories of contraceptive eligibility according to MEC?
A
- No restriction for use
- Advantages generally outweigh risks
- Risks usually outweigh advantages
- Unacceptable health risk if used.
14
Q
True or False: There are contraceptive methods contraindicated based solely on age.
A
False.
15
Q
What is a common adverse effect of using intrauterine contraception (IUD)?
A
Irregular uterine bleeding and spotting.
16
Q
What is the effectiveness duration of the 52-mg LNG-IUS in the U.S.?
A
Approved for 5 years but remains effective for up to 7 years.
17
Q
What is a noncontraceptive use of the 52-mg LNG-IUS?
A
To prevent bleeding and endometrial hyperplasia in postmenopausal women using estrogen therapy.
18
Q
What is the amenorrhea rate at 1 year for the 19.5-mg LNG-IUS?
A
19%.
19
Q
What is the principal adverse effect associated with the copper IUD?
A
Increased cramping and menstrual flow.
20
Q
What is the risk of uterine perforation during IUD insertion?
A
Approximately 1 per 1,000 insertions.
21
Q
What are the routes of delivery for progestin-only contraceptives?
A
- IUD
- Subdermal implant
- Injection
- Oral contraceptives (OCs).
22
Q
What is the effect of progestin-only contraceptives on menstrual bleeding?
A
They decrease menstrual bleeding and menstrual-related disorders.
23
Q
What type of contraceptive is depot MPA?
A
A progestin-only injectable contraceptive.
24
Q
How often is depot MPA administered?
A
Every 3 months.
25
What is a potential delay for return of fertility after stopping depot MPA?
12 to 18 months.
26
What is the blood pressure threshold for hypertension?
Systolic ≥160 mm Hg or diastolic ≥100 mm Hg
## Footnote
Hypertension is often defined by these measurements.
27
What are the risks associated with vascular disease or diabetes mellitus (DM) lasting more than 20 years?
Risks outweigh benefits
## Footnote
This applies to certain medical decisions regarding treatment.
28
What is the common side effect after four or more injections of an injectable progestin-only contraceptive?
Amenorrhea
## Footnote
At least one-half of users may experience this.
29
What is the primary use of injectable DMPA?
Contraception and treatment of endometriosis-related pain
## Footnote
DMPA is a form of depot medroxyprogesterone acetate.
30
What type of contraceptive is norethindrone 0.35 mg formulated for?
Progestin-only oral contraceptive
## Footnote
It is effective for perimenopausal women.
31
What increases the risk of serious cardiovascular adverse events (AEs) from hormonal contraceptive use?
Cigarette smoking
## Footnote
The risk increases with age and amount smoked.
32
What is a relative contraindication for combination contraceptives in perimenopausal women?
Obesity
## Footnote
This is particularly relevant for women with a BMI greater than 30.
33
What are some noncontraceptive benefits of combination oral contraceptives?
* Regulation of irregular uterine bleeding
* Reduction of vasomotor symptoms (VMS)
* Decreased risk of ovarian and endometrial cancer
* Maintenance of bone density
## Footnote
These benefits are particularly noted in healthy, non-smoking women.
34
What is the typical regimen for newer OC formulations?
24/4 regimen
## Footnote
This consists of 24 active pills followed by 4 inactive pills.
35
What is unique about drospirenone compared to other synthetic progestins?
It is derived from 17α-spironolactone
## Footnote
Drospirenone has mild antimineralocorticoid effects.
36
What is the potential risk associated with drospirenone-containing OCs?
Increased risk of venous thromboembolism (VTE)
## Footnote
Some studies suggest a 3-fold increase compared to other progestins.
37
What is the main advantage of extended oral contraceptive formulations?
Less frequent withdrawal bleeding
## Footnote
These regimens can reduce menstrual symptoms.
38
What is the primary function of emergency contraception?
Prevent pregnancy after unprotected intercourse
## Footnote
It does not serve as a primary contraceptive method.
39
What is the most effective form of emergency contraception?
Copper IUD
## Footnote
It is more than 99% effective when used as emergency contraception.
40
What distinguishes emergency contraception from the abortion pill?
Emergency contraception prevents fertilization, while the abortion pill terminates an existing pregnancy
## Footnote
Emergency contraception is classified as contraception.
41
What is the role of UD in contraception?
UD may inhibit fertilization and implantation and then can remain in place as long-acting reversible contraception.
42
How are emergency contraception methods classified medically?
They are considered forms of contraception according to the International Federation of Gynecology and Obstetrics and the US government.
43
What is the active ingredient in the progestin-only emergency contraception formulation approved in the US and Canada?
LNG (levonorgestrel) as two 0.75-mg tablets taken 12 hours apart or as a single 1.5-mg dose.
44
What is the efficacy of progestin-only emergency contraception if taken within 72 hours after coitus?
Reduces the risk of pregnancy by 88%.
45
What is ulipristal acetate (UPA) and how is it used?
UPA is a progesterone receptor modulator used as soon as possible and up to 5 days after unprotected sex.
46
True or False: Emergency contraception is effective in women who are already pregnant.
False.
47
What are some noncontraceptive benefits of hormone contraceptives for perimenopausal women?
* Restoration of regular menses
* Decreased dysmenorrhea
* Reduced heavy menstrual bleeding
* Reduced pain associated with endometriosis
* Suppression of VMS
* Enhanced BMD and possible prevention of osteoporotic fractures
* Decreased need for biopsies for benign breast disease
* Prevention of epithelial ovarian and endometrial malignancies
* Improvements in acne
48
What is the median age of menopause for nonsmoking women?
Approximately 52 years.
49
What should be considered when transitioning from hormone contraception to hormone therapy?
Ensure menopause is reached to minimize hormone-related risks.
50
What does estrogen therapy encompass?
* ET (estrogen therapy)
* EPT (combined estrogen-progestogen therapy)
* Progestogen alone
* Estrogen combined with an estrogen antagonist/agonist
51
What are the three categories of estrogen-containing drugs for menopause symptom use?
* ET (estrogen therapy)
* EPT (combined estrogen-progestogen therapy)
* ET combined with an estrogen agonist/antagonist
52
What are the main types of human estrogens?
* Estrone
* 17β-estradiol (estradiol)
* Estriol
53
What are conjugated equine estrogens (CEE)?
A mixture of at least 10 active estrogens obtained from the urine of pregnant mares.
54
What is the primary source of estrogen in normally cycling adult women?
The ovarian follicle.
55
What happens to estrogen production after menopause?
Most endogenous estrogen is produced by conversion of androstenedione to estrone by peripheral tissues.
56
What is estetrol and when is it synthesized?
A natural estrogen synthesized exclusively during pregnancy by the human fetal liver.
57
What is the significance of estrogen receptors in the body?
Estrogen receptors are present in almost all cells and are responsible for the development and maintenance of the female reproductive system and secondary sex characteristics.
58
Fill in the blank: Estrogen therapy acts to reduce elevated levels of ______ in postmenopausal women.
gonadotropins
59
What is the role of estrogen in bone growth?
Stimulates bone growth during puberty and helps close the bony epiphyses.
60
What is the effect of estrogens on the release of pituitary gonadotropins?
Regulates the secretion through a negative-feedback mechanism.
61
What is Estetrol and its primary source?
A very weak estrogen produced exclusively during pregnancy by the human fetal liver
## Footnote
Estetrol is considered to have dose-dependent estrogenic effects on various parameters.
62
What are the clinical effects of Estetrol?
Agonist effects on relief of menopause symptoms, bone, vagina, arteries, and uterus
## Footnote
Estetrol is tissue selective with minimal effects on coagulation.
63
What must Estetrol be combined with if developed as hormone therapy?
A progestogen for uterine protection
## Footnote
This is necessary due to its agonist effect in the uterus.
64
Is Estetrol FDA approved in the United States?
No
## Footnote
It is not currently FDA approved for use.
65
How are estrogens absorbed when used in oral estrogen therapy?
Well absorbed from the gastrointestinal tract
## Footnote
Maximal plasma concentrations are attained 4 to 10 hours after administration.
66
What is the half-life of estradiol when administered orally?
Approximately 16 hours
## Footnote
The half-life for transdermal estradiol is 4 to 8 hours.
67
What does sex hormone-binding globulin (SHBG) bind with greater affinity?
DHEA than testosterone
## Footnote
SHBG influences the ratio of bound to unbound steroids.
68
What happens to free testosterone levels with increased SHBG?
They decrease
## Footnote
This occurs particularly with oral estrogen and other factors like insulin resistance.
69
What is the first-pass effect in relation to estrogens?
Rapid metabolism in the gut and liver before reaching general circulation
## Footnote
This decreases the amount of estrogen available for circulation.
70
What is a key characteristic of synthetic estrogens like ethinyl estradiol?
Degraded very slowly in the liver and other tissues
## Footnote
This accounts for their high potency.
71
What is the effect of nonoral routes of administration of estrogens?
Not subject to first-pass metabolism
## Footnote
They undergo significant hepatic uptake, metabolism, and enterohepatic recycling.
72
What are the marketed forms of estrogens available?
Single agents, transdermal patches, gels, topical emulsions, vaginal preparations, combination EPT preparations
## Footnote
Clinicians should refer to product labeling before prescribing.
73
What is the primary indication for all government-approved estrogen-containing products in the US?
Treatment of moderate to severe vasomotor symptoms (VMS)
## Footnote
Local vaginal ETs are indicated for moderate to severe vaginal dryness and symptoms of GSM.
74
What is the standard daily dose for conjugated estrogens (CEE)?
0.625 mg daily
## Footnote
This is based on bone protection studies.
75
What has been observed about breast cancer risk in CE users compared to placebo?
Decreased risk
## Footnote
This was noted in a 10.7-year follow-up study after the WHI Estrogen-Alone trial.
76
What is the significance of the first-pass metabolism of estrogens?
It affects liver functions and lipid profiles differently
## Footnote
This is one reason various routes of administration have different effects.
77
What are esterified estrogens and their primary composition?
Oral products containing 75% to 85% sodium estrone sulfate
## Footnote
They are not indicated for osteoporosis.
78
What is the equivalent dose of oral micronized estradiol (ME) to CE for liver function effects?
1.0 mg of ME is equivalent to 0.625 mg of CE
## Footnote
There are significant differences in metabolic pathways and adverse effects.
79
How can estrogen be administered?
Orally, transdermally, topically, or vaginally
## Footnote
Intramuscular preparations are not recommended due to high serum levels.
80
What effect does oral estrogen therapy have on triglycerides?
About a 25% increase
## Footnote
This increases the risk of pancreatitis in women with existing hypertriglyceridemia.
81
What is the dosage of Divigel for transdermal delivery?
0.1 mg/day
## Footnote
Divigel is a transdermal estrogen therapy product.
82
What are the two main types of estrogen therapy delivery methods?
Transdermal/Topical and Vaginal
## Footnote
These methods are used for delivering estrogen to treat menopause symptoms.
83
What is a notable advantage of transdermal estrogen administration over oral administration?
Lower doses required due to no dependence on GI absorption or first-pass hepatic metabolism.
84
True or False: Transdermal estrogen increases triglycerides (TG).
False
## Footnote
In contrast to oral estrogen therapy, transdermal does not increase TG.
85
What is a disadvantage of transdermal estrogen compared to oral estrogen?
Does not increase HDL-C.
86
Why might transdermal estrogen be preferred for stable estrogen levels?
It is associated with relatively stable serum levels.
87
What is the first transdermal patch approved for use in the United States?
Estraderm
88
What are some forms of transdermal estrogen available?
Patches, gels, sprays, and topical emulsions.
89
What is a clinical concern regarding transdermal gel and emulsion products?
Skin-to-skin contact can lead to person-to-person transfer of estradiol.
90
What was the finding of the Estrogen and Thromboembolism Risk trial?
Oral ET is associated with an increase of VTE, while transdermal ET is not.
91
How many women participated in the Kronos Early Estrogen Prevention Study?
727
92
What are the methods of vaginal estrogen delivery?
Creams, rings, tablets, and inserts.
93
True or False: Vaginal estrogens are typically used for systemic effects.
False
## Footnote
Vaginal estrogens are primarily used for local effects, except for specific products like Femring.
94
What should be considered when determining the estrogen delivery route for a woman?
Individual needs and preferences.
95
What is the primary use of progestogen therapy in menopause treatment?
To reduce the risk of endometrial cancer associated with unopposed estrogen.
96
What does the term 'progestogen' include?
Progesterone and synthetic progestational compounds called progestins.
97
What is the difference between progesterone and progestins?
Progesterone is identical to endogenous hormone; progestins are synthetic and not identical.
98
What are two classifications of progestins based on their structure?
Pregnane derivatives and 9-norpregnane derivatives.
99
What is the primary action of progestogens in the uterus?
Function primarily as antiestrogens, decreasing the number of nuclear ERs.
100
Fill in the blank: The dosage of the 17β-estradiol matrix patch can range from _______ mg.
0.025 to 0.1
101
What is the dosage of estradiol for the vaginal tablet Imvexxy?
4 µg and 10 µg.
102
What is the release rate of the device containing 2 mg for GSM?
7.5 µg/d for 90 days
## Footnote
GSM stands for genitourinary syndrome of menopause.
103
What are the dosages of estradiol acetate released by devices containing 12.4 mg or 24.8 mg?
* 0.05 mg/d for 90 days
* 0.10 mg/d for 90 days
104
What are estradiol-containing products considered?
Bioidentical
105
What is the initial and maintenance dosage for a tablet containing 10 µg of estradiol hemihydrate for GSM?
* Initial: 1 tablet/d for 2 weeks
* Maintenance: 1 tablet 2x/week
106
What is the most commonly used progestogen formulation for endometrial protection in US women?
Oral progestin MPA (medroxyprogesterone acetate)
107
What are the distinct actions of different progestogen types?
* Varying adverse effects (AEs)
* Different actions on the endometrium and other organ systems
108
What is micronized progesterone (MP) structurally related to?
Progesterone
109
What should be avoided by women allergic to peanuts when using Prometrium?
Prometrium or its generic
110
What are the potential effects of oral progesterone?
* Mildly sedating effects
* Reduces wakefulness
111
What is the recommended dosage for micronized progesterone to significantly decrease VMS?
300 mg nightly
112
What are the formulations of micronized progesterone available?
* Cream
* Lotion
* Gel
* Oral capsule
* Suppositories
113
What should topical cream or gel preparations with progesterone not be used for?
Endometrial protection from unopposed estrogen
114
What is the release rate of the Mirena IUS?
20 µg/d
115
What are the benefits of progestin-releasing IUS?
* Delivers progestin in the highest concentration
* Effective for endometrial protection
116
What is the goal of estrogen-progestogen therapy (EPT) regimens?
* Provide uterine protection
* Maintain estrogen benefits
* Minimize adverse effects
117
What are the classifications of EPT regimens?
* Continuous-cyclic sequential
* Continuous cyclic long-cycle
* Continuous-combined
* Intermittent-combined
118
What happens in continuous-cyclic (sequential) EPT therapy?
Estrogen is used every day with progestogen added cyclically for 12 to 14 days each month
119
What is the outcome of using standard doses of estrogen with progestogen?
Uterine bleeding occurs in about 80% of women when progestogen is withdrawn
120
What is the incidence of endometrial hyperplasia in women using continuous-combined EPT preparations?
Generally less than 1%
121
What is the recommended monitoring when using a long-cycle regimen of EPT?
Endometrial monitoring is mandatory
122
What is a key concern when using long-cycle EPT regimens?
Risk of hyperplasia and bleeding
123
What is the dosage of CE (conjugated estrogen) typically used in continuous-cyclic EPT?
0.625 mg/d
124
What does the abbreviation MPA stand for?
Medroxyprogesterone acetate
125
What are common side effects associated with synthetic progestins?
* Mood changes
* Other adverse effects
126
What is the composition of Activelle LDb?
0.5 mg E + 0.1 mg P (1 tablet)
## Footnote
E stands for 17β-estradiol and P stands for progestogen.
127
What is the composition of Activelleb?
1 mg E + 0.5 mg P (1 tablet)
## Footnote
E stands for 17β-estradiol and P stands for progestogen.
128
What are the available dosages for Angeliq?
0.5 mg E + 0.25 mg P and 1 mg E + 0.5 mg P (1 tablet each)
## Footnote
E stands for 17β-estradiol and P stands for progestogen.
129
Describe the Oral intermittent-combined regimen.
E alone for 3 days, followed by E + P for 3 days, repeated continuously
## Footnote
E represents 17β-estradiol and P represents progestogen.
130
What is the composition of Prefesta?
1 mg E + 0.09 mg P (2 tablets)
## Footnote
E stands for 17β-estradiol and P stands for progestogen.
131
What is the composition of CombiPatch?
0.05 mg E + 0.14 mg P (9 cm2 patch, twice/week)
## Footnote
E stands for 17β-estradiol and P stands for norethindrone acetate.
132
What is the composition of Estalis?
0.05 mg E + 0.25 mg P (16 cm2 patch, twice/week)
## Footnote
E stands for 17β-estradiol and P stands for progestogen.
133
What is the composition of Climara Pro?
0.045 mg E + 0.015 mg P (22 cm2 patch, once/week)
## Footnote
E represents 17β-estradiol and P represents levonorgestrel.
134
What are the two available types of estrogen-progestogen therapy regimens?
* Continuous-cyclic (sequential)
* Continuous-combined
* Intermittent-combined (pulsed-progestogen; continuous pulsed)
## Footnote
The continuous-combined regimen is the predominant regimen used in North America.
135
What is the dosing schedule for Continuous-cyclic (sequential) regimen?
* Estrogen: Daily
* Progestogen: 12-14 days per month
## Footnote
This regimen is designed to mimic the natural cycle.
136
What is the dosing schedule for Continuous-combined regimen?
Daily for both estrogen and progestogen
## Footnote
It is used continuously without breaks.
137
What is the dosing schedule for Intermittent-combined regimen?
Daily for estrogen and progestogen, with 14 days every 2-6 months
## Footnote
This regimen allows for breaks in hormone therapy.
138
What are the risks associated with improperly formulated or dosed estrogen plus MP combinations?
Increased risk of endometrial hyperplasia
## Footnote
Micronized progesterone needs to be adequately dosed for endometrial protection.
139
What is the primary concern when assessing endometrial cancer risk?
Adequate dosing of micronized progesterone
## Footnote
Proper dosing is critical to minimize risks.
140
What is intermittent-combined estrogen progestogen therapy?
A regimen that uses estrogen daily with progestogen administered in cycles of 3 days on and 3 days off
## Footnote
This regimen aims to lower uterine bleeding incidence and avoid PR downregulation.
141
What is the clinical goal of progestogen in estrogen-progestogen therapy (EPT)?
To provide endometrial protection while maintaining estrogen benefits and minimizing unwanted progestogen-induced effects
## Footnote
Research is insufficient to recommend one regimen over another.
142
What was the risk of endometrial hyperplasia in women using unopposed estrogen therapy (ET) compared to those using EPT?
34% risk for unopposed ET versus 1% risk for EPT
## Footnote
Data from the PEPI trial showed these results.
143
What does continuous-combined EPT indicate regarding endometrial cancer risk?
No increased risk and may suggest some added protection against endometrial cancer
## Footnote
A cohort study in Finland showed a 76% reduction in endometrial cancer risk with continuous-combined EPT.
144
What are the two types of bleeding commonly seen with hormone therapy?
Withdrawal uterine bleeding and breakthrough uterine bleeding
## Footnote
Withdrawal bleeding occurs after progestogen cessation, while breakthrough bleeding is irregular bleeding during continuous progestogen use.
145
What factors influence the probability of achieving amenorrhea in women using EPT?
Timing of EPT initiation in relation to menopause
## Footnote
Starting EPT 12 months or more after menopause increases the chance of amenorrhea.
146
Which types of progestogen are associated with less breakthrough uterine bleeding?
19-nortestosterone derivatives (norethindrone, NETA, LNG, norgestrel) and oral medroxyprogesterone
## Footnote
These tend to produce less breakthrough bleeding during initial months of use.
147
What effects do progestogens have on other organ systems?
Effects vary depending on progestogen type, dose, route of administration, and EPT regimen
## Footnote
Progestogens can influence factors like thrombotic risk in women with diabetes.
148
What is the relationship between progestogen and breast cancer risk?
Breast cancer risk is not decreased with progestogen addition and may increase with standard doses, particularly synthetic progestins
## Footnote
Some studies suggest no elevated risk with natural progestogen like micronized progesterone.
149
What is the FDA-approved medication that combines a selective estrogen receptor modulator with conjugated equine estrogens?
Duavee (bazedoxifene + CEE)
## Footnote
It is used for treating moderate to severe VMS and for osteoporosis prevention in postmenopausal women.
150
What warnings are included in the boxed warning of all systemic ET and EPT products?
Increased risk of endometrial cancer, stroke, and deep vein thrombosis
## Footnote
The WHI study indicated increased risks associated with these therapies.
151
What common adverse events are associated with estrogen therapy (ET) and estrogen-progestogen therapy (EPT)?
Uterine bleeding, fluid retention, abdominal bloating, gastrointestinal irritation
## Footnote
These AEs can negatively affect quality of life and lead to therapy discontinuation.
152
What is the effect of ultra-low-dose EPT on bleeding?
Bleeding is a less common adverse event
## Footnote
This includes doses like CE 0.30 mg-0.45 mg.
153
What is a common adverse event (AE) associated with estrogen-progestogen therapy (EPT)?
Fluid retention in the hands and feet or abdominal bloating
## Footnote
Other AEs include gastrointestinal irritation and nausea.
154
What were the findings of the Nurses’ Health Study regarding hormone therapy (HT)?
The risk of gastroesophageal reflux symptoms significantly increased with increasing dose and length of exposure to HT.
155
What is the most common AE of transdermal-patch estrogen therapy (ET) or EPT?
Skin irritation at the patch application site.
156
What strategies can alleviate skin irritation from transdermal patches?
Rotate the patch, apply it to the buttock, ensure cleanliness, use OTC hydrocortisone cream, or switch to a different patch with a less irritating adhesive.
157
What are some reported AEs of the vaginal estrogen ring?
Headache, abdominal pain, vaginal pain, irritation, and erosion.
158
True or False: Estrogen vaginal creams can be used as a lubricant during intercourse.
False.
159
What should women be advised regarding the timing of hormone therapy initiation?
It is important to initiate HT closer to the time of menopause for better outcomes.
160
What did the WHI study reveal about the risk of coronary heart disease (CHD) related to timing of HT?
Younger, recently postmenopausal women had a lower absolute risk of CHD compared to older women.
161
What is the timing hypothesis regarding HT use?
There may be less risk and potential CHD benefit when HT is initiated closer to menopause.
162
What adverse events are associated with estrogen therapy (ET) or EPT?
Uterine bleeding, breast tenderness, nausea, abdominal bloating, fluid retention, headache, dizziness, angioedema, mood changes, gallstones, and pancreatitis.
163
What is recommended for women with premature menopause regarding HT?
They can be considered for HT until the average age of menopause to prevent health consequences.
164
What did observational studies show about the effects of ET on atherosclerosis and CVD?
ET has beneficial effects on atherosclerosis, vasodilation, plasma lipids, arterial response to injury, and insulin sensitivity.
165
What is the effect of adding progestogens to estrogen therapy?
It may diminish the beneficial effects of estrogen but does not eliminate them.
166
What is the risk of stroke associated with HT in women aged younger than 60 years?
No increased risk of stroke was found in women who began HT younger than 60 years or within 10 years of menopause.
167
What should be considered when prescribing hormone therapy?
Individual health characteristics, treatment goals, and risks should be assessed.
168
What is the recommended duration for the use of hormone therapy?
The lowest effective dose for the shortest period of time, tailored to the individual.
169
Fill in the blank: The _______ is a clinical trial that showed no increased cardiovascular disease surrogate markers when HT was started closer to menopause.
Kronos Early Estrogen Prevention Study.
170
What is the recommendation for women considering custom compounded hormone therapy products?
They need to be informed of the risks.
171
What is the primary goal of hormone therapy in menopausal women?
To relieve menopause symptoms and prevent bone loss.
172
What should providers determine regarding hormone therapy (HT) for women?
The appropriate type, dose, formulation, route of administration, and duration of therapy based on individual health characteristics and treatment goals.
173
Who can be considered for hormone therapy until the average age of menopause?
Women with premature or early menopause (natural, induced, or surgical).
174
What has numerous clinical trials shown about hormone therapy?
It is effective in preventing osteoporosis and reducing the risk of fractures.
175
What is recommended for women with persistent hot flashes who want to continue treatment?
Very-low doses of hormone therapy for longer-term use to relieve menopause symptoms, prevent bone loss, or improve quality of life (QOL).
176
What is low-dose vaginal estrogen used for?
To relieve progressive symptoms of genitourinary syndrome of menopause (GSM) with minimal risk.
177
What is the most effective treatment for vasomotor symptoms (VMS) and GSM?
Hormone therapy.
178
What factors influence the risks of hormone therapy?
Type, dose, duration of use, route of administration, timing of initiation, and need for progestogen.
179
What is the benefit-risk ratio for women younger than 60 years or within 10 years of menopause onset?
It appears favorable for treatment of bothersome VMS and for those at elevated risk of bone loss or fracture.
180
For women who initiate hormone therapy after 10 or 20 years from menopause onset, what is the benefit-risk ratio?
It appears less favorable than for younger women due to greater absolute risks of CHD, stroke, VTE, and dementia.
181
What does clinical monitoring of women using hormone therapy include?
Ongoing evaluation for potential adverse events (AEs) and periodic reevaluation of the therapy.
182
What is recommended for women to ensure safety while on hormone therapy?
Annual mammography.
183
What should be done if a decision is made to discontinue systemic hormone therapy?
Consideration of abrupt cessation versus tapering the dose.
184
What percentage of women experience a recurrence of symptoms when hormone therapy is discontinued?
Approximately 50%.
185
What is low-dose vaginal estrogen recommended for?
Postmenopausal women whose only menopause symptom is vulvar and vaginal atrophy (VVA).
186
What does bioidentical hormone therapy mean?
Hormones that are chemically identical to those produced by women during their reproductive years.
187
What are custom-compounded hormone drugs?
Hormones crafted for a particular patient by a compounding pharmacy.
188
What is the FDA's stance on the term bioidentical hormone replacement therapy?
It is a marketing term not recognized by the FDA.
189
What are some examples of hormones produced by a woman's body?
* 17β-estradiol
* Estrone
* Estriol
* Progesterone
* Testosterone
190
What is a key concern regarding custom-compounded hormone therapy?
It has not undergone rigorous testing and quality control required for FDA approval.
191
What do topical progesterone products not achieve?
Adequate serum levels to counter the stimulatory effect of estrogen therapy on the uterus.
192
What is the risk associated with some progestogens?
They may increase the risk of breast cancer.
193
What is the purpose of the FDA's agreement with various academic institutions regarding compounded drugs?
To conduct research to inform the public and the agency's policies regarding compounded drugs.
194
What is a common misconception about estriol as an estrogen product?
That it provides benefits without increasing the risk of breast or endometrial cancer.
195
What does the FDA indicate about drug products containing estriol?
They can be compounded in accordance with Section 503A by a licensed pharmacist pursuant to a patient-specific prescription.
## Footnote
This is based on estriol being the subject of an applicable USP monograph.
196
Why did compounding become more popular after the WHI findings?
Symptomatic women had concerns about pharmaceutical-grade HT and believed bioidentical compounded HT products were safer and more effective.
## Footnote
However, these compounded products had not been tested for effectiveness and safety.
197
What is a significant risk associated with compounded products?
They have not undergone premarket review for safety, efficacy, and certain manufacturing controls.
198
Which act clarified the FDA's role in compounded drugs?
H.R.3204 Drug Quality and Security Act.
199
What is the purpose of the FDA’s Compounding Policy Priorities Plan?
To address quality standards for outsourcing facilities and regulate compounding from bulk drug substances.
200
True or False: The benefits and risks of compounded bioidentical HT are considered different from FDA-approved counterparts.
False.
201
What are Selective Estrogen Receptor Modulators (SERMs)?
Compounds that can exhibit both agonist and antagonist properties at estrogen receptors depending on the target tissue.
202
What is the ideal characteristic of a SERM for menopausal women?
Estrogenic action in bone and brain tissue, antiestrogenic effects in other tissues.
203
What types of compounds are classified as naturally occurring SERMs?
Phytoestrogens and xenoestrogens.
204
List the current classes of synthetic SERMs.
* Triphenylethylene (e.g., tamoxifen, toremifene)
* Benzothiophene (e.g., raloxifene)
* Indole derivative (e.g., BZA)
205
What condition was tamoxifen originally approved to treat?
Adjuvant treatment of ER-positive breast cancer.
206
What is the reported risk reduction of invasive ER-positive breast cancer with tamoxifen?
49% in high-risk women.
207
What adverse events are associated with tamoxifen?
* Increased risk of endometrial polyps and cancer
* Increased risk for VTE and pulmonary embolism.
208
What is raloxifene primarily used to treat?
Osteoporosis.
209
What was the outcome of the MORE trial for raloxifene?
Increased BMD in the spine and reduced the risk of vertebral fractures.
210
What was the impact of raloxifene on invasive breast cancer risk in the MORE trial?
Reduced by 76% after 3 years.
211
What was shown in the study comparing tamoxifen and raloxifene for breast cancer prevention?
Both reduced the risk of breast cancer by approximately 50%.
212
What is Bazedoxifene's classification and its use?
Third-generation SERM developed to treat osteoporosis.
213
What is the FDA-approved use of ospemifene?
Treatment of moderate to severe dyspareunia.
214
What kind of warning does ospemifene's labeling contain?
Black box warning regarding concerns for endometrial stimulation, VTE, and stroke.
215
What is toremifene used to treat?
Advanced estrogen-sensitive breast cancer.
216
How does the risk of endometrial cancer compare between tamoxifen and toremifene?
Toremifene has a lower risk of endometrial cancer compared to tamoxifen.
217
What is toremifene?
A triphenylethylene-derived SERM used to treat advanced estrogen-sensitive breast cancer and as adjuvant treatment for early breast cancer.
218
What is the FDA-approved dosage of toremifene?
60 mg per day.
219
How does toremifene compare to tamoxifen regarding uterine effects?
Toremifene demonstrates a weaker effect on the uterine compartment, resulting in a lower risk of endometrial cancer.
220
What is the risk of VTE associated with toremifene compared to tamoxifen?
The risk of VTE appears to be lower with toremifene.
221
What warning has the FDA placed on toremifene?
It may prolong the QT interval, potentially leading to ventricular arrhythmia.
222
What are the favorable effects of toremifene?
Favorable effects on bone mineral density (BMD) and lipid profiles similar to tamoxifen.
223
What does TSEC stand for in the context of hormone therapy?
Tissue Selective Estrogen Complex.
224
What is the purpose of combining a SERM with estrogen in TSECs?
To optimize receptor modulation benefits while minimizing withdrawal endometrial bleeding effects.
225
What was the FDA-approved combination for relieving hot flashes and preventing osteoporosis?
20 mg Bazedoxifene (BZA) combined with 0.45 mg Conjugated Equine Estrogens (CEE).
226
What was the result of the SMART 2 trial regarding hot flashes?
BZA/CEE significantly reduced hot flashes by 74% compared to 51% with placebo at week 12.
227
What improvements were observed in the SMART 3 study related to vaginal health?
Increased superficial cells, decreased parabasal cells, reduced vaginal pH, and decreased vaginal dryness.
228
What was the incidence of endometrial hyperplasia in the studies involving BZA/CEE?
Very low incidence (<1%).
229
What is lasofoxifene?
A third-generation SERM developed for the prevention and treatment of osteoporosis.
230
What effect did lasofoxifene have on vertebral and nonvertebral fractures?
Reduced vertebral fractures by 42% and nonvertebral fractures by 24%.
231
What is dyslipidemia?
Elevated levels of total cholesterol, LDL-C, and non-HDL-C, a risk factor for atherosclerotic cardiovascular disease.
232
What is the primary mechanism of action of statins?
Competitive inhibition of HMG-CoA reductase, reducing cholesterol production in the liver.
233
What is the pooled cohort equation used for?
To estimate 10-year ASCVD risk based on traditional risk factors.
234
What is the recommendation for statin therapy in primary prevention according to the USPSTF?
Moderate-intensity statin therapy for adults aged 40 to 75 years with ASCVD risk greater than 10%.
235
What was the result of the Scandinavian Simvastatin Survival Trial?
Simvastatin reduced the risk of death and coronary events compared to placebo.
236
What was the result of the Cholesterol and Recurrent Events Trial regarding women?
Women showed a greater magnitude of benefit from pravastatin therapy in reducing coronary events.
237
What is the primary trial endpoint decreased by 43% in the Cholesterol and Recurrent Events trial?
Coronary death or nonfatal myocardial infarction (MI)
## Footnote
Statistically significant with P=.035
238
What was the percentage reduction in stroke observed in the Cholesterol and Recurrent Events trial?
56%
## Footnote
Statistically significant with P=.07
239
Which sex demonstrated a greater magnitude of benefit from statin therapy in the Cholesterol and Recurrent Events trial?
Women
240
When did the greatest benefit of statin therapy begin according to the treatment curve?
1 year
241
What organization revised their cholesterol management guidelines in November 2018?
ACC/AHA
242
What concept was introduced in the 2013 ACC/AHA cholesterol guidelines?
Pooled cohort equation and ASCVD risk evaluation
243
What is the most powerful strategy for reducing ASCVD risk according to the 2018 guidelines?
Statin therapy
244
What are the two categories of statin therapy intensity mentioned in the guidelines?
High-intensity and moderate-intensity
245
What LDL-C level reduction is expected from high-intensity statin therapy?
More than 50% on average
246
What LDL-C reduction is associated with moderate-intensity statin therapy?
30% to 50%
247
For adults aged 20 to 75 years with severe hypercholesterolemia, what type of statin therapy is recommended?
High-intensity statin therapy
248
What is the recommended statin therapy for adults aged 40 to 75 years with diabetes mellitus?
Moderate-intensity statin therapy
249
What is the ASCVD risk percentage that warrants moderate-intensity statin therapy for secondary prevention in adults aged 40 to 75 years?
Greater than 7.5%
250
What are the three criteria for the USPSTF recommendation for primary prevention using statins?
* Age 40 to 75 years
* Presence of one or more CVD risk factors
* Calculated 10-year risk of a CV event of 10% or greater
251
What did the Heart Outcomes Prevention Evaluation 3 trial find regarding statin use?
Reduced risk in persons at intermediate risk of ASCVD
252
What does the proposed algorithm for statin use in postmenopausal women assess?
Underlying risk category
253
What are the four potential categories in the proposed algorithm for statin use in postmenopausal women?
* Clinical ASCVD risk
* LDL-C level alone
* Age, LDL-C, and presence of DM
* Age, LDL-C without DM
254
What are the most common adverse events (AEs) associated with statin therapy?
* Myalgias (3-5%)
* Myopathy (0.1-0.2%)
* New-onset diabetes mellitus (9-27%)
* Hepatotoxicity (<1%)
255
What are the four clinical presentations of muscle-related AEs described by the National Lipid Association?
* Myalgias
* Myopathy
* Myositis
* Myonecrosis
256
What is myopathy characterized by?
Muscle weakness with or without elevated creatine kinase (CK) levels
257
What is myositis characterized by?
Muscle tenderness due to inflammation with elevated CK levels
258
What is the most serious form of myonecrosis resulting from statin use?
Rhabdomyolysis
259
What is the primary treatment for statin intolerance due to muscle symptoms?
Discontinuation and rechallenge of statin therapy
260
What serious AEs were noted from a cohort study of patients newly prescribed statins?
* Myopathy
* Acute renal failure
* Cataracts
* Esophageal cancer
* Moderate to severe liver dysfunction
261
What is the highest risk of liver dysfunction associated with which statin?
Fluvastatin
262
What is recommended regarding liver enzyme screening before statin therapy?
Only if symptoms occur after statin initiation
263
What risk factors are associated with the development of new-onset diabetes mellitus during statin therapy?
* Central obesity
* Increased waist circumference
* Elevated triglycerides
* Hyperglycemia
* LDL-C associated with metabolic syndrome
264
What was the conclusion regarding the benefits of statin therapy despite the risk of new-onset diabetes mellitus?
The benefits of CVD reduction and mortality outweigh the harms
