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Questions and Answers
What is the primary benefit of initiating hormone replacement therapy (HRT) early after menopause?
What is the primary benefit of initiating hormone replacement therapy (HRT) early after menopause?
Which of the following hormone therapy formulations is associated with a higher risk of breast cancer when initiated shortly after menopause?
Which of the following hormone therapy formulations is associated with a higher risk of breast cancer when initiated shortly after menopause?
What is the effect of oral hormone formulations on venous thromboembolism risk?
What is the effect of oral hormone formulations on venous thromboembolism risk?
How does the duration of estrogen plus progesterone therapy affect endometrial cancer risk?
How does the duration of estrogen plus progesterone therapy affect endometrial cancer risk?
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Which benefit of hormone replacement therapy is evidenced by its efficacy in menopausal women?
Which benefit of hormone replacement therapy is evidenced by its efficacy in menopausal women?
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What is the primary mechanism by which SSRIs help reduce hot flashes?
What is the primary mechanism by which SSRIs help reduce hot flashes?
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Which SSRI is specifically FDA-approved for treating vasomotor symptoms in postmenopausal women?
Which SSRI is specifically FDA-approved for treating vasomotor symptoms in postmenopausal women?
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How much can SSRIs reduce the frequency and intensity of hot flashes?
How much can SSRIs reduce the frequency and intensity of hot flashes?
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What common side effect is associated with SNRIs?
What common side effect is associated with SNRIs?
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What condition might lead a woman to choose SSRIs or SNRIs over Hormone Replacement Therapy (HRT)?
What condition might lead a woman to choose SSRIs or SNRIs over Hormone Replacement Therapy (HRT)?
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Which SNRI is most commonly used for treating hot flashes?
Which SNRI is most commonly used for treating hot flashes?
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What neurotransmitter does SNRIs primarily increase alongside serotonin?
What neurotransmitter does SNRIs primarily increase alongside serotonin?
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What is a potential side effect of SNRIs when taken at higher doses?
What is a potential side effect of SNRIs when taken at higher doses?
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What is considered premature menopause?
What is considered premature menopause?
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Which of the following genetic factors can increase the risk of premature menopause?
Which of the following genetic factors can increase the risk of premature menopause?
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Which autoimmune disease is NOT linked to premature menopause?
Which autoimmune disease is NOT linked to premature menopause?
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What medical treatment is associated with the risk of premature menopause?
What medical treatment is associated with the risk of premature menopause?
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What is the impact of oophorectomy on menopause?
What is the impact of oophorectomy on menopause?
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Which of the following is considered a typical symptom of premature menopause?
Which of the following is considered a typical symptom of premature menopause?
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Which factor is NOT typically associated with premature ovarian insufficiency?
Which factor is NOT typically associated with premature ovarian insufficiency?
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What role does family history play in premature menopause?
What role does family history play in premature menopause?
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What is one benefit of adding progesterone in hormonal therapy?
What is one benefit of adding progesterone in hormonal therapy?
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Which regimen would be preferred for elderly females in hormonal therapy?
Which regimen would be preferred for elderly females in hormonal therapy?
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What is the active ingredient in Conjugated Equine Estrogens (CEEs)?
What is the active ingredient in Conjugated Equine Estrogens (CEEs)?
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Which component primarily affects the metabolism of estrogens in the body?
Which component primarily affects the metabolism of estrogens in the body?
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What is the role of progestogens in hormonal therapy?
What is the role of progestogens in hormonal therapy?
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What is one reason for using synthetic preparations of estrogen?
What is one reason for using synthetic preparations of estrogen?
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Which delivery method is preferred for 17-beta estradiol due to its poor oral absorption?
Which delivery method is preferred for 17-beta estradiol due to its poor oral absorption?
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Which dosage is equivalent to 1 mg micronized 17-beta estradiol?
Which dosage is equivalent to 1 mg micronized 17-beta estradiol?
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What are progestins primarily classified based on?
What are progestins primarily classified based on?
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Which of the following is a structural derivative of testosterone?
Which of the following is a structural derivative of testosterone?
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What is the main purpose of gonanes?
What is the main purpose of gonanes?
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Which of the following is NOT part of the sequential combined HRT preparations?
Which of the following is NOT part of the sequential combined HRT preparations?
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How does oral progesterone primarily undergo metabolism?
How does oral progesterone primarily undergo metabolism?
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What is the approximate half-life of norethindrone?
What is the approximate half-life of norethindrone?
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Which adverse effect is commonly associated with the use of progestins?
Which adverse effect is commonly associated with the use of progestins?
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Which progestin is recommended to be used separately for sequential therapy?
Which progestin is recommended to be used separately for sequential therapy?
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Study Notes
Premature Menopause
- Occurs when ovaries stop functioning before age 40.
- Leads to estrogen drop and early menopausal symptoms.
- Causes:
-
Genetic Factors:
- Family history of early menopause increases risk.
- Turner syndrome (missing or incomplete X chromosome) leads to ovarian dysfunction.
- Fragile X syndrome carriers have a higher risk of premature menopause.
-
Autoimmune Diseases:
- Immune system attacks ovaries, causing ovarian failure.
- Diseases include:
- Thyroid disorders (Hashimoto's thyroiditis)
- Rheumatoid arthritis
- Addison's disease
- Type 1 diabetes
-
Medical Treatments:
- Chemotherapy and radiation therapy can damage ovaries.
- Surgical removal of ovaries (oophorectomy) causes immediate menopause.
- Pelvic surgery can inadvertently damage ovaries.
-
Natural Aging:
- Can be a factor, but premature menopause occurs before age 40.
-
Genetic Factors:
Hormone Replacement Therapy (HRT)
-
Types:
-
Combined E+P: Estrogen and Progesterone
- For hysterectomized women.
- Benefits: Relieves menopausal symptoms and prevents endometrial cancer.
- Forms: Oral tablets, patches, combined regimens.
-
Estrogen only:
- For women with a uterus.
- Prevents endometrial overgrowth.
- Can be administered sequentially or continuously.
- Sequential Regimen: Alternates estrogen and estrogen-progestin, causing withdrawal bleeding.
- Continuous Regimen: Preferred for elderly women who don't need monthly bleeding.
-
Combined E+P: Estrogen and Progesterone
-
Estrogen Preparations:
- 17-beta estradiol: Poor oral absorption, used in parenteral formulations.
- Micronized 17-beta estradiol: Bioidentical to premenopausal ovary product.
- Conjugated equine estrogens (CEEs): Derived from mare urine.
- Esterified estrogen:
- Ethynyl Estradiol: Most potent estrogen, used in low doses in HRT.
- Efficacy is similar across preparations.
-
Estrogen Dosage Equivalents:
- 0.625mg Conjugated equine estrogen
- 1 mg micronized 17-beta estradiol
- 0.05 mg/day transdermal 17-beta estradiol
- 1.25 mg piperazine estrone sulfate
- Estradiol gels and sprays are available in various strengths.
-
Estrogen Mechanism of Action:
- Oral
- Spray
- Patch
- Vaginal ring
- Gel
-
Drug-Drug Interactions:
- Estrogens metabolized by CYP3A enzymes.
- CYP3A inhibitors increase estrogen levels.
- CYP3A inducers decrease estrogen levels.
- Increases TBG (thyroid-binding globulin), affecting T4 levels.
-
Progestogen Preparations:
- Progesterone: Naturally occurring hormone.
- Progestogen: Synthetic or natural molecule with similar effects to progesterone.
- Progestins: Synthetic progestogens.
-
Structural Classification:
- Pregnanes: Medroxyprogesterone acetate, Nomegestrol acetate
- Estranes: Norethindrone, norethindrone acetate, ethynodiol diacetate, norethynodrel
- Gonanes: Levonorgestrel, desogestrel, Norgestimate, Gestodene
-
Generational Classification:
- Progestogens classified based on generations of development.
Progestogen Preparations for HRT
- Various progestogens used in HRT, each with different properties and side effect profiles.
Combined HRT Preparations
-
Sequential Combined Formulations:
- 1-2 mg oestradiol + 10mg dydrogesterone (Elleste, Femoston)
- 1-2 mg oestradiol + 1mg norethisterone acetate
- 1-2mg oestradiol + 1 mg norethisterone acetate
-
Sequential Therapy: Estrogen and Progesterone Taken Separately
- Oral oestradiol 1 -2 mg
- Micronised progesterone (taken separately):
- Utrogestan 200mg orally for 12 days
- Provera 10mg orally for 12 days
- Norethisterone 5mg orally for 12 days
- Mirena intrauterine system
-
Continuous Combined HRT:
- 1-2 mg oestradiol + 100 mg progesterone (Femoston conti)
- 1-2 mg oestradiol + 5mg dydrogesterone
- 1-2 mg oestradiol + 0.5mg norethisterone acetate
- 1-2 mg oestradiol + 2.5mg medroxyprogesterone acetate
- 1-2 mg oestradiol + 5mg medroxyprogesterone acetate
-
Estrogen and Progesterone can be taken separately with low dose of Progesterone.
Metabolism and Pharmacokinetics
- Oral progesterone: Undergoes hepatic first-pass metabolism.
- Plasma protein binding: Free or bound to albumin or other transport proteins.
- Bioavailability: Increased when micronized.
- Oral: Peak serum concentrations within 1-3 hours.
- Half-life: Varies based on progestogen type.
Adverse Effects
- Fluid retention
- Bloating
- Breast tenderness
- Headaches
- Mood changes
- Nausea
- Lowering dose or switching to different estrogen/progestogen can alleviate side effects.
Benefits vs Risk of HRT
-
Cardiovascular Health:
- Estrogen promotes vasodilatation, improving metabolic profile.
- Protection from cardiovascular events, especially when used early after menopause.
- Some RCTs (WHI) failed to show benefit in older women.
- "Timing hypothesis": HRT may be beneficial early after menopause, reducing atherosclerosis and cardiovascular events in women under 60 years old, started < 10 years of menopause.
- Blood pressure reduction with drosperinone.
-
Breast Cancer Risk:
- Risk varies based on formulation, timing, duration of HRT.
- Estrogen stimulates breast tissue proliferation.
- WHI showed increased risk with CEE+MPA.
- Transdermal E reduced risk compared to oral E.
- "Gap time hypothesis": Increased breast cancer risk when HRT started less than 5 years after menopause, particularly within 1 year.
-
Endometrial Cancer (EC):
- Women with unbalanced estrogen exposure are at increased risk.
- Sequential E+P regimen showed decreased risk for EC when used < 5 years, increased risk when used longer.
-
Venous Thromboembolism:
- Increased risk with oral formulations due to higher liver concentration.
- Increased production of coagulation and fibrinolysis factors.
-
Bone Health:
- HRT reduces bone loss in menopausal women.
Other Hormone-Sensitive Conditions
- HRT can be used to manage other conditions, like hot flashes, vaginal atrophy, and sleep disturbances.
- Non-hormonal therapies like SSRIs and SNRIs can also be effective for hot flashes.
SSRIs (Selective Serotonin Reuptake Inhibitors)
- Mechanism of Action: Increase serotonin levels, regulating mood and thermoregulation.
-
Common SSRIs for Vasomotor Symptoms:
- Paroxetine (FDA-approved for hot flashes)
- Fluoxetine and Citalopram (off-label use)
- Effectiveness: Reduce hot flash frequency and intensity by 50-60%.
- Side Effects: Nausea, fatigue, sleep disturbances, sexual dysfunction.
SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)
- Mechanism of Action: Increase serotonin and norepinephrine levels, involved in mood regulation and thermoregulation.
-
Common SNRIs for Vasomotor Symptoms:
- Venlafaxine (most common)
- Desvenlafaxine
- Effectiveness: Reduce hot flashes by 40-60%.
- Side Effects: Similar to SSRIs, including nausea, dry mouth, dizziness, increased blood pressure.
When to Use SNRIs/SSRIs
- When HRT is contraindicated due to cancer, cardiovascular disease, or thromboembolic disorders.
- For women who prefer not to use hormones.
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Description
This quiz examines the causes and implications of premature menopause, which occurs when the ovaries stop functioning before age 40. It highlights genetic factors, autoimmune diseases, medical treatments, and the role of natural aging in this condition.
