Podcast Beta
Questions and Answers
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?
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?
Signup and view all the answers
Which benefit of hormone replacement therapy is evidenced by its efficacy in menopausal women?
Signup and view all the answers
What is the primary mechanism by which SSRIs help reduce hot flashes?
Signup and view all the answers
Which SSRI is specifically FDA-approved for treating vasomotor symptoms in postmenopausal women?
Signup and view all the answers
How much can SSRIs reduce the frequency and intensity of hot flashes?
Signup and view all the answers
What common side effect is associated with SNRIs?
Signup and view all the answers
What condition might lead a woman to choose SSRIs or SNRIs over Hormone Replacement Therapy (HRT)?
Signup and view all the answers
Which SNRI is most commonly used for treating hot flashes?
Signup and view all the answers
What neurotransmitter does SNRIs primarily increase alongside serotonin?
Signup and view all the answers
What is a potential side effect of SNRIs when taken at higher doses?
Signup and view all the answers
What is considered premature menopause?
Signup and view all the answers
Which of the following genetic factors can increase the risk of premature menopause?
Signup and view all the answers
Which autoimmune disease is NOT linked to premature menopause?
Signup and view all the answers
What medical treatment is associated with the risk of premature menopause?
Signup and view all the answers
What is the impact of oophorectomy on menopause?
Signup and view all the answers
Which of the following is considered a typical symptom of premature menopause?
Signup and view all the answers
Which factor is NOT typically associated with premature ovarian insufficiency?
Signup and view all the answers
What role does family history play in premature menopause?
Signup and view all the answers
What is one benefit of adding progesterone in hormonal therapy?
Signup and view all the answers
Which regimen would be preferred for elderly females in hormonal therapy?
Signup and view all the answers
What is the active ingredient in Conjugated Equine Estrogens (CEEs)?
Signup and view all the answers
Which component primarily affects the metabolism of estrogens in the body?
Signup and view all the answers
What is the role of progestogens in hormonal therapy?
Signup and view all the answers
What is one reason for using synthetic preparations of estrogen?
Signup and view all the answers
Which delivery method is preferred for 17-beta estradiol due to its poor oral absorption?
Signup and view all the answers
Which dosage is equivalent to 1 mg micronized 17-beta estradiol?
Signup and view all the answers
What are progestins primarily classified based on?
Signup and view all the answers
Which of the following is a structural derivative of testosterone?
Signup and view all the answers
What is the main purpose of gonanes?
Signup and view all the answers
Which of the following is NOT part of the sequential combined HRT preparations?
Signup and view all the answers
How does oral progesterone primarily undergo metabolism?
Signup and view all the answers
What is the approximate half-life of norethindrone?
Signup and view all the answers
Which adverse effect is commonly associated with the use of progestins?
Signup and view all the answers
Which progestin is recommended to be used separately for sequential therapy?
Signup and view all the answers
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.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
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.
