Menopause & Hormonal Replacement Therapy Flashcards
What is is Menopause?
Menopause is the permanent cessation of menses.
How is Menopause determined?
- 12 consecutive months of amenorrhea.
- Physiologically, it is the cessation of ovarian follicular activity.
- Ovulation, estrogen & progesterone secretion
What is the median age of onset of Menopause?
51
2 yrs earlier than average if hysterectomy.
49 in smokers
What happens in conjunction w/ menopause?
- Follicular Depletion
- born with 2 million ovulate but ovulate
What happens to the level of circulating androgens as menopause approaches?
Levels fall.
What do Post-menopausal ovaries secrete? And why?
- Primarily androgens.
- accounts for 50% of circulating androgens.
- Adrenals and peripheral tissue synthesize rest. - Elevated LH levels at menopause.
What is Perimenopause?
The period preceding (2-4yrs) and the year following menopause.
What happens during Perimenopause?
- Menstrual cycle irregularity, anovulatory cycles.
- Vasomotor symptoms
- Psychological symptoms
- Sleep Disturbances
- Sexual issues
- 10-15 fold increase in FSH, 4-5 fold increase in LH, 90% decrease in estradiol.
What was the Women’s Health Initiative (WHI)?
- Set of clinical trials and studies to address health issues in post-menopausal women.
What were the 3 interventions used in the WHI?
- Hormone Therapy
- Dietary Modification
- Calcium/Vit D supplementation.
Characteristics of Hormonal therapy in WHI?
- conjugated equine estrogen + MPA
-Hysterectomy CEE only. - Expected to decrease CHD
-Increased stroke - Expected to increase risk of breast cancer.
-combination EandP did
halted 5 years in
Characteristics of Dietary Modification in WHI?
- Low fat diet
- Expected to decrease CHD, stroke, CVD
- modest decrease - Expected to decrease risk of colorectal cancer.
- possible - Expected to decrease risk of breast cancer.
- dont know
Characteristics of Calcium/Vit D supplementation in WHI?
- 1g/d Ca, 400 IU of Vit D
- Expected to reduce risk of bone fractures.
- Expected to reduce risk of colorectal can
- NO - Increased risk of kidney stones.
Criticisms of WHI?
- Low adherence, High attrition
- Under reported benefits
- Ave age was 63, menopause typically begins 51.
- Only 3.5% age 50-54
What are the goals of treatment for menopause?
- Relieve menopausal symptoms
- hot flashes (short term) - Prevention of osteoporosis (long term)
- balance against risks - Estrogen + Progestogen is recommended therapy.
- Estrogen only if hysterectomy
- Progestogen protects against uterine/endometrial cancer.
What oral estrogens are used to treat Menopausal symptoms?
- Conjugated Equine Estrogens
- 50-60% estrone sulfate, remainder equine
- std. dose = 0.625mg/d - Oral Estradiol (Estrace, micronized estradiol)
- Estradiols converted to estrones in intestinal mucosa and liver.
Increase hepatic synthesis SHBG
What are characteristics of Transdermal Estrogens?
- Bypass liver/GI, first-pass metabolism
- more physiological estradiol/estrone ratio
- DONT increase SHBG, lower lipids
- once or twice wk 50ug/d equals .625mg CEE.
- Gels and creams less consistent.
What are characteristics of SQ implants of estrogen?
Can last up to a year.
NOT popular in US.
What are characteristics of intranasal spray estrogens?
once/twice daily
as effective as oral or transdermal.
Characteristics of Vaginal rings?
Estring, Femring
1. Effective at low doses, lower serum lipids and decrease bone loss.
Last for 3 months
What are AE of estrogens?
Nausea, HA, breast tenderness, heavy bleeding.
Long term:
-Thromboembolism, CHD, stroke, breast cancer.
Drug Drug interactions of estrogens?
- Anticonvulsive may increase estrogen metabolism. Higher doses needed.
- Estrogens increase TBG, CBG
What are Phytoestrogens?
Soy Isoflavones, popular but not effective.
Why are Progestogens always included in HRT?
To suppress endometrial hyperplasia/cancer.
NOT in women w/ hysterectomy
