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Hormone replacement therapy
Lecture 21
24
Pharmacology
Professional
10/11/2012

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Term
What is the definition of menopause?
Definition
- Final menstrual period confirmed 12 months after amenorrhea. Reduced functioning of the ovaries, no ovulation
- Can be induced surgically.
**peri-menopause - menopausal tranition, an indication that ovarian function is declining. Variable cycle length and skipped cycles.
Term
When does menopause happen and what affects this?
Definition
- Median onset between 50 and 52. Genetics play a role.
- Factors for early onset: smoking, fiber, low BMI
**low BMI - less estrogen due to less aromatase.
Term
What anatomical changes take place in menopause?
Definition
Ovarian depletion - depletion of follicles.
Endometrial atrophy and mammary gland no longer secretory.
Term
What hormonal changes take place in menopause?
Definition
- Estrogen increase then sharp decrease (estradiol). Estrone becomes dominant estrogen.
- Decrease in inhibin and compensatory effect in gonadotropins: Increased LH and greatly increase FSH.
Term
What estrogen is the most potent?
Which is most prevalent post-menopause?
Definition
- Estradiol - most potent, prevalent pre-menopause
- Estrone - converted from aromatase, higher post-menopause.
Term
What are the menopausal changes is progesterone and androgens?
Definition
- Progesterone - levels undetectable, no corpus luteum
- Androgens - Testosterone levels similar, much lower levels of androstendione.
Term
What are vasomotor symptoms?
Definition
Hot flashes! Due to peak in estrogen --> low estrogen causes estrogen withdrawal. Transient, can last ~5 years.
Start to increase peri-menopause, most prominent in late menopausal transition
Term
What are the other clinical presentations of menopause?
Definition
- Vaginal atrophy - persists or worsens with aging. Incontinence and infection
- Dysfunctional uterine bleeding - due to estrogen unopposed by progesterone. Hyperplasia can lead to cancer. High BMI makes this worse.
- Decreased BMD
- Sexual dysfunction - due to low androgen lvls
- Mood and sleeping difficulty - due to life changes
- Weight gain
Term
What are common presenting signs of menopausal transition?
First line?
Definition
Dysfunctional uterine bleeding, uterine fibroids, endometrial hyperplasia.
- First line - oral contraceptives. Either monophasic or progestin-only
Term
What are the indications for oral estrogen replacement?
Definition
- Relief of vasomotor symptoms - The gold standard. Use a low dose for a short duration.
- Tx of vaginal atroph
- Prevention of osteoporosis - secondary to bisphosphonates
Term
What products are used for estrogen replacement therapy?
Definition
- Premarin
- Synthetic conjugated estrogens: Cenestin (type A), Enjuvia (type B)
- Menest - esterified estrogen
- Estradiol - Femtrace/Estrace/Gynodiol
- Estropipate
Term
How does oral estrogen work for menopause?
Definition
- Increases SHBG = decrease in androgens --> reduced libido.
AE: GI, breakthrough bleeding, breast tenderness, edema. Titration to manage symptoms
Term
What are the benefits of topical estrogens?
Definition
Avoid first pass metabolism --> better lipid profile, less clotting factors. Less CRP
Term
What are combination products for menopause Tx?
Definition
- CEE + progestin (Prempro, premphase)
- Estradiol + Progestin (Angeliq, Femhrt, Activella)
- Esterified estrogens + methyltestosterone
- Combipatch or ClimaraPro
**Helps with libido
Term
How is urogenital atrophy treated in menopause?
Definition
Vaginal estrogen is preferred:
- Premarin cream
- Estrace cream
- Estradiol ring - Estring or Femring
- Vagifem
Term
How can estrogen be used for osteoporosis?
Definition
Prevention, not Tx. Both oral and transdermal products, reducing the risk of a fracture.
Term
What is endometrial hyperplasia?
Definition
Growth of the endometrial wall caused by unopposed estrogen/no progesterone in menopause. Can lead to cancer
- Presentation - irregular bleeding.
- PEPI trial - CEE alone causes significantly more hyperplasia than combo products.
Term
When do you use progesterone therapy in menopausal women?
Definition
When the woman has an INTACT uterus - prevention of endometrial hyperplasia.
Unnecessary in hysterectomy. Do not have to use w/ vaginal estrogen.
**withdrawal of progesterone = bleeding
Term
What progesterone product requires monitoring?
Definition
drospirenone - an aldosterone antagonist. Monitor K and SCr, do not give to patients w/ poor renal fxn.
Term
How does estrogen affect the CV system?
Definition
The E2 receptor is on BVs --> increased NO, decreased constriction, and decreased LDL.
Term
What is the HERS trial?
Definition
A study done in post-menopausal women to evaluate estrogen effects on CURRENT CHD. Established coronary disease.
**No significant benefit of using estrogen.
Term
What is the WHI trial?
Definition
Study on postmenopausal women (~63) for primary prevention of CHD and breast cancer
- no effect on CHD
- may actually increase risk of breast cancer
** risks of therapy may outweigh benefit.
Term
In the WHI trial, how do age groups compare?
Definition
- Ages 70-79 have a positive risk for CHD on CEE + MPA
- Directly after menopause, therapy is ok. 20 years after menopause, therapy causes CHD
** Longer use = increased risk --> Timing hypothesis
Term
What is the gap hypothesis in menopause?
Definition
In breast cancer, early use in menopause INCREASES risk. In later years, no significant risk
** Use low dose for short duration.
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