Hormone Therapy, SERMS

Question 1

Menopausal transition

Answer 1

(referred to as peri-menopause)

• inc in FSH, reduction in H levels, and variation of cycle begins
• commonly seen as 2 skipped cycles progressing to 60 or more days of amenorrhea

Question 2

Post-menopause

Answer 2

• starts with last menstrual period

- not medically defined until 12 months of complete amenorrhea

Question 3

menopause sx’s

Answer 3

• hot flashes
• night sweats
• vaginal dryness, painful intercourse, sexual dysfxn
• sleep disturbances
• mood/cognitive issues
• urinary incontinence
• reduced quality of life

Question 4

Inc in prevalance during menopause

Answer 4

• Bone effects- osteopenia, osteoporosis, fractures

- CV effects- ACS, MI, CVD

Question 5

primary tx for menopausal sx’s

Answer 5

Estrogen!!
-women with an intact uterus must also be on progestin!!! (endometrial hyperplasia and carcinoma due to unopposed prolif for prolonged duration)

Question 6

peri-menopause- tx

Answer 6

• HC tx or MHT

- HC tx- H regulation and pregnancy protection

Question 7

Estrogen therapy- available estrogenic forms

Answer 7

• estradiol
• conjugated estrogens (CE)
• esterified estrogens (EE)
• estropipate

Question 8

Menopausal H therapy- available progestin components

Answer 8

• Medroxyprogesterone (MPA)- MPA alone or with CE
• Methyltestosterone- alone or with EE
• Progesterone- alone

Question 9

Estrogen and Progesterone Effects- cellular moa

Answer 9

-binds to Rs in various tissues, transferred into nucleus, resulting in inc gene and protein expression

Question 10

strogen-only H therapy- effects

Answer 10

-endometrial- proliferation

progestin’s oppose estrogen’s effects

Question 11

Estrogen-only H therapy- effects- dec production/activity of?

Answer 11

• chol
• anti-thrombin III
• osteoclastic activity

Question 12

Estrogen-only H therapy- effects- inc production/activity of?

Answer 12

• triglyceride and HDL-C
• clotting factors
• platelet aggregation
• Na/fluid retention
• thyroid binding globulin

Question 13

Objective of H trials of Women’s Health Initiative Study

Answer 13

-examine MHTs beneficial or preventive effects on Heart disease, osteoporosis-related fractures, and risk of various cancers (breast, endometrial, colon cancers)

Question 14

Women’s Health Initiative Study- findings

Answer 14

• MHT very effectively minimizes/treats vasomotor sx’s and vaginal changes (and their assoc complications)
• MHT should NOT be used to prevent CVD or dementia

Question 15

5 major points of agreement

Answer 15

• for younger women- treat menopausal sx’s (up to 50 yo or within 10 yrs of menopause)
• for women with vaginal sx’s only- low doses of vaginal estrogen (topical)
• for women with a uterus- need to take progestin to prevent uterine cancer
• for women at risk of blood clots/stroke- estrogen and estrogen w/ progestin tx inc risk of blood clots (risk less in 50-59 yo)
• for women at risk of breast cancer- risk seen within 3-5 yrs of continuous estrogen and progestin tx- risk decs after MHT is stopped

Question 16

if therapy needed for moderate-severe vasomotor sx’s

Answer 16

• use lowest dose possible to control sx’s
• treat for shortest duration possible
• revaulate at least yearly for ongoing tx need

Question 17

SERMs- goal?

Answer 17

(Selective Estrogen R Modulators)
-beneficial pro-estrogenic actions in select tissue with beneficial (or non-harmful) anti-estrogenic actions in other tissues- bone, brain, breast, endometrium

Question 18

TSECs- goal?

Answer 18

(Tissue Selective Estrogen Complexes)

-combines the unique elements of a SERM with an estrogen compound

Question 19

SERMs

Answer 19

• OspemIFENE

- BazedoxIFENE

Question 20

SERMs- indications

Answer 20

Ospemifene

-tx of moderate-to-severe dyspareunia- sx of vulvar and vaginal atrophy of menopause

Question 21

Ospemifene (dyspareunia)- moa

Answer 21

• estrogen agonist- binds to ER’s in vagina, also anti-estrogenic on breast
• inc superficial cell growth, inc vaginal secretions, dec vaginal pH, reduce pain/discomfort during sex
• stimulatory endometrial effects- no known inc risk of endometrial cancer

Question 22

Ospemifene (dyspareunia)- Side Effects

Answer 22

• worsening of inc in hot flashes/sweating
• estrogenic-similar effects on coagulation (Stroke/VTE demonstrated; albeit at a lower rate than estrogens alone)
• endometrial thickening (prolif) and even hyperplasia- concern for progression to malignancy, but no cases in clinical trials

Question 23

Ospemifene (dyspareunia)- contraindicated in

Answer 23

(as all estrogens are)

• unusually/abnormal vaginal bleeding
• thromboembolic diseases (CVA, MI, VTE, Pe, DVT, caution in smokers)
• estrogen-related neoplasia- uterine, ovarian, breast

Question 24

TSECs- indications

Answer 24

Bazedoxifene (with CE)- for women with intact uterus

• tx of moderate-to-severe vasomotor sx’s assoc with menopause in women with a UTERUS
• prevention of post-menopausal osteoporosis in women with a uterus

Question 25

Bazedoxifene (with CE)- moa

Answer 25

- antagonistic activity in endometrium (replaces progestin-concept in women with an intact uterus) and in breast tissue - estrogenic physiological effects, esp in bone (due to CE) - diff from 1st gen SERMs- doesnt stim endometrial prolif; destroys HER2 malignant cells - less vaginal bleeding than CE with progestin tx

Question 26

Bazedoxifene (with CE)- SE's

Answer 26

- all estrogen-related effects (due to CE) - Bazedoxifene specific- worsening hot flashes/sweating - contraindicated- in all situations estrogens are (due to CE)