MHTs, SERMs, & TSECs

Question 1

Post-menopause is not medically defined until _______ of complete amenorrhea

Answer 1

12 months

Question 2

The primary therapy for menopausal symptoms is _____

Answer 2

Estrogen

Question 3

The primary therapy for menopausal sxs is estrogen. When would you also add progestin?

Answer 3

Women with an intact uterus that are put on estrogen MUST also be on a progestin d/t increased risk of endometrial hyperplasia/carcinoma from unopposed proliferation

Question 4

Peri-menopause is commonly defined as 2 skipped cycles progressing to 60+ days of amenorrhea. What are treatment options when theses pts have menopausal symptoms but are not yet post-menopausal?

Answer 4

Hormonal contraceptives — provide hormone regulation to reduce symptoms while also providing pregnancy protection

Question 5

Estrogenic forms of menopausal hormone therapy

Answer 5

Estradiol
Conjugated estrogens (CE)
Esterified estrogens (EE)
Estropipate

[all of these have numerous dosage forms available]

Question 6

Progestinic forms of menopausal hormone therapy

Answer 6

Medroxyprogesterone (MPA) — alone or with CE

Methyltestosterone — alone or with EE

Progesterone

Question 7

Estrogen’s cellular MOA

Answer 7

Binds ER in various tissues, transferred into nucleus resulting in increased gene and protein expression leading to physiologic responses

Question 8

Biochemical/physiological effects of estrogen MHT

Answer 8

Decreased production/activity of: Cholesterol, anti-thrombin III, and osteoclast activity

Increased production/activity of: triglycerides and HDL, clotting factors, platelet aggregation, sodium/fluid retention, thyroid binding globulin (TBG)

Question 9

What are the WHI studies?

Answer 9

Examined MHT’s purported beneficial or preventive effects on heart disease, osteoporosis-related fractures, and risk of various cancers (breast, endometrial, colon)

Question 10

Harms vs. benefits found in WHI studies in women taking combined estrogen+progestin MHT

Answer 10

Harms include increased risk of breast cancer, coronary heart disease, dementia, gallbladder disease, stroke, venous thromboembolism, and urinary incontinence

Benefits included better diabetic control, reduced fractures, and reduced colorectal cancers

Question 11

Harms vs. benefits found in WHI studies in women taking estrogen alone for MHT

Answer 11

Harms included increased risk of dementia, gallbladder disease, stroke, venous thromboembolism, and urinary incontinence

Benefits included reduced rates of breast cancer, reduced fractures, and better diabetic control

Question 12

The summary of WHI findings state that MHT very effectively minimizes/treats what 2 symptoms of menopause (and their associated complications)?

Answer 12

Vasomotor symptoms

Vaginal changes

Question 13

T/F: MHT’s benefits on bone and colon cancer risks are outweighed by other risks, and so should not be solely utilized for these purposes

Answer 13

True

[also should not be used to prevent CVD or dementia]

Question 14

What is the recommendation regarding MHT use in younger women?

Answer 14

MHT is an acceptable option for treating moderate to severe menopausal symptoms in relatively young (up to age 59 or within 10 years of menopause) and healthy women

Individualization with risk-stratification is key

Some organizations recommend patch over oral therapy

Question 15

What is the recommendation regarding MHT in women with vaginal symptoms only?

Answer 15

Preferred treatments are low doses of vaginal estrogen (topical)

Question 16

What is the recommendation regarding MHT in women at risk of blood clots/stroke?

Answer 16

Both estrogen-alone therapy and estrogen+progestin therapy increases risk of blood clots

Although risks of blood clots and strokes increase with either type of MHT, risk is less in 50-59 age group

Question 17

When is an increased risk of breast cancer seen in patients on MHT?

Answer 17

Within 3-5 years of continuous estrogen with progestin therapy

Question 18

T/F: risks and benefits of MHT are attenuated/eliminated several years after therapy is stopped

Answer 18

True

Question 19

What is the goal of selective estrogen receptor modulators (SERMs)?

Answer 19

Beneficial pro-estrogenic (agonist) actions in select tissues with beneficial (or non-harmful) anti-estrogenic (antagonist) actions in other tissues

Question 20

What is the goal of tissue selective estrogen complexes?

Answer 20

Combines unique elements of a SERM with an estrogen compound

Question 21

2 major SERMs

Answer 21

Ospemifene

Clomiphene

Question 22

TSEC currently only available as a combo with CE

Answer 22

Bazedoxifene

Question 23

Only indication for SERM ospemifene

Answer 23

Treatment of moderate-to-severe dyspareunia (painful intercourse)

[used if pt doesn’t want topical estrogen]

Question 24

MOA of osepemifene used for dyspareunia

Answer 24

Functions as estrogen agonist by binding to ERs in vagina, but also anti-estrogenic on breast

Increases superficial cell growth (on vaginal smear), increases vaginal secretions, decreases vaginal pH, reduces pain/discomfort during vaginal intercourse

Stimulatory endometrial effects — no known increased risk of endometrial cancer; yet used alone with caution in women with intact uterus

Question 25

Side effects of ospemifene

Answer 25

Worsening of hot flashes/sweating

Estrogenic-similar effects on coagulation (stroke/VTE demonstrated; albeit at a lower rate than estrogens alone)

Endometrial thickening (proliferation) and even hyperplasia (estrogenic agonist)

Question 26

Contraindications to ospemifene

Answer 26

Same as estrogens!

Unusual/abnormal vaginal bleeding

Thromboembolic diseases (exercise caution in smokers)

Estrogen-related neoplasias (uterine, ovarian, breast)

Question 27

Indications for bazedoxifene w/CE

Answer 27

Used in women with intact uterus

Treats moderate-to-severe vasomotor symptoms associated with menopause in women with a uterus

Prevention of post-menopausal osteoporosis (along with calcium and vitamin D)

Question 28

MOA of bazedoxifene w/CE

Answer 28

Antagonistic activity in endometrium (replaces progestin-concept in women with an intact uterus) and in breast tissue; but also estrogenic (agonist) physiological effects, especially in bone (CE agent)

Less vaginal bleeding than CE w/ progestin therapy

Question 29

How is bazedoxifine (2nd gen) different from 1st gen SERMs?

Answer 29

Bazedoxifene does not stimulate endometrial proliferation

Has been shown to destroy HER2 malignant cells (SERDs), including cells resistant to Tamoxifen, similar to anti-estrogen drug Fulvestrant

Question 30

Side effects of Bazedoxifene

Answer 30

All estrogen-related effects (due to CE component)

Bazedoxifene-specific = has the potential of worsening hot flashes/sweating (similar to Tamoxifen, Raloxifene, and ospemifene)

Contraindicated in all situations estrogens are due to CE component

Question 31

Example of anti-estrogen medication indicated in cases of infertility in anovulatory women

Answer 31

Clomiphene

Question 32

MOA of clomiphene

Answer 32

Most significant effect on induction of oculation in women with amenorrhea, PCOS, and dysfunctional bleeding with anovulatory cycles

Primarily blocks inhibitory actions of estrogen on hypothalamus GnRH and pituitary gonadotropin release

Question 33

Side effects of Clomiphene

Answer 33

Multiple births (3-5% increase; 99% twins)

Ovarian cysts (ovarian cancer possible with prolonged use, so many clinicians limit use to 3 cycles)

Hot flashes

Luteal phase dysfunction (inadequate progesterone production)