MHT and SERMS

Question 1

What are some symptoms of menopause?

Answer 1

• Hot flashes
• Night sweats
• Vaginal dryness/painful intercourse/sexual dysfunction
• Sleep disturbances
• Mood/cognitive issues
• Urinary incontinence

Question 2

What is the primary therapy for menopausal symptoms?

Answer 2

• Estrogen
• With/without the addition of progestin
• Women with an intact uterus must also be on a progestin

Question 3

Why must a women with a uterus be on a progestin as well as estrogen?

Answer 3

• To reduce the risk of endometrial hyperplasia/carcinoma from unopposed tissue proliferation with prolonged duration

Question 4

What are the four estrogenic forms for menopausal hormone therapy?

Answer 4

• Estradiol: in acetate form (tablet/vaginal ring) and cypionate form (injection
• Conjugated estrogens (CE): blend of 6 known estrogen derivatives
• Esterified estrogens (EE): combination of Na+ estrone sulfate and Na+ equilin sulfate
• Estropipate: crystalline estrone solubilized with sulfate and stabilized with piperazine

Question 5

What are some available progestinic components used for menopausal hormone therapy?

Answer 5

• Medroxyprogesterone
• Methyltestosterone
• Progesterone

Question 6

What is the MOA of estrogen?

Answer 6

• Bind to estrogen receptors in various tissues, transferred into nucleus resulting in increased gene and ultimately protein, expression resulting in physiological responses

Question 7

What are the effects of estrogen?

Answer 7

• It has a proliferative effect which causes there to be a requirement that if a woman still has their uterus, need to give a progestin as well to counteract the estrogen

Question 8

What does estrogen decrease in the body?

Answer 8

• Cholesterol
• Anti-thrombin III
• Osteoclastic activity (bone turnover)

Question 9

What does estrogen increase in the body?

Answer 9

• Triglycerides and HDL-C
• Clotting factor
• Platelet aggregation
• Sodium/fluid retention
• Thyroid binding globulin (TBG)

Question 10

What was the objective of the women’s health initiative study?

Answer 10

• Examine MHT’s purported beneficial or preventative effects on heart disease, osteoporosis-related fractures, and risk of various cancers

Question 11

What are some of the harms that were found in dual menopausal hormone therapy?

Answer 11

• Breast cancer (invasive)
• Coronary heart disease
• Dementia
• Gallbladder disease
• Stroke
• Venous thromboembolism
• Urinary incontinence

Question 12

What are some benefits that were found in dual menopausal hormone therapy?

Answer 12

• Diabetes
• All fractures
• Colorectal cancer

Question 13

What are some harms found in estrogen only MHT?

Answer 13

• Dementia
• Gallbladder disease
• Stroke
• Venous thromboembolism
• Urinary incontinence

Question 14

What are some benefits found in estrogen only MTH?

Answer 14

• Breast cancer
• All fractures
• Diabetes

Question 15

What is MHT very effective at treating?

Answer 15

• Vasomotor symptoms and vaginal changes (and associated complications)

Question 16

What is MHT not effective at treating?

Answer 16

• Prevent CVD or dementia

- Benefit on bone and colon cancer are outweighed by the overall risks

Question 17

What is the MHT treatment for younger women?

Answer 17

• Acceptable option for treating severe menopausal symptoms in relatively young and healthy women
• Individulaization with risk-stratification is key
• Some organizations recommending patch over oral therapy

Question 18

What is the MHT treatment for women with vaginal symptoms only?

Answer 18

• Low doses of vaginal estrogen (topical)

Question 19

What is the MHT treatment for women with a uterus?

Answer 19

• Need to take a progestin along with estrogen to prevent uterine cancer
• Women who have had uterus surgically removed able to take estrogen alone

Question 20

What is the MHT treatment for women with risk of blood clots/stroke?

Answer 20

• Both estrogen alone therapy and estrogen with progestin therapy increase risk of blood clots
• Although risks of blood clots and strokes increase with either type of MHT, risk is less in 50-59 year olds

Question 21

What is the MTH treatment for women at risk of breast cancer?

Answer 21

• An increased risk of breast cancer is seen within 3-5 years of continuous estrogen with progestin therapy

Question 22

What is the take home message for MHT?

Answer 22

• Use lowest dose possible to control symptoms

- Treat for the shortest duration possible and reevaluate at least yearly for ongoing need of therapy

Question 23

What is the goal of SERMs?

Answer 23

• Beneficial pro-estrogenic actions in select tissues with beneficial anti-estrogenic actions in other tissues (brain, bone, breast, endometrium)

Question 24

What is the goal of TSECs?

Answer 24

• Combines the unique elements of a SERM with an estrogen compound

Question 25

What are some SERMs?

Answer 25

- Ospemifene | - Clomiphene

Question 26

What are some TSECs?

Answer 26

- Bazedoxifene

Question 27

What are the indications for ospemifene?

Answer 27

- Treatment of moderate-to-severe dyspareunia (a symptom of vulvar and vaginal atrophy of menopause) - Vaginal dryness

Question 28

What is the MOA Of ospemifene?

Answer 28

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

Question 29

What does ospemifene do in the vagina?

Answer 29

- Increase superficial cell growth - Increase vaginal secretions - Decrease vaginal pH - Reduces pain/discomfort during vaginal intercourse

Question 30

What are some side effects of ospemifene?

Answer 30

- Worsening hot flashes/sweating - Estrogenic similar effect on coagulation; albeit at a lower rate than estrogens alone - Endometrial thickening and even hyperplasia

Question 31

What are some contraindications of ospemifene?

Answer 31

- Unusual/abnormal vaginal bleeding - Thromboembolic diseases (CVA/MI/VTE/PE/DVT) - Estrogen related neoplasias (Uterine/Ovarian/Breast

Question 32

What are the indications of bazedoxifene?

Answer 32

- Treatment of moderate-to-severe vasomotor symptoms associated with menopause in women with a uterus - Prevention of postmenopausal osteoporosis in women with a uterus

Question 33

What is the MOA of bazedoxifene?

Answer 33

- Antagonistic activity in endometrium and in breast tissue; but also estrogenic physiological effects, especially in bone

Question 34

How is bazedoxifene different than 1st generation SERMs?

Answer 34

- Does not stimulate endometrial proliferation - Has been shown to destroy HER2 malignant cells, including those resistant to tamoxifen, similar to anti-estrogen drug fulvestrant

Question 35

What are some side effects of bazedoxifene?

Answer 35

- All estrogen related effects due to CE component | - Has the potential of worsening hot flashes/sweating

Question 36

What are some contraindications with bazedoxifene?

Answer 36

- All those that estrogens are

Question 37

What is an anti-estrogen?

Answer 37

- Clomiphene

Question 38

What is the indication of clomiphene?

Answer 38

- Infertility in anovulation women

Question 39

What is the MOA of clompihene?

Answer 39

- Most significant on induction of ovulation in women with amenorrhea, PCOS, and dysfunctional bleeding with anovulatory cycles - Primarily blocks inhibitory actions of estrogens on hypothalamus GnRH and pituitary gonadotropin release

Question 40

What are some side effects of clomiphene?

Answer 40

- Multiple births - Ovarian cysts (ovarian cancer with prolonged use) - Hot flashes - Luteal phase dysfunction (inadequate progesterone production)