Lecture 7: MHT/SERMS Flashcards
What is the primary therapy for menopausal symptoms?
Estrogen
How does a women with an intact uterus affect the type of pharmacologic treatment used for menopause?
In addition to estrogen they MUST be on progestin!
Why must progestins be given along side estrogens in a women with an intact uterus?
- Estrogen will cause unopposed endometrial proliferation
- Progestin’s oppose effects of estrogen’s.
What are 3 things that estrogen therapy causes a decreased production/activity of?
- ↓ cholesterol (TC/LDL-C)
- ↓ anti-thrombin III
- ↓ osteoclast activity (bone turnover)
What are 5 things that estrogen therapy causes increased production/activity of?
- ↑ TAG’s and HDL-C
- ↑ clotting factors
- ↑ platelet aggregation
- ↑ Sodium and fluid retention
- ↑ Thyroid Binding Globulin (TBG)
List 7 potential AE’s associated with a combo of estrogen + progestin used for treatment of postmenopausal women.
- Breast cancer
- CHD
- Dementia (aged 65 y/o +)
- GB disease
- Stroke
- Venous thromboembolism
- Urinary incontinence
List 3 potential benefits associated with a combo of estrogen + progestin used for treatment of postmenopausal women.
- Improvement of diabetes
- Less risk of all fractures
- Less risk of colorectal cancer
List 5 potential AE’s associated with estrogen used for treatment of postmenopausal women.
- Dementia (aged 65 y/o +)
- GB disease
- Stroke
- Venous thromboembolism
- Urinary incontinence
List 3 potential benefits associated with estrogen thrapy used for treatment of postmenopausal women.
- ↓ risk of breast cancer (invasive)
- ↓ risk of all fractures
- Improvement of diabetes
The women’s health initiative study found that MHT is very effective for what?
- Minimize/treat vasomotor sx’s and vaginal changes (and their associated complications)
- Do NOT use for prevention of CVD or dementia and do NOT use solely for benefit on bone or colorectal cancer
What are the 2 SERM’s we need to know for this exam?
- Ospemifene
- Clomiphene
What is the tissue selective estrogen complexes (TSECs) we need to know for this exam?
Bazedoxifene
What is the clinical indication for the SERM, Ospemifene?
- Tx of moderate-to-severe dyspareunia (painful intercourse)
- A sx of vulvar and vagnal atrophy (VVA) of menopause
Explain the MOA of the SERM, Ospemifene.
- Estrogen agonist at ER’s of the vagina –> ↑ superficial cell growth, ↑ vaginal secretions, ↓ vaginal pH, ↓ pain/discomfort during intercourse
- Estrogen antagonist at ER’s in the breast
What is the clinical indication for using the SERM, Clomiphene?
Infertility in anovulatory women
What is the MOA of the SERM, Clomiphene?
- Primarily blocks inhibitory actions of estrogen on hypothalamus GnRH and pituitary gonadotropin release (anti-estrogen)
- ↑ gonadotropin (FSH, LH) secretion thereby stimulating the ovaries to develop oocyte follicles
Which patients are the most significant effects seen in when treated with the SERM, Clomiphene?
Induction of ovulation in women w/ amenorrhea, PCOS,anddysfunctional bleedingw/anovulatory cycles
What are the 2 clinical indications for the use of the TSEC, Bazedoxifene (w/ CE)?
- Tx of moderate-to-severe vasomotor sx’s assoc. w/ menopause in women with a uterus
- Prevention of post-menopausal osteoporosis (along w/ Ca2+ and Vit D) in women with a uterus
What is the MOA of the TSEC, Bazedoxifene?
- Antagonist activity in endometrium (replaces progestin-concept in women with an intact uterus) and in breast tissue
- Has estrogenic agonist effects, especially in bone (CE agent)
How does Bazedoxifene differ from the 1st gen. SERMS as far as effects and utility?
- Does NOT stimulate endometrial proliferation
- Has been shown (lab) to destroy HER2 malignant cells (SERDs), including cells resisten to Tamoxifen, similar to anti-estrogen drug Fluvestrant)
- Less vaginal bleeding than CE w/ progestin therapy
