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!
What are the 4 estrogens available for use in menopausal hormone therapy?
1) Estradiol
2) Conjugated estrogens (CE)
3) Esterified estrogens (EE)
4) Estropipate: estrone solubilized w/ sulfate and stabilized w/ piperazne
What are the 3 progestin drugs available for menopausal hormone therapy?
1) Medroxyprogesterone (MPA alone or with CE)
2) Methyltestosterone (alone or with EE)
3) Progesterone (alone)
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 adverse effects’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 is the recommendation/agreement for using MHT therapy in younger women?
MHT is an acceptable option for tx of moderate-severe menopausal sx’s in relatively young (up to age 59 or within 10 years of menopause)
What is the recommendation/agreement for MHT therapy in women with vaginal sx’s only?
Preferred tx are low doses of vaginal estrogen (topical)
Which age group has less risk of blood clots/stroke from MHT therapy?
50-59 y/o group
There is an increased risk of breast cancer with MHT seen within how long of treatment?
- 3-5 years of continous estrogen + progestin
- Use it at the lowest dose possible for the shortest amount of time.
What are the 2 Selective Estrogen Receptor Modulators (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 Selective Estrogen Receptor Modulators (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 are the AE’s associated with the SERM, Ospemifene?
- Worsening of hot flashes/sweating
- Estrogenic-similar effects on coagulation (↑ risk of stroke/VTE; but at lower rate than estrogens alone)
- Endometrial thickening (proliferation) and even hyperplasia —> concern for malignancy, but no cases in clinical trials yet
What are the contraindications for using the SERM, Ospemifene?
- Unusual/abnormal vaginal bleeding
- Thromboembolic diseases: CVA or MI or VTE or PE or DVT
- Caution with use in smokers
- Estrogen-related neoplasia’s: uterine or ovarian or 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
In 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
What are the AE’s associated with the Tissue Selective Estrogen Complexes (TSEC), Bazedoxifene?
- ALL estrogen-related effects (due to CE component)
- Bazedoxifene-specific: has the potential of worsening hot flashes/sweating (similar to Tamoxifen, Raloxifene and Ospemifene)
What are the 4 AE’s associated with the SERM, Clomiphene?
- Multiple births
- Ovarian cysts —> ovarian cancer w/ prolonged use (limit use to 3 cycles)
- Hot flashes
- Luteal-phase dysfunction –> inadequate progesterone prod.
