1. MHT Flashcards
What are symptoms of menopause (body is not making enough estrogen)?
- Hot flashes
- Night sweats
- Vaginal dryness/painful intercourse/sexual DYS
- Sleep problems
- Mood/cognitive problems
- Urinary incontinence
During menopause, ________ and __________ are also affected.
- Bones (osteopenia, -porosis, fractures)
- CV (ACS/ MI, CVD)
What is the primary therapy for menopausal symptoms?
Estrogen
Tx for menopause in:
- Women with intact uterus
- Women without an intact uterus
- WITH uterus: estrogen + progestin
- WITHOUT uterus: estrogen
Why must a woman with an intact uterus be treated with [estrogen + progestin]?
- Estrogen alone will cause endometrial proliferation, which can lead to hyperplasia and endometrial carcinoma.
- Progestin’s oppose effects of estrogen’s.
What are the 4 estrogens available for use in menopausal hormone therapy?
1) Estradiol
2) Conjugated estrogens (CE)
3) Esterified estrogens (EE)
4) Estropipate: Crystallized estrone solubilized w/ sulfate and then 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)
MOA of Estrogen?
- Estrogen binds to a/B- estrogen receptors on the cell membrane.
- Transferred to nucleus => increased gene and protein expression
- Physiological response.
Estrogen causes a ↓ production/activity of?
- Cholesterol (TC/LDL-C)
- Anti-thrombin III
- Osteoclast activity (bone turnover)
Estrogen causes a ↑ production/activity of?
- TAG’s and HDL-C
- Clotting factors
- Platelet aggregation
- Na+ and fluid retention
- Thyroid Binding Globulin (TBG)
We do NOT want to give Estrogen to who?
Those at-risk of clotting.
List 7 potential AE’s associated with a combo of estrogen + progestin used for treatment of postmenopausal women with a uterus.
- 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 incidence of all fractures
- Less incidence 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.
- ↓ incidence of breast cancer (invasive)
- ↓ incidence of all fractures
- Improvement of diabetes
The Women’s Health Initiative (WHI) study found that MHT is very effective for what?
- ↓/treat vasomotor sx’s and vaginal changes (and their associated complications)
- But do NOT use to prevent CVD or dementia and to help bones or prevent colorectal cancer
What is the recommendation/agreement for using MHT therapy in younger women?
Can be used to tx 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?
Treat with low-dose topical vaginal estrogen.
Which age group has less risk of blood clots/stroke from MHT therapy?
Both estrogen and estrogen + progestin increase risk of blood clots, however risk is lowest in 50-59YO.
There is an increased risk of breast cancer with MHT when treated for how long?
How does this alter how we treat?
- 3-5 years of continous estrogen + progestin
- Use it at the lowest dose possible for the shortest amount of time.
Do the risk and benefits of MHT continue even when MHT is stopped?
No. Risks and benfits are attenuated/eliminated.
MHT therapy is used for moderate-severe vasomotor symptoms by giving…
lowest dose to control sx for the shortest amount of time (by re-evaulating) pt.
What are SERMs and TSECs?
- SERMs (selective-estrogen receptor modulators) bind selectively to receptors in tissues with GOOD pro-estrogenic actions and beneficial (non-harmful) anti-estrogenic (ANT) in other tissues, like bone, brain, breast and endometrium
- TSECs (tissue selective estrogen complexes) are SERMS + estrogen compound.
2 SERM’s
- Ospemifene
- Clomiphene
1 TSEC
- Bazedoxifene (in US, only used as a combo w/ CE)
What is the clinical indication for the SERM, Ospemifene?
- Tx moderate-to-severe dyspareunia (painful intercourse), a sx of vulvar and vagnal atrophy (VVA) during menopause.
If a patient presents with menopause and their CC is dysparenuria?
- Ospemifine
- Tropical estrogen cream
MOA of Ospemifene (SERM) for Dyspareunia.
- Acts as a estrogen AGO by binding to ER’s in the vagina and estrogen ANT in breast tissue (anti-estrogenic) –>
- ↑ superficial cell growth,
- ↑ vaginal secretions,
- ↓ vaginal pH,
- ↓ pain/discomfort during intercourse
AE’s associated with the SERM, Ospemifene?
- Worsening of hot flashes/sweating
- Acts similar to estrogen in terms of coagulation (↑ risk of stroke/VTE; but at lower rate than estrogens alone)
- Endometrial thickening (proliferation) and hyperplasia/malignancy, but no cases in clinical trials yet
What are the contraindications for using the SERM, Ospemifene, which are the same as estrogens.
- 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?
Has purely anti-estrogenic actions to stimulate ovulation in Infertile women.
What is the MOA of the SERM, Clomiphene?
- Blocks inhibitory actions of estrogen on hypothalamus GnRH and pituitary gonadotropin release (anti-estrogen) =>
- ↑ gonadotropin (FSH, LH) secretion => stimulating the ovaries to develop oocyte follicles
Which patients are the most significant effects seen in when treated with the SERM, Clomiphene?
Induces ovulation in women w/ amenorrhea, PCOS, and dysfunctional bleeding w/ anovulatory cycles.
What are the 4 AE’s associated with the SERM, Clomiphene?
- Multiple births (99% of times = twins)
- Ovarian cysts —> ovarian cancer w/ prolonged use (limit use to 3 cycles)
- Hot flashes
- Luteal-phase dysfunction –> inadequate progesterone prod.
2 clinical indications for the TSEC, Bazedoxifene (w/ CE)?
- Tx moderate-to-severe vasomotor sx’s in menopausal women with a uterus.
- Prevent post-menopausal osteoporosis (along w/ Ca2+ and Vit D) in women with a uterus
Can Bazedoxifene (w/CE) be used as a progestin and estrogen in people with uterus?
YES. It is usually the 2nd go to in poeple with sx.
MOA of the TSEC, Bazedoxifene?
- ANT activity in endometrium (replaces progestin-concept in women with an intact uterus) and in breast tissue
- Has estrogenic AGO 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
- Destroy HER2 malignant cells (SERDs), including cells resistant to Tamoxifen (similar to anti-estrogen drug Fluvestrant)
- Less vaginal bleeding than [CE w/ progestin]
AE’s and CI associated with the TSEC, Bazedoxifene?
AE
- ALL AE are due to estrogen, because it has CE.
- Bazedoxifene-specific AE: can worsen flashes/sweating (similar to Tamoxifen, Raloxifene and Ospemifene
CI
- CI in all cases estrogens are CI.
