MHTs, SERMs, & TSECs Flashcards
Post-menopause is not medically defined until _______ of complete amenorrhea
12 months
The primary therapy for menopausal symptoms is _____
Estrogen
The primary therapy for menopausal sxs is estrogen. When would you also add progestin?
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
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?
Hormonal contraceptives — provide hormone regulation to reduce symptoms while also providing pregnancy protection
Estrogenic forms of menopausal hormone therapy
Estradiol
Conjugated estrogens (CE)
Esterified estrogens (EE)
Estropipate
[all of these have numerous dosage forms available]
Progestinic forms of menopausal hormone therapy
Medroxyprogesterone (MPA) — alone or with CE
Methyltestosterone — alone or with EE
Progesterone
Estrogen’s cellular MOA
Binds ER in various tissues, transferred into nucleus resulting in increased gene and protein expression leading to physiologic responses
Biochemical/physiological effects of estrogen MHT
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)
What are the WHI studies?
Examined MHT’s purported beneficial or preventive effects on heart disease, osteoporosis-related fractures, and risk of various cancers (breast, endometrial, colon)
Harms vs. benefits found in WHI studies in women taking combined estrogen+progestin MHT
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
Harms vs. benefits found in WHI studies in women taking estrogen alone for MHT
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
The summary of WHI findings state that MHT very effectively minimizes/treats what 2 symptoms of menopause (and their associated complications)?
Vasomotor symptoms
Vaginal changes
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
True
[also should not be used to prevent CVD or dementia]
What is the recommendation regarding MHT use in younger women?
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
What is the recommendation regarding MHT in women with vaginal symptoms only?
Preferred treatments are low doses of vaginal estrogen (topical)
What is the recommendation regarding MHT in women at risk of blood clots/stroke?
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
When is an increased risk of breast cancer seen in patients on MHT?
Within 3-5 years of continuous estrogen with progestin therapy
T/F: risks and benefits of MHT are attenuated/eliminated several years after therapy is stopped
True
What is the goal of selective estrogen receptor modulators (SERMs)?
Beneficial pro-estrogenic (agonist) actions in select tissues with beneficial (or non-harmful) anti-estrogenic (antagonist) actions in other tissues
What is the goal of tissue selective estrogen complexes?
Combines unique elements of a SERM with an estrogen compound
2 major SERMs
Ospemifene
Clomiphene
TSEC currently only available as a combo with CE
Bazedoxifene
Only indication for SERM ospemifene
Treatment of moderate-to-severe dyspareunia (painful intercourse)
[used if pt doesn’t want topical estrogen]
MOA of osepemifene used for dyspareunia
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
Side effects of ospemifene
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)
Contraindications to ospemifene
Same as estrogens!
Unusual/abnormal vaginal bleeding
Thromboembolic diseases (exercise caution in smokers)
Estrogen-related neoplasias (uterine, ovarian, breast)
Indications for bazedoxifene w/CE
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)
MOA of bazedoxifene w/CE
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
How is bazedoxifine (2nd gen) different from 1st gen SERMs?
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
Side effects of 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)
Contraindicated in all situations estrogens are due to CE component
Example of anti-estrogen medication indicated in cases of infertility in anovulatory women
Clomiphene
MOA of clomiphene
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
Side effects of Clomiphene
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)
