MHT and SERMS Flashcards
What are some symptoms of menopause?
- Hot flashes
- Night sweats
- Vaginal dryness/painful intercourse/sexual dysfunction
- Sleep disturbances
- Mood/cognitive issues
- Urinary incontinence
What is the primary therapy for menopausal symptoms?
- Estrogen
- With/without the addition of progestin
- Women with an intact uterus must also be on a progestin
Why must a women with a uterus be on a progestin as well as estrogen?
- To reduce the risk of endometrial hyperplasia/carcinoma from unopposed tissue proliferation with prolonged duration
What are the four estrogenic forms for menopausal hormone therapy?
- 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
What are some available progestinic components used for menopausal hormone therapy?
- Medroxyprogesterone
- Methyltestosterone
- Progesterone
What is the MOA of estrogen?
- Bind to estrogen receptors in various tissues, transferred into nucleus resulting in increased gene and ultimately protein, expression resulting in physiological responses
What are the effects of estrogen?
- 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
What does estrogen decrease in the body?
- Cholesterol
- Anti-thrombin III
- Osteoclastic activity (bone turnover)
What does estrogen increase in the body?
- Triglycerides and HDL-C
- Clotting factor
- Platelet aggregation
- Sodium/fluid retention
- Thyroid binding globulin (TBG)
What was the objective of the women’s health initiative study?
- Examine MHT’s purported beneficial or preventative effects on heart disease, osteoporosis-related fractures, and risk of various cancers
What are some of the harms that were found in dual menopausal hormone therapy?
- Breast cancer (invasive)
- Coronary heart disease
- Dementia
- Gallbladder disease
- Stroke
- Venous thromboembolism
- Urinary incontinence
What are some benefits that were found in dual menopausal hormone therapy?
- Diabetes
- All fractures
- Colorectal cancer
What are some harms found in estrogen only MHT?
- Dementia
- Gallbladder disease
- Stroke
- Venous thromboembolism
- Urinary incontinence
What are some benefits found in estrogen only MTH?
- Breast cancer
- All fractures
- Diabetes
What is MHT very effective at treating?
- Vasomotor symptoms and vaginal changes (and associated complications)
What is MHT not effective at treating?
- Prevent CVD or dementia
- Benefit on bone and colon cancer are outweighed by the overall risks
What is the MHT treatment for younger women?
- 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
What is the MHT treatment for women with vaginal symptoms only?
- Low doses of vaginal estrogen (topical)
What is the MHT treatment for women with a uterus?
- Need to take a progestin along with estrogen to prevent uterine cancer
- Women who have had uterus surgically removed able to take estrogen alone
What is the MHT treatment for women with risk of blood clots/stroke?
- 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
What is the MTH treatment for women at risk of breast cancer?
- An increased risk of breast cancer is seen within 3-5 years of continuous estrogen with progestin therapy
What is the take home message for MHT?
- Use lowest dose possible to control symptoms
- Treat for the shortest duration possible and reevaluate at least yearly for ongoing need of therapy
What is the goal of SERMs?
- Beneficial pro-estrogenic actions in select tissues with beneficial anti-estrogenic actions in other tissues (brain, bone, breast, endometrium)
What is the goal of TSECs?
- Combines the unique elements of a SERM with an estrogen compound
What are some SERMs?
- Ospemifene
- Clomiphene
What are some TSECs?
- Bazedoxifene
What are the indications for ospemifene?
- Treatment of moderate-to-severe dyspareunia (a symptom of vulvar and vaginal atrophy of menopause)
- Vaginal dryness
What is the MOA Of ospemifene?
- Functions as estrogen agonist by binding to ER’s in vagina, but also anti-estrogenic on breast
What does ospemifene do in the vagina?
- Increase superficial cell growth
- Increase vaginal secretions
- Decrease vaginal pH
- Reduces pain/discomfort during vaginal intercourse
What are some side effects of ospemifene?
- Worsening hot flashes/sweating
- Estrogenic similar effect on coagulation; albeit at a lower rate than estrogens alone
- Endometrial thickening and even hyperplasia
What are some contraindications of ospemifene?
- Unusual/abnormal vaginal bleeding
- Thromboembolic diseases (CVA/MI/VTE/PE/DVT)
- Estrogen related neoplasias (Uterine/Ovarian/Breast
What are the indications of bazedoxifene?
- Treatment of moderate-to-severe vasomotor symptoms associated with menopause in women with a uterus
- Prevention of postmenopausal osteoporosis in women with a uterus
What is the MOA of bazedoxifene?
- Antagonistic activity in endometrium and in breast tissue; but also estrogenic physiological effects, especially in bone
How is bazedoxifene different than 1st generation SERMs?
- Does not stimulate endometrial proliferation
- Has been shown to destroy HER2 malignant cells, including those resistant to tamoxifen, similar to anti-estrogen drug fulvestrant
What are some side effects of bazedoxifene?
- All estrogen related effects due to CE component
- Has the potential of worsening hot flashes/sweating
What are some contraindications with bazedoxifene?
- All those that estrogens are
What is an anti-estrogen?
- Clomiphene
What is the indication of clomiphene?
- Infertility in anovulation women
What is the MOA of clompihene?
- 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
What are some side effects of clomiphene?
- Multiple births
- Ovarian cysts (ovarian cancer with prolonged use)
- Hot flashes
- Luteal phase dysfunction (inadequate progesterone production)
