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Endo/Repro > MHT and SERMS > Flashcards

MHT and SERMS Flashcards

1
Q

What are some symptoms of menopause?

A
  • Hot flashes
  • Night sweats
  • Vaginal dryness/painful intercourse/sexual dysfunction
  • Sleep disturbances
  • Mood/cognitive issues
  • Urinary incontinence
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2
Q

What is the primary therapy for menopausal symptoms?

A
  • Estrogen
  • With/without the addition of progestin
  • Women with an intact uterus must also be on a progestin
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3
Q

Why must a women with a uterus be on a progestin as well as estrogen?

A
  • To reduce the risk of endometrial hyperplasia/carcinoma from unopposed tissue proliferation with prolonged duration
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4
Q

What are the four estrogenic forms for menopausal hormone therapy?

A
  • 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
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5
Q

What are some available progestinic components used for menopausal hormone therapy?

A
  • Medroxyprogesterone
  • Methyltestosterone
  • Progesterone
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6
Q

What is the MOA of estrogen?

A
  • Bind to estrogen receptors in various tissues, transferred into nucleus resulting in increased gene and ultimately protein, expression resulting in physiological responses
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7
Q

What are the effects of estrogen?

A
  • 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
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8
Q

What does estrogen decrease in the body?

A
  • Cholesterol
  • Anti-thrombin III
  • Osteoclastic activity (bone turnover)
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9
Q

What does estrogen increase in the body?

A
  • Triglycerides and HDL-C
  • Clotting factor
  • Platelet aggregation
  • Sodium/fluid retention
  • Thyroid binding globulin (TBG)
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10
Q

What was the objective of the women’s health initiative study?

A
  • Examine MHT’s purported beneficial or preventative effects on heart disease, osteoporosis-related fractures, and risk of various cancers
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11
Q

What are some of the harms that were found in dual menopausal hormone therapy?

A
  • Breast cancer (invasive)
  • Coronary heart disease
  • Dementia
  • Gallbladder disease
  • Stroke
  • Venous thromboembolism
  • Urinary incontinence
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12
Q

What are some benefits that were found in dual menopausal hormone therapy?

A
  • Diabetes
  • All fractures
  • Colorectal cancer
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13
Q

What are some harms found in estrogen only MHT?

A
  • Dementia
  • Gallbladder disease
  • Stroke
  • Venous thromboembolism
  • Urinary incontinence
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14
Q

What are some benefits found in estrogen only MTH?

A
  • Breast cancer
  • All fractures
  • Diabetes
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15
Q

What is MHT very effective at treating?

A
  • Vasomotor symptoms and vaginal changes (and associated complications)
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16
Q

What is MHT not effective at treating?

A
  • Prevent CVD or dementia

- Benefit on bone and colon cancer are outweighed by the overall risks

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17
Q

What is the MHT treatment for younger women?

A
  • 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
18
Q

What is the MHT treatment for women with vaginal symptoms only?

A
  • Low doses of vaginal estrogen (topical)
19
Q

What is the MHT treatment for women with a uterus?

A
  • Need to take a progestin along with estrogen to prevent uterine cancer
  • Women who have had uterus surgically removed able to take estrogen alone
20
Q

What is the MHT treatment for women with risk of blood clots/stroke?

A
  • 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
21
Q

What is the MTH treatment for women at risk of breast cancer?

A
  • An increased risk of breast cancer is seen within 3-5 years of continuous estrogen with progestin therapy
22
Q

What is the take home message for MHT?

A
  • Use lowest dose possible to control symptoms

- Treat for the shortest duration possible and reevaluate at least yearly for ongoing need of therapy

23
Q

What is the goal of SERMs?

A
  • Beneficial pro-estrogenic actions in select tissues with beneficial anti-estrogenic actions in other tissues (brain, bone, breast, endometrium)
24
Q

What is the goal of TSECs?

A
  • Combines the unique elements of a SERM with an estrogen compound
25
Q

What are some SERMs?

A
  • Ospemifene

- Clomiphene

26
Q

What are some TSECs?

A
  • Bazedoxifene
27
Q

What are the indications for ospemifene?

A
  • Treatment of moderate-to-severe dyspareunia (a symptom of vulvar and vaginal atrophy of menopause)
  • Vaginal dryness
28
Q

What is the MOA Of ospemifene?

A
  • Functions as estrogen agonist by binding to ER’s in vagina, but also anti-estrogenic on breast
29
Q

What does ospemifene do in the vagina?

A
  • Increase superficial cell growth
  • Increase vaginal secretions
  • Decrease vaginal pH
  • Reduces pain/discomfort during vaginal intercourse
30
Q

What are some side effects of ospemifene?

A
  • Worsening hot flashes/sweating
  • Estrogenic similar effect on coagulation; albeit at a lower rate than estrogens alone
  • Endometrial thickening and even hyperplasia
31
Q

What are some contraindications of ospemifene?

A
  • Unusual/abnormal vaginal bleeding
  • Thromboembolic diseases (CVA/MI/VTE/PE/DVT)
  • Estrogen related neoplasias (Uterine/Ovarian/Breast
32
Q

What are the indications of bazedoxifene?

A
  • Treatment of moderate-to-severe vasomotor symptoms associated with menopause in women with a uterus
  • Prevention of postmenopausal osteoporosis in women with a uterus
33
Q

What is the MOA of bazedoxifene?

A
  • Antagonistic activity in endometrium and in breast tissue; but also estrogenic physiological effects, especially in bone
34
Q

How is bazedoxifene different than 1st generation SERMs?

A
  • Does not stimulate endometrial proliferation
  • Has been shown to destroy HER2 malignant cells, including those resistant to tamoxifen, similar to anti-estrogen drug fulvestrant
35
Q

What are some side effects of bazedoxifene?

A
  • All estrogen related effects due to CE component

- Has the potential of worsening hot flashes/sweating

36
Q

What are some contraindications with bazedoxifene?

A
  • All those that estrogens are
37
Q

What is an anti-estrogen?

A
  • Clomiphene
38
Q

What is the indication of clomiphene?

A
  • Infertility in anovulation women
39
Q

What is the MOA of clompihene?

A
  • 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
40
Q

What are some side effects of clomiphene?

A
  • Multiple births
  • Ovarian cysts (ovarian cancer with prolonged use)
  • Hot flashes
  • Luteal phase dysfunction (inadequate progesterone production)

Endo/Repro (31 decks)

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