Estrogen Therapy Flashcards
What is the main estrogen produced by the ovary
Estradiol-17B
Name 2 weak natural estrogens
- Estriol
2. Estrone
Tell me again how estradiol-17B is made?
Aromatization reaction of testosterone or androstenedione. Catalyzed by aromatase enzyme (CYP19)
Where do you find aromatase?
- Granulosa cells of the ovary
- Sertoli and leydig cells
- Adipose stroma
- Bone
- Brain (interesting)
In a premenopausal woman, where does most of the circulating estrogen come from?
The ovaries
What type of estrogen does the liver make?
Estriol and estrone. Catalyzed by type II hydroxysteroid dehydrogenase.
In a postmenopausal woman, where does most of the circulating estrogen come from?
Estrone produced by adipose tissue
What are the effects of estrogen in utero?
Formation of the:
- Vagina
- Uterus
- Fallopian tubes
What are the effects of estrogen when girls go through puberty, the best time of your life
- Pubic and axillary hair growth
- Distribution of body fat
- Ductal and stromal development of breast
- Endometrial development
- Long bone development and eventual epiphyseal plate closure
What are some of the metabolic effects of estrogen?
- increased bone mass (cause we ladies gots the strongest bones)
- Increased triglycerides (cause you ladies are fat) and reduces serum cholesterol
What modification is needed to make estrogen preparations orally action
17alpha
17a ethinyl estradiol is the pharm prep of estrogen that we need to know
What kind of disease would you consider using estrogen therapy for? (a bit intuitive)
- Hypogonadism: being replacement therapy between 11-13 yo and then switch to a 12a ethinyl estoradiol/progesterione OCP
- Menopausal hormone therapy
We know that estrogen helps treat the symptoms of menopause. What specifically is estrogen helping with?
- Decreasing bone fractures
- Hot flashes (vasomotor sx)
- Vaginal dryness
- Urogenital atrophy
- Memory problems
What are the consequences of hormone replacement therapy
Increased risk for MI and endometrial carcinoma
What is norethindrone acetate. Do we still use this drug?
Its a estrogen progesterone combined hormone replacement therapy. No, the study was halted in 2002 because of increased risks of MI, stroke, blood clots and breast cancer
There are three SERMS we need to know. (Selective estrogen receptor modulators). What are they? (more details on them later)
Remember the FENce drugs (women are hopping back over the fence from menopause to their pre-menopause estrogen levels)
- TamoxiFEN
- RaloxiFENe
- OspemiFENe
(The FENce is now TORn, n=nothing)
TamoxiFEN. How does it’s effect differ based on the tissue it acts on?
*Breast: antagonist, decreased risk of cancer
Bone: agonist, decreased risk of osteoporosis
Endometrium: agonist, increased risk of cancer
Liver: agonist, increase risk of venous thrombosis
RaloxiFENe. Describe its effect on bone, breast, endometrium
*Breast: antagonist, decreased risk of cancer
Bone: partial agonist, decreased risk of osteoporosis
Endometrium: antagonist, decreased risk of cancer
Ospemifene. Why is this SERM so special?
It is the ONLY SERM that has estrogen like effects on the vagina. In post-menopausal women there can be vaginal atrophy leading to dyspareunia (pain during intercourse). This drug can help with that and also:
Bone: agonist, decreased risk of osteoporosis
Endometrium: antagonist: decreased risk of cancer
Breast: antagonist, decreased risk of cancer
What is the one estrogen synthesis inhibitor we are responsible for knowing?
Letrozole
How does letrozole work and what do we use it for?
It is an aromatase inhibitor that is used to treat breast cancer. Used first line or second line with tamoxifen.
Side effect: hot flashes
