Endocrine 6 (Reproduction) Flashcards
What hormone regulates the menstrual cycle?
GnRH regulates the secretion of FSH and LH
Endogenous Estrogens
- Examples
Estrone, Estradiol, Estriol
Estradiol = Most Potent
Synthetic Estrogens
- Examples
Ethinylestradiol, Mestranol
Estrogen
- Receptor Signalling
Reproductive Action
- Nuclear Estrogen Receptors (ER)
–> ER alpha and ER beta
–> Transcription Factors that regulate gene expression
Vascular Action
- GPCR
–> GPR30 or GPER
1. Activation of endothelial nitric oxide synthase (eNOS)
2. Increases NO
3. Vasodilation
Combined Pill
- Contains?
Ethinylestradiol (Synthetic Estrogen)
- Natural Estrogen are susceptible to hepatic metabolism
2nd Generation Progestogens
- Norethisterone, Levonorgestrel, Ethynodiol
or
3rd Generation Progestogens
- Desogestrel, Gestodene
Combined Pill
- MOA
Estrogen increases Negative Feedback on anterior pituitary
- Suppresses Ovarian Follicular Development
Progestogen increases Negative Feedback on anterior pituitary
- Inhibit LH secretion –> Prevents Ovulation
Both work in combination to make reproductive tract unsuitable for contraception and implantation
Combined Pill
- Acne: Estrogen vs Progesterone
Acne is caused by free androgens
Estrogen: Increases sex hormone binding globulin that remove free androgens
–> Decrease Acne
Progesterone: Increases amount of androgen
–> Increases Acne
Combined Pill
- Adverse Effect
Thromboembolism
- Patients that smoke or have a history of hypertension should avoid 3rd generation Progestogens
Increase Blood Pressure in some Women
- Caused by increase in circulating angiotensinogen
- Stop using combine pill and switch to a progestogen only therapy
Combined Pill
- Beneficial Effect
Reduced risk in ovarian and endometrial cancer
Decreased menstrual symptoms
Reduced iron deficiency anemia
Hormonal Contraceptives
- Breast Cancer
Actually do not increase the risk of breast cancer
- Only appears like it does due to greater monitoring when using contraceptives
- Allows us to catch the cancer early
2nd Generation Progestogen vs
3rd Generation Progestogen
3rd gens are less likely to cause acne
Higher risk for thromboembolism
Progestogen Only Pill
- Contains?
Norethindrone (1st Generation)
or
Ethynodiol (2nd Generation)
Progestogen Only Pill
- MOA
- Makes cervical mucus inhospitable to sperm
- Inhibits implantation (Altering endometrium)
- Alters motility and secretions of fallopian tubes
Alternative for people who experience blood pressure increase from estrogen
Postcortical Contraception
Oral Dose of Levonorgestrel
- Used in emergency, dose is repeated 12 hours later
- Causes nausea and vomit
–> Take with Dimenhydrinate (Gravol)
Long-Acting Progestogen-Only Contraception
Depot Medroxyprogesterone
- Given intramuscularly (Slow release of progestogen)
- Menstrual irregularities are common
- Infertility may persist for months even after stopping treatment
Non-Biodegradable Capsule Contraception
Subcutaneous Insertion of Levonorgestrel
- Slowly releases progestogen for 5 years
Oxytocin
- Regulation
Released facilitated by:
- Cervical dilation
- Estrogen causes greater expression of receptor
Oxytocin
- MOA
Usually given by IV
1. Binds to GPCR (Gq)
2. PLC breaks PIP2 into IP3 and DAG
3. IP3 causes an increase in intracellular calcium
4. Calcium activates Calmodulin
5. Calmodulin stimulates MLCK
6. MLCK induce uterine contraction
Also causes a release of prostaglandins that cause uterine contraction
Oxytocin
- Adverse Effects
- Hypotension (When administered rapidly)
- High dose can cause sustained contraction
–> Reduces blood flow and O2 delivery
–> Fetal distress and potentially death
Have to do slow increments up to maximum dose
What causes uterine contractions
Oxytocin
- Estrogen increase expression of receptor
Cervical dilation
Prostaglandins
Ergometrine
- MOA
May act on Alpha-Adrenoceptor and partly on 5-HT Receptors
- Stimulates Uterine Contraction
Stronger effect on relaxed uterus
Minimal effect on contracted uterus
Alpha-Adrenoceptor
- Stimulates Uterine Contraction
Beta Adrenoceptor
- Inhibits Uterine Contraction
Ergometrine
- Adverse Effects
Vomiting (Effects D2 receptors in the chemoreceptor trigger zone)
- Use D2 antagonist to treat vomiting
–> Domperidone
–> Metoclopramide
–> Profenamine
Mifepristone
- MOA
Competitive Antagonist / Partial Agonist of Progesterone
- Sensitizes uterine muscle to progesterone
- Allows for a lower dose of prostaglandin
Followed by a prostaglandin to induce myometrial contraction and expel the fetus
- Misoprostol (Prostaglandin E1 Analogue)
- Gemeprost (Prostaglandin E1 Analogue)
Atosiban
- MOA
Competitive antagonist of oxytocin receptor
- Delays labour
Prevents increase of IP3
- No increase in intracellular calcium
- No increase in MLCK for uterine contraction
Suppresses oxytocin-induced release of prostaglandins
