Estrogens, Progestins & Androgens Flashcards
What are the 5 phases of the female cycle?
- Menstruation
- Early Follicular Phase
- Late Follicular Phase
- Ovulation
- Luteal Phase
What is Menstruation?
- Uterine lining sheds.
- Hormones are STEADY (and low).
What is Early Follicular Phase?
- Steady levels follicle stimulating hormone (FSH) and luteinizing hormone (LH).
- Primary follicle develops in ovary and it produces estrogen.
- At low concentrations, estrogen inhibits the production of LH and decreases FSH.
What is Late Follicular Phase?
- The follicle matures to a point where it produces high estrogen concentrations.
- This has a positive effect on the production of LH and FSH (spike).
- Estrogen encourages endometrium development in uterus.
Hormone start to spike @ end of this phase
What is Ovulation?
- The spike in LH triggers the release of the ovum from the follicle.
What is Luteal Phase?
- Corpus luteum is left behind from the follicle.
- It produces progesterone, estrogen, and inhibin (not pictured).
- Inhibin blocks release of FSH. (to prevent further follicles from developing)
- Progesterone stimulates endometrial growth & blocks GnRH from hypothalamus.
- As corpus luteum degenerates, the hormone levels drop.
Female Hypothalamus-Pituitary-Gonad Axis:
(+) Feedback (Day 12-14):
- HIGH estrogen [ ]’s
(-) Feedback:
- LOW estrogen [ ]’s
Estrogen receptor’s?
1) Alpha receptor- uterus, ovaries, breast, testis, bone, heart and brain.
2) Beta receptor- prostate, immune system, brain, lungs, bones, blood vessels, bladder, intestine.
(has systemic effects)
Progesterone receptor’s?
- Limited distribution of receptor expression: female genital tract, breast, pituitary
- Weak testis and prostate expression (males)
- produce Progesterone as well but not as much
r. aren’t really found throughout the whole body
What are the effects of estrogen?
- Brain
- Heart & Liver
- Ovary
- Vagina
- Breast
- Uterus
- Bone
What are the effects of Progesterone?
- Substances that prepare the uterus for reception of fertilized ovum. (main place its acting on)
- Increase secretions from the endometrial tissue that has been primed with estrogen.
- Forms a “hostile” environment for sperm penetration (forming an envir. where sperm can penetrate)
- Continued action during pregnancy
- Luteal phase 20- 30 mg/day from ovaries (imp. for dosing drugs)
What is the Broad Drug Classes (General hormone agonists & antagonists)?
- Estrogens (ethinyl estradiol)
- Antiestrogens
- Progestine (L-norgestrel)
- Antiprogestins
- Androgens (testosterone)
- Antiandrogens
What are all the sex hormones produced from?
Cholesterol
Why would someone need drugs that affect female sex hormones (agonists/antagonists)?
- Contraception
- Menopause or Hypogonadism
- Fertility
- Abortion
- Hirsutism
- Acne
- Gender Conformation Therapy
- Osteoporosis
What is Withdrawal bleeding?
- Occurs when there is no progesterone and estrogen in the
blood. - i.e. Menstruation
What is Breakthrough bleeding?
- Any bleeding that occurs despite the presence of steroids.
- It is usually due to high levels of progesterone relative to estrogen.
(potential AE)
What are the 4 gen’s of Estrogen?
Ethinyl Estradiol (1st-4th)
What are the 4 gen’s of Progesterone?
1st - Norethindrone
2nd - Levonorgestrel
3rd - Desogestrel or Norgestimate
4th - Drospirenone
What is Progestin activity?
- Androgenic effects- 1st and 2nd generation progestins- can cause acne and hirsutism
– can also bind to ~ testosterone r. - Newer generations (esp. drospirenone) are more anti-androgenic
- blocks testoderone r. therefore ~ times better for ~ of those SE’s
What is Combination Pills?
3 weeks of hormones, 1 week of placebo (menstruation)
Triphasic - each week the level of P increase & E stays same
Biphasic - 1/2 of 3 weeks there’s 1 level of P & then higher
Monophasic - *most common - EE & NETH @ same
How does a combo of estrogen and progesterone work as an oral contraceptive?
trying to fool body that the woman is in the Luteal Phase
What is the MOA of Oral Contraceptives?
1) Prevent ovulation
* Estrogen and progesterone inhibit the secretion of LH & FSH
2) Prevent sperm entrance
* Thick tenacious mucus secreted under the influence of progesterone
3) Prevent implantation of the fertilized ovum
* Large doses of estrogen alter the motility of the oviduct and change the properties of the endometrium
What is the other benefits of Oral Contraceptives?
- Simple and effective
- Significantly improves menstrual symptoms &
regularity - Decreases relative incidence of disease
- Bacterial pelvic inflammatory disease
- Endometriosis
- ↓ risk of endometrial and ovarian cancer after long term use
- Osteoporosis
What are the risks of Oral Contraceptives?
- Venous Thromboembolism (VTE)
- Estrogen receptors in the liver are responsible for activating blood clotting
factors - Ethinyl estradiol is more potent than natural estrogen - it could hyperactivate the clotting pathway (=> causing blood clots)
- Arterial Thrombosis (MI & stroke) particularly if age >35 and smoking
- Slight increased risk of BREAST & CERVICAL cancer (controversial)
- Hypertension- may develop with age and long term use (b/c of estrogen on CV system)
What is Side Effects of Oral Contraceptives?
*Estrogen is blamed for most of the undesirable side effects.
What are the Side Effects Relating to Estrogen?
- Menstrual irregularities
- Breakthrough bleeding
- Nausea, vomiting
- Headache
- Breast tenderness (fluid
retention) - Weight gain (fluid retention)
- Coagulation risk
- Depression
- Photosensitivity
What are the Side Effects Suggesting Estrogen is Too High?
- Nausea
- Headache
- Breast tenderness
- Bloating
- High blood
pressure
What are the Side Effects Suggesting Estrogen is Too Low?
- Spotting
- Early, mid-cycle
breakthrough bleeding (Days 1-14)
What are the Side Effects Relating to Progestin?
- Menstrual irregularities
- Weight gain*
- Acne*
- Hirsutism*
- Fatigue
- Increased appetite
- Excessive androgenic effects
What are the Side Effects Suggesting Progestin is Too High?
- Headache
- Breast tenderness
- Fatigue
- Mood changes
What are the Side Effects Suggesting Progestin is Too Low?
- Late cycle breakthrough bleeding (Day 15-28)
What are the Other Side Effects of Oral Contraceptives?
May adversely affect fertility when the medication is discontinued after prolonged use.
* In 95% users ovulation resumes within 3 months of discontinuing medication.
* In small proportion of users – may take 1-2 years.