Female Reproductive Drugs - Trachte Flashcards
What can reproductive drugs be used for?
Promoting folliculogenesis Hyperstimulation of follicles Control the timing of ovulation Inducing Ovulation Uterine Fibroid treatment Treatment of hormone sensitive cancers Maintaining pregnancy ***Contraception Emergency contraception Inducing labor (also medical abortion, but Dr. Trachte failed to mention this)
What can you do to promote folliculogenesis in women with hypothalamic anovulatory function?
Administer both FSH and LH by daily injection
For superovulation in normal ovulatory women
FSH/LH on d 2-3 of menstrual cycle
What can you do to promote folliculogenesis in women with endogenous estrogen activity and normal hypothalamic-pituitary-ovarian function?
Usually use clomiphene citrate an estrogen antagonist which induces FSH secretion
What are the two urinary derived human gonadotropins (FSH & LH) pooled from postmenopausal women, concentrated and purified?
menotropins (Pergonal®; injected; FSH and LH activity)
Pergonal with hCG given in sequence for ovulation in anovulatory women and for production of multiple follicles.
urofolitropin (Metrodin®; injected; FSH activity)
Metrodin with hCG given in sequence for induction of ovulation of patients with polycystic ovarian disease (w/ high FSH/LH and failed clomiphene citrate therapy)
What are the two recombinant human gonadotropins that are available immediately and with batch to batch consistency?
follitropin a (Gonal-f; FSH) and follitropin b (Follistim®; FSH) the preparations of a and b are synthesized by the same recombinant technology resulting in identical dimeric α-FSH and β-FSH subunits that differ in the glycosylation and purification procedures.
Used to induce follicle development and when coupled with hCG induction of ovulation.
What drug is an estrogen antagonist in hypothalamus (may have agonist effects elsewhere) that blocks ER signaling in hypothalamus and anterior pituitary and stimulates release of GnRH and gonadotropins, therefore it is used as fertility drug to induce (multiple) ovulation(s)?
Clomiphene citrate = estrogen receptor antagonist
What are the side effects of Clomiphene citrate?
Toxicity: Hot flashes, ovarian hyperstimulation syndrome
- Moderate cases of OHSS 3-6% of cycles
- Severe cases of OHSS 0.1-3% of all cycles
- OHSS in high risk women approaches 20% of all cycles
- Young age, low BMI, higher does of gonadotropins uses, high levels of serum E2, previous episode of OHSS
What are the two steps in Ovulation induction?
- Follicular stimulation using combined FSH + LH or clomiphene is followed by:
- hCG to simulate the LH surge:
- induces follicular maturation
- Follicle aspiration or ovulation if desired
What drug is isolated from urine of pregnant women or recombinant form (Choriogonadotropin α), binds to LH/CGR (so it has LH-like induction of ovulation and stimulates estrogen primed follicle to induce meiotic resumption of oocytes, and is used following follicle stimulation by clomiphene or gonadotropins?
hCG (Human Chorionic Gonadotropin)
What is the MOA of Leuprolide?
Synthetic GnRH (i.e. GnRH agonist)
What occurs with nonpulsatile administration of Leuprolide?
Suppresses FSH & LH (but after an initial transient rise)
Used to shut down HPO axis or to stimulate follicle production when paired with a FSH/LH or chlomiphene
Used for reducing symptoms (including bleeding) of uterine fibroids
Used for controlling hormone dependent prostate and breast cancers
What occurs with pulsatile administration of Leuprolide?
Results in release of FSH and LH
Used for inducing follicle development
Which two drugs are competitive antagonists of GnRH that suppress gonadotropin release and are used in fertility to prevent endogenous LH surge while promoting folliculogenesis with exogenous gonadotropins, in prostate and breast cancer therapy to inhibit steroid production, and also in benign uterine diseases (e.g., fibroids)?
Ganirelix and Cetrorelix
Do not see transient increase in FSH & LH as with GnRH agonists
What is the most important natural estrogen?
17-beta Estradiol = principal natural hormone
- readily absorbed in tissues
- 1st pass metabolism limits oral effectiveness
What are the effects of Estrogen?
Development, growth, and maintenance of sex accessory tissue
Skeletal growth and development of body shape
Key regulator of the hypothalamo-pituitary ovarian axis and therefore in maintaining the menstrual cycle
Metabolic effects => Sodium and water retention and Increase in HDL and decrease in LDL
