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
What are the three clinical uses of estrogens?
- Oral contraceptives (Usually in combination with Progestins) => Interfere with LH surge and ovulation
- Hormone Replacement Therapy (usually with progesterone)
- Dysmenorrhea
What addition to 17-beta Estradiol makes it orally active?
addition of an ethinyl group at C-17 (becomes ethinyl estradiol) reduces metabolism => hormonal contraceptive estrogen
How are estrogens metabolized?
Metabolism by liver => metabolites conjugated
Conjugates excreted in kidney or bile
What is circulating estradiol bound to?
steroid hormone binding globulin (SHBG)
Estrogens increase synthesis of SHBG
(Androgens decrease synthesis of SHBG)
What Selective Estrogen Receptor Modulator (SERM) is used for ovulatory dysfunctionin patients who are:
- Not pregnant and with normal liver function
- Polycystic ovarian syndrome but not other causes of enlarged ovaries
- Amenorrhea
clomiphene citrate
What Selective Estrogen Receptor Modulator (SERM) is an estrogen antagonist in some tissues (Breast, Vasculature) and an agonist in some tissues (Uterus, bone, lipoproteins)?
Tamoxifen
What is the one drug that is a PURE estrogen antagonist/SERD (blocks receptor binding & down regulates receptor in all tissues) that is used for estrogen receptor positive breast cancer treatment?
Fulvestrant
What are the four SERMs that we need to know?
clomiphene citrate
Raloxifene
Toremifene
Fulvestrant
What drug class prevents conversion of testosterone to estradiol and can be steroidal/nonsteroidal and reversible/nonreversible?
Aromatase Inhibitors
What are the two nonsteroidal and reversible aromatase inhibitors?
Anastrozole and Letrozole
What is the Aromatase Inhibitor that is steroidal and nonreversible?
Exemestane
What are the effects/actions of Progesterone?
Development and maintenance of secretory endometrium
Promotes uterine relaxation during pregnancy
Withdrawal during late pregnancy is part of parturition
Prepares breast for lactation
Two receptors, PR-A and PR-B, one gene
What are the clinical uses of Progesterone treatment?
Oral contraceptives
Alone or with estrogens
Hormone Replacement Therapy
Alone or with estrogens
Treatment of Dysmenorrhea
Luteal Support for implantation and pregnancy
As a Plan B to interfere with ovulation following unprotected sexual intercourse
