FERTILITY AND REPRODUCTION MEDS

• -Present in males and females-diff. amounts
• -Estrogens
• -Androgens (Testosterone)
• -Progestins (Progesterone)

• -Development stimulated by LH
• -Produced by:
•       -Ovaries in females in small quantities
•       -Testes in males in larger quantities

• Estrogens- produced ovary and placenta, testes, and adrenal cortex.
• Progesterone- produced in the adrenal glands, the gonads (specifically after ovulation in the CORPUS LUTEUM), the brain, and during pregnancy the PLACENTA.

• -Begins with menstruation (3-6 days)
• -Hypothalmus-
•      -Releases gonadotropin-releasing hormone (GnRH) to act on  the anterior pituitary which stimulates FSH.
• -Follicular phase-
•      -FSH is released (ant. pit)
•      -Estrogen secretion dominates and   increases.
•      -Causes endometrium to proliferate
•      -Stimulates ovulation at midcycle
• Luteal phase-
•      -Surge of LH started the luteal phase (ant. pit). LH SURGE TRIGGERS OVULATION!!!!!!
•      -Triggers ovulation
•      -LH surge causes Graffian follicle to swelland rupture resulting in ovulation
•      -Graffian follicle turns into the corpus luteum
•      -Preparation of uterus for pregnancy
•      -Secretes estrogen and progesterone
•      -If no pregnancy, corpus luteum decreases estrogen and progesterone and you menstrate.
•      -If pregnancy, placenta secretes human chorionic gonadotropin.
• -FSH AND LH ARE HORMONES FROM THE ANTERIOR PITUITARY!!!!!

• -Sensitize myometrium (in uterus) to oxytocin at parturition labor
• -Stimulates secondary sex characteristics
• -Affect mood andemotions
• -Affect body feminine body fat distribution
• -Enhances blood coagulation
• -Inhibits bone resorption (STRENGTHENS THE BONES)
• -Mild mineralocorticoid properties (SALT AND WATER RETENTION)
• -Increase HDL (CHOLESTEROL LEVELS DECREASE)

• -Increase basal body Temperature at ovulation and luteal phase
• -Affects emotional state
• -Mild mineralcorticoid properties

• -Development of 2ndary sex characteristics in  males
• -Growth of larynx, thickening of vocal cords
• -Stimulates growth of penis, scrotum, seminal vesicle and prostate gland
• -Stimulates and maintains sexual function
• -Increases in lean body mass
• -Stimulates skeletal growth
• -Accelerate epiphyseal closure
• -Incrases sebaceous gland activity and sebum production which produces acne
• -Incrases erythropoietin in the kidneys
• -Decreases HDL cholesterol
• -Mild mineralcorticoid properties

• 1.  Natural-
• -Estradiol
• -Conjugated estrogens (OBTAINED FROM THE URINE OF A PREGNANT MARE (HORSE)
• 2.  Synthetic
• -Ethinyl estradiol
• -Mestranol

• -Well absorbed from GI tract
• -Natural estrogens rapidly metabolized in the liver
• -Synthetic estrogens are degraded (metabolized) less rapidly
• -Most estrogens are readily absorbed from skin and MM, and vaginally
• -Enterohepatic cycling- (ESTROGEN GOES TO LIVER AND IS BROKEN DOWN THEN GOES TO GI AND BACTERIA REACTIVATES ESTROGEN MOLECULES AND THEY ARE REASBSORBED BACK INTO THE SYSTEM)accounts for drug interactions, broad-spectrum antibiotic use alters bowel flora and rend OC ineffective.
• -Depends on the sexual maturity of the recipient
• -Before puberty- Stimulate development of 2ndary sex characteristics
• -Adult female- given cycliacally induce artificial menstrual cycle
• -Used for contraception
• -MUST BE GIVEN WITH PROGESTERONE DUE TO ENDOMETRIAL HYPERPLASIA
• -At or after menopause- prevent s/s of menopause, MUST BE GIVEN WITH PROGESTERONE DUE TO ENDOMETRIAL HYPERPLASIA if patient has an intact uterus.
• -Protects against Osteoporosis- but shouldn't be prescribed for this alone use Fosamax.
• -THE ONLY TIME ESTROGEN CAN BE GIVEN ALONE IS IF PATIENT HAS NO UTERUS!!!

• 1.  Hormone replacement therapy- Estrogen/Progesertone preapartions
• 2.  Oral contraception/acne/dysmenorrhea-
• Estrogen/Progesterone prepartions
• Progesterone preparations
• 3.  Estrogen receptor antagonist
• -hormonal therapy for breast cancer
• 4.  Testosterone and adrogens
• -replacement therapy- in men with decreased levels of testosterone.

• -breast tenderness
• -h/a
• -edema (NA AND H20 RETENTION)
• -n/v
• -anorexia
• -changes in libido
• -HTN (NA AND H20 RETENTION)
• -thromboembolic disorders
• -gallbladder disease
• -MONITOR PTS BP FREQUENTLY.

• -Replacement therapy for -
• Primary ovarian failure (Turner's syndrome)- Estrogen will stimulate sexual characteristics.
• Secondary ovarian failure (menopause) for flushing, vaginal dryness and to preserve bone loss
• Contraception
• Male Cancer- decreases the aggressiveness of the cancer.
• CONTRAINDICATED IN PREGNANCY, UTERINE FIBROIDS, HEPATIC DISEASE, ENDOMETRIOSIS, THROMBOEMBOLIC DISEASE, AND HYPERCALCEMIA.

• -Suppress ovarian function
• -Contraception
• -Dysmenorrhe
• -Endometriosis
• -Uterine bleeding
• -Mifepristone-termination  of pregnancy
• -Cancers- breast, endometrial, and renal.

• -Megestrol
• -Hydroxyprogesterone caproate
• -Medoxyprogesterone acetate
• Synthetic
• BIRTH CONTROL PILL NAMES TO RECOGNIZE-
• -19 norprogestines-
•      -Estranes- Norethindrone and Norethynodrel
•      -Gonanes- Levonorgesterol, Desogestrel, and norgestimate.

• ESTROGENS-
• -must be combinationwith progesterone
• -giving estrogen alone to women who have not had a hysterectomy increases risk of endometrial cancer
• -relieves vasomotor symptoms of meopause such as dizziness, h/a, tachycardia, palpitations, night sweats, atrophic vaginitis
• -benefits in Osteoporsis and CV disease
• -decreases levels of LDL and lipoproeinemia, increases levels of HDL - PROGESTERONE IS THE OPPOSITE!

• 1.  Oral preparations-
•      -First pass metabolism
•      -Hypertension
•      -Thromboembolic d/o
•      -gall bladder disease
•      -induction of drug-metabolizing enzymes-metabolize other drugs faster..which we don't want...ex. seizure med.
•      -uterine bleeding
•      -increased r/f breast cancer-mild
• 2.  Transdermal estradiol preparation-
•      -physiologic levels of estradiol
•      -consistent blood levels
•      -Long duration of action
•      -Convenience
•      -Apply 1-2 x per week
•      -Mild skin reactions
• 3.  Vaginal administration- cream used primarily for vaginal s/s of menopause
• 4.  Vaginal ring- releases estrogen for 3 months- helps atrophic vaginitis and releives menopause s/s

- It stops the pituitary gland from producing LH and FSH which causes a decreased level of estrogen.  It also supports the uterine ling to prevent BREAK THROUGH bleeding mid-cycle

• -cyclic or continuous replacement
• -estrogen is for 25 days then progesterone starts on day 10 per cycle
• -may or maynot have rx for 5-6 for menses
• -progesterone suppresses risk of endometrial hyperplasia and r/f endometrial cancer.

• -contain femail hormones
• -prevent ovulation
• -estrogen and progestin or progestin only
• -progestin- long acting subdermal implants and Depot IM injections.

• -Monophasic
• -same amt of progestin and estrogen throughout cycle
• -biphasic and triphasic- mimic menstrual cycle- incrased amount after first 1/3 cycle

• -prevent midcycle FSH/LH surge (big peak)
• -stimulates ovualtion
• -Indications- 21 cycle day pilss, start day 5 of menstural cycle or "Sunday start", acne, dysmenorrhea (is a result of increase in uterine prostaglandins which cause ischemia from small arteries in uterus at time of menstration.
• -NSAIDS- prohibit prostaglandin synthesis

• -risk of stroke
• -MI, DVT
• -thromoembolic complicaitons
• -smokeer over age 35- do not give!
• -caution- in GB disease, thromboembolic disease, and h/o MI or CAD
• -contraindicated in active liver disease (where they are metabolized), breast cancer, or CA of reproductive tract
• -increased r/f ovarian and endometrial ca
• -increased r/f breast ca

• -acne better or worse
• -hisuitism
• -increased libido
• -oily skin
• -DVT
• -nausea
• -Mastalgia- painful breasts
• -migraines better or worse
• -no menses- amenorrhea
• -weight gain

• -"The morning after pill- plan B"
• -estrogen and progesterone
• -not taking other contraceptives!
• -taken 72 hours within intercourse
• -followed by two doses 12 hours later
• -inhibit transport of ova in fallopian tubes and later endometrium to prevent implantation of fertilized ovum
• -adverse effects- N/V, h/a, dizziness, leg cramps, abdominal cramps
• -comes with a pre-packaged uterine pregnancy test.

• ACHES
• A- abdominal pain (GB disease)
• C- chest pain (MI)
• H- headache
• E- eye problems
• S- severe leg pain (DVT)
• STOP TAKING IF ANY OCCUR!!!!

• -drugs which increase heaptic metabolism of OC
• -increases possiblitly of contraceptive failure- metabolized out of the system
• -Phenytoin, barbituates, carbamazepine, antibiotics alter intestinal flora, warfarin, cyclosporine, anti-depressants, glucosteroids, increased hepatotoxic effects with dantrolene.

• -work against egg implantation  in the uterus
• -blunts LH surge that produces ovulation
• -thickens and decreases cervical mucous
• -create thin, atrophic endometrium hostile to implantation of blastocyt
• -IUD- localized effects on the endometrium
• -higher failure rates with progestin-only contraceptives
• -frequent spotting
• -amenorrhea
• -increased r/f ectopic pregnancy
• -Norethindrone (minipills", Medroxyprogesterone acetate- depo shot, progesterone IUD's- release a small amount locally.

AT THE SAME TIME EACH DAY TO DECREASE THE R/F BREAK THROUGH BLEEDING.

• -Have tissue specific action- work against the estrogen in  the body- meds treat infertility.
• -med has to bind to estrogen receptors to be effective if blocked can't connect
• -FOOL the body into thinking not enough estrogen so FSH and LH are increased to stimulate ovaries for ovulation
• -exert tissues-specific antagonist or partial agonist effects
• 1. Clomiphene
• 2.  Raloxifene
• 3.  Tamoxifen

• -taken day 5 of cycle- when ovulation occurs
• -estrogen agonist and moderate estrogen antagonist
• -indications- anovulatory infertility
• -antagonizes estrogen receptors in hypothalamic-pituitary-ovarian axis- all of these need to be secreting normally for med to work- can't increase them if they are not functioning normally
• -blocks estrogen negative feedback and incrases FSH and LH secretion helps ovarin follicle development and ovulation.
• -anovulatory d/o; infertility
• -inhibits GnRH by inhibiting neg feedbck effects of endogenous estrogen
• -less successful in women with decreased estrogen levels
• -unlikely to benefit women with FSH levals at or above 40.
• -taken days 5-10 mesntrual cycle
• -ovulation expected 5-10 days after last dose of clomiphene
• -adverse effects- MULTIPLE BIRTHS

• -breast tissue-estrogen receptor antagonist
• -TREATS BREAST CANCER
• -adverse effects- N/V, hot flashes, vaginal bleeding, menstrual irregularities
• -possibly stimulates proliferation of endometrial cells-endometrial CA
• -possibly stimulates proliferation of endometrial cells- endometrial CA

• -selective estrogen receptor modulator (SERM)
• -TREATS OSTEOPOROSIS IN MENOPAUSAL WOMEN.
• -but allows estrogen-like effects on bone and lipid metabolims- good for bones
• -antagonizes effects of estrogen on breast tissue
• -estrogen antagonist in uterine tissue
• -

• 1.  Mifepristone-
• -an antagonist of progesterone receptors
• -sentisizes uterus to action of prostaglandins
• -inhibits ovulation
• -alternative to surgical termination of pregnancy before 9 WEEKS of pregnancy

• TREATS-
• 1.  Hypogonadism- primary testicular failure
• 2.  Hypopituitarism- given with growth hormone to obtain maximal effect on skeletal growth.  Occassionally used in given in GYN d/o of endometrial bleeding and osteoporosis.

• -first-pass metabolism extensive- if taken orally and some is reabsorbed so give IM or TD.
• -given parenterally or transdermally
• -ONLY ORAL ONE IS METHYLTESTERONE- IF NO OTHER CHOICE- RESISTANT TO HEPATIC METABOLISM BUT CAN CAUSE HEPATIC DAMAGE AND LIVER FAILURE WITH PROLONGED TX.

• -infertility
• -if given  for a long period the normal testosterone in your body will lose its effect
• -salt and water retention with edema
• -CA of liver
• -impairs growth in children
• -acne
• -masulinization in girls

• ANABOLIC STEROIDS-
• 1.  Fluoxymesterone
• 2.  Oxandrolone
• -3 x more potent than testosterone
• -promote wt gain and muslce development
• -what athletes use- ABUSE
• -counteract protein metabolism
• -treat breast CA
• -controlled substances
• -increase body mass, strength, physical performance
• -adverse eff-hepatic dysfunction, jaundice, aggressiveness, psychotic symptoms, acne, decreased testicular size and function, impotence
• -women- masculinization, hirsuitism, deep vouce, menstral irregularities
• -athlete abuse

• -testosterone derivative
• -weak androgenic and progestational activity
• -po
• -half life 5 hours: excreted in urine
• -acts on pituitary gland to reduce secretion of GnRH, FSH, and LH, which leads to decreased estrogen production.
• -RX- endometriosis, fibrocystic breast disease, gynecomastia, hereditary angioedema
• -adverse eff.- mild hirsuitism, oily skin and acne, menstural irregulatities, hypercholsterolemia, hepatotoxicity, thromboembolic event, TERATOGENIC
• -decreases growth rate of abnormal breast tissue

• -compete with estrogens and progesterones- inhibit gonadotropin secretion and/or compete with androgens in target organs
• 1.  Cyproterone-
• -androgen receptor antagonist
• -adjunct in rx of PROSTATIC CA
• -RX of precociuous puberty in males
• -RX of masculinization and acne in women
• 2.  Gonadotropin-releasing hormone analogues-
• -decrease LH secretion which decreases testosterone synthesis by the testes
• -Leuprolide- prostate cancer
• -prolongs progression-free period and length of survival of men with advanced prostate cancer
• 3.  Flutamide-
• -androgen receptor antagonists
• -competes with testosterone for androgen receptor
• -RX of prostate CA
• -adverse eff- mild gynecomastia, mild reversible hepatic toxicity
• 4.  Finasteride-
• -has affinity for androgen receptors in prostate gland
• RX- BPH, and baldness

• KETOCONAZOLE-
• -inhibit synthesis of testosterone
• -antifungal drug
• -inhibits CP450 enzymes inchluding those involved in steroidgenesis
• -inhibits fungal infections and testosterone sythesis
• -causes gynecomastia
• -RX of prostate CA and Cushings syndrome- reduces steroid synthesis in the body.