Sex Hormones & Antagonists Flashcards
Estradiol (E2)
- Decrease causes GnRH release, then LH & FSH release, then making estrogen
- Most in ovulation
- 2-3% free, rest binded to SHBG
- Different during day
- Most estrogen before menopause
Estradiol decreased where?
- Ovarian insufficiency
- Turner’s syndrome
- Hypothyroidism
- PCOS
- Menopause
- Hypogonadism
Turner’s syndrome definition
Girls with one X or 2 defective chromosomes
Rubinstein-Taybi syndrome (RSTS)
- تاخیر رشد
- ناتوانی فکری
- انگشتان بزرگ
- مشکلات تغذیهای (دیسفاژی)
Estradiol increases where?
- Ovarian, testicular & adrenal tumors
- Female Precocious puberty
- Gynecomastia
- Liver cirrhosis & necrosis
Drugs that decrease E2
OCPs
Clomifen
Drugs that increase E2
- Adrenocorticosteroids
- Ampicillin
- Phenothiazines
- Tetracyclines
Estrone (E1)
- Weaker than E2
- Made from androstendione peripheral conversion & E2 metabolism
- Most estrogen after menopause
Estriol (E3)
- Main esterogen in pregnancy
- Made in adrenal, fetus liver, placenta
- Important factor for fetus health
- Checking from 28-30w, weekly
- Same hour of the day
- Screening down syndrome, natural tube defects
Estriol decrease where?
- Preterm delivery
- Pre-eclampsia
- Anemia
- Severe liver disease
Estriol increases where?
- Multiple birth
- Oxytocin use
Progesterone function
- Reconstruction & Growth of endometrium
- Preparation for egg implantation
- Low progesterone starts period
Corpus luteum
- Produces progesterone
- If no fertilization, destroyed
- If yes stays and changes into placenta
Progesterone clinical use
1- Ovulation check
2- Infertility reason check
3- Abnormal vaginal bleeding check
4- Placenta health
5- Keeping pregnancy in the beginning
6- Adrenal problems help
7- Ectopic pregnancy & miscarriage check
Testosterone (function, regulation, rhythm)
- Spermatogenesis
- Secondary sex characteristics
- In women, estrogen precursor
- Androgenic & anabolic
- Hypophysis negative feedback (LH)
- Mostly SHBG, some albumin & free
- Morning most, evening least
Testosterone increase in women (causes & problems)
Causes:
- Adrenal & Ovarian tumor
- Adrenal hyperplasia
- Trophoblastic tumor
- PCO
Problems:
- Masculinization
- Amenorrhea
- Hirsutism
Drugs that increase testosterone
- Clomifen
- Anti-seizure drugs
- Barbiturates
- Estrogens
- OCPs
Drugs that decrease testosterone
- Androgens
- Dexamethasone
- Digoxin
- Alcohol
- Steroids
- Ketoconazole
- Phenothiazines
- Spironolactone
Diseases that increase testosterone
- Hyperthyroidism
- Androgen Insensitivity Syndrome
- Encephalitis
- Hypothalamus tumor
Testosterone clinical use
1- Late or early pubert
2- Assessing in alternative therapies
3- When using anti androgens
4- Masculinizing in women
5- Checking PCOS
6- Diagnosing Androgen-making tumors
Antiestrogen types
1- Receptor antagonist (SERMs)
tamoxifen
2- Aromatase inhibitor
anastrozole
Tamoxifen
- Breast cancer
- Infertility relative to oligomenorrhea or secondary amenorrhea
Tamoxifen mechanism of action
SERMs
Selective Estrogen Receptor Modulator
Antagonistic in Breast & CNS
Agonistic in Liver & Bone
Tamoxifen pharmacokinetic
Complete absorption
Tamoxifen bio-availability
Pill & Liquid
Tamoxifen protein binding
99%
Tamoxifen liver metabolism
CYP2D6 & CYP3A4/5
- Changes into more active metabolites like:
Endoxifen, 4-hydroxy tamoxifen, n-desmethyl tamoxifen
Tamoxifen half life
5-7 days
N-desmethyl tamoxifen:
14d
Tamoxifen clearing
Stool (65%, less than 30% not conjugated)
Urine (9%)
Tamoxifen side effects
-
Cardiovascular:
Vasodilation, Hot flashes, HTN, Peripheral edema -
Skin:
Rash -
Endocrine:
Water retention, Weight loss, Amenorrhea -
GI:
Vomiting, Diarrhea -
Genitourinary:
Vaginal discharge, Irregular period, Vaginal bleed
Anastrozole use & dose
- Advanced breast cancer / in addition
- Menopausal women
- 1mg/d
Anastrozole mechanism of action
Strong Aromatase inhibitor
Aromatase system: Peripheral conversion of androgens to estrogen
Anastrozole side effects
- most common GI problems
- Hot flashes, dizziness, drowsiness, headaches
- Hair thinning, dry vagina & bleed, edema, joint & muscular pain, bone breaking, fever, weight gain
Anastrozole pharmacokinetic
- Fast & GI tract
- 2h peak plasma level
- 40% plasma proteins binding
- Consistent concentration after 7d if single daily dose
Anastrozole metabolism, clearing, half life
- Liver metabolism
- Urine clearing (metabolites)
- 50h half life
Progestin antagonists (Anti-progesterones)
- Danazol
- Mifepristone
Danazol uses
- Hip area pain
- Infertility because of endometriosis
- Fibrocystic breast disease
- Hereditary angioedema (men&women)
Danazol common side effects
- Weight gain
- Acne
- Masculinization
- Oily hair & skin
- Hair loss
- Water retention
- Hot flashes
- Irritability
- Dry vagina
- Breast size decrease
Danazol allergic side effects
- Rashes
- Itchiness
- Face & tongue swelling
- Vertigo
- Hard breathing
Danazol side effects in men
- Decrease sperm making
- Abnormal semen amount
- Less sperms & less mobility
Androgen Antagonists (Anti-testosterone)
1- 5α-Reductase Inhibitor
(Finasteride)
2- Synthesis Inhibitor
(Ketoconazole)
Finasteride contraindication
Pregnancy
(Especially boys)
OCP
Definition, examples
- Estrogen-progesterone mix
- Safe in low doses (< 50mg Ethinyl Estradiol)
Examples: - Ethinyl estradiol
- Norgesterel
OCP mechanism of action
Total, Progesterone
- Inhibition of ovulation if taken before peak of LH
Progesterone: - Endometer not suitable for implantation
- Endometrial atrophy
- Cervix mucos thickening & prevents sperms
OCP side effects
- Nausea
- NO increased sex appeal near ovulation
- لک صورت
- Change in fat & sugar metabolism
- HTN & increased clotting
OCP interactions
- Phenobarbital (gets pregnant)
- Simetidine
- Grapefruit
- Alcohol
- Phenytoin
2-6 cause overdose
OCP other effects
- Less period bleeding & pain
- Less ectopic
- Better for endometriosis
- Less hirsutism
- Less pimples
- More bone density
- Less ovarian & cervix cancer
- Less benign breast diseases
- Regulating menstruation
- Less simple ovarian cyst
Ethinyl estradiol
Type, Mechanism, pharmacokinetic, Side effects & interactions
- Estrogen receptor activation
- P450, Liver-intestine
- Moderate: Bleed in between cycles, nausea
- Severe: Thromboembolism, HTN
Norgestrel
Type, Mechanism, pharmacokinetic, Side effects & interactions
- Progestreone receptor activation
- P450, liver-intestine
- Weight gain, reversible bone density decrease (high doses)
Clomifen
- Estrogen receptor agonist to induce ovulation
- Antagonistic in pituitary to increase GnRH
