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Flashcards in Estrogens and Progestins Deck (81):
1

Where are estrogens synthesized?

Ovary, liver (from estriol), and peripheral tissue (from androgens)

2

Where are progestins synthesized?

Ovary, testis, adrenal from circulating cholesterol
Placenta during pregnancy

3

Where are androgens synthesized?

Testis (95%)
Adrenal glands (5%)

4

What is the more estrogenic/active estrogen?

Estradiol 17B (E2)

5

What are the natural estrogens?

Estradiol 17B (E2)
Estrone (E1)
Estriol (E3)

6

What are the synthetic steroidal estrogens?

Ethinyl estradiol
Mestranol
Quinestrol

7

What are the synthetic non-steroidal estrogens?

Diethylstilbestrol (DES)
Chlorotrianisene
Methallenestril

8

Which cells synthesize and secrete LH and FSH?

Gonadotrophs

9

Action of LH and FSH in females

LH stimulates theca cells to synthesize androgen which is aromatized to estrone (E1) and estradiol (E2) in granulosa cells via FSH action

10

Action of LH and FSH in males

LH stimulates testicular Leydig cells to increase the synthesis of testosterone, which diffuses to neighboring sertoli cells

11

Which cells synthesize and secrete Inhibin A, Inhibin B, and Activin

Sertoli cells
Granulosa cells

12

What is the action of inhibin on the gonadotrophs?

inhibits the release of FSH

13

what is the action of activin on gonadotrophs?

stimulates FSH release

14

What is the enzyme that converts testosterone to estrogen?

aromatase

15

Reproductive actions of estrogen

Growth, development, structural maintenance of primary and secondary female sex characteristics
Changes at puberty
Regulation of menstrual cycle
Growth of uterine endometrium
Secretion of thin cervical mucus

16

Metabolic actions of estrogen

Increase HDL, decrease LDL
Increase cholesterol saturation of bile
Increase BP via renin
Promote thrombosis (clotting factors)
Decrease bone reabsorption
Increase liver protein synthesis

17

CNS actions of estrogen

Positive effects on mood
Positive effects on cognition and memory

18

Major clinical uses of estrogens

Oral contraceptives
HRT during menopause
HRT for delayed puberty or hypogonadism in women
Rx of perimenopause, dysmenorrhea, oligomenorrhea, delayed puberty
Rx of acne

19

Estrogen preparations

Conjugated estrogens
Estradiol
Estradiol transdermal
Ethinyl estradiol (syn steroid)
Diethylstilnestrol (DES) (syn non-steroid)

20

Estrogen indictions

Vasomotor symptoms of menopause (flushing)
Vulvar and vaginal atrophy
Female hypoestrogenism secondary to hypogonadism castration or primary ovarian failure
Retard bone loss/ osteoporosis

21

Estrogen side effects

Nausea and vomiting
Edema
Headache
Breast tenderness
Venous thrombosis
Breakthrough bleeding
Estrogen alone (w/o progesterone) causes endometrial hyperplasia and possible endometrial carcinoma
Increase adenocarcinoma of vagina (DES)

22

Estrogen contraindications

Breast and endometrial cancers
Cerebral vascular coronary artery disease
Benign or malignant liver tumors
Severe hypertension
Pregnancy
Female smokers over 35
Thrombotic disorders

23

Selective Estrogen Receptor Modulators (SERMs)

Tamoxifen
Clomiphene
Raloxifene

24

Tamoxifen (SERMS) Indication

Prevention, palliative, adjuvant therapy for breast cancer (ER+)
pre or post menopausal

25

Tamoxifen (SERMS) MOA

Estrogen receptor antagonist in the breast tissue, partial agonist in the endometrium and bone

26

Tamoxifen (SERMS) side effects

Malignant neoplasm of endometrium
Cataract
Pulmonary embolism
Hot flashes
Abnormal menstruation
Vaginal discharge

27

Tamoxifen (SERMS) contraindication

Deep vein thrombosis or pulmonary embolism
Pregnancy

28

Tamoxifen and endometrial cancer

Tamoxifen is associated with 4-6 fold increase in incidence of endometrial cancer
Administered for no more than 5 years to minimize risk

29

Clomiphene (SERMS) indication

Female infertility due to ovulatory disorder

30

Clomiphene (SERMS) MOA

Estrogen receptor antagonist in hypothalamus and pituitary gland, partial agonist in ovaries

31

Clomiphene (SERMS) Side effect

Thromboembolism
Ovarian cysts and hypertrophy
Flushing and vasomotor symptoms
Abdominal discomfort

32

Clomiphene (SERMS) contraindications

Pregnancy
Thyroid or adrenal dysfunction
Liver disease
Endometrial carcinoma
Ovarian cysts
Intracranial lesion

33

Benefit of Clomiphene over exogenous FSH

Clomiphene is rarely associated with the ovarian hyperstimulation syndrome

34

Raloxifene (SERMS) Indication

Osteoporosis prevention and treatment

35

Raloxifene (SERMS) MOA

Estrogen receptor agonist in the bone and estrogen receptor antagonist in uterus and breast

36

Raloxifene (SERMS) Side Effects

Retinal vascular occlusion
Venous thromboembolism
Hot flashes
Leg cramps

37

Raloxifene (SERMS) Contraindication

Pregnancy
History or presence of venous thromboembolism

38

What is the effect of Raloxifene on invasive breast cancer?

Decreases the risk of invasive breast cancer is POSTmenopausal women with osteoporosis

39

Estrogen receptor antagonists

Fulvestrant

40

Fulvestrant indications

Rx of estrogen receptor+ metastatic breast cancer in POST menopausal women with disease progression following anti-estrogen therapy (ex. Tamoxifen)

41

Fulvestrant MOA

Competitively inhibits estrogen binding to receptor
Estrogen receptor antagonist

42

Fulvestrant Side Effects

Nausea
Asthenia (lack of strength)
Pain
Vasodilation (hot flashes)
Headache

43

Fulvestrant contraindication

Pregnancy

44

Does fulvestrant have any agonist activity?

NO

45

What is the action of aromatase?

converts testosterone to estrogen

46

Aromatase Inhibitors

Anastrozole
Letrozole
Exemestane
Formestane

47

Aromatase Inhibitors Indications

Treatment and prevention of estrogen receptor positive breast cancer (early, locally advanced, or metastatic)

48

Anastrozole and Letrozole MOA

Competitive inhibitors of aromatase (reversible)

49

Exemestane and Formestane MOA

Irreversible inhibitors of aromatase

50

Aromatase Inhibitor side effects

OSTEOPOROTIC FRACTURES
Thromboplebitis
Hypercholesterolemia
Profuse vaginal bleeding
Peripheral edema
Rash
Nausea
Arthralgia
Bone pain
Headache
Depression
Dyspnea

51

Aromatase inhibitors vs. SERMs for the treatment of breast cancer

Aromatase inhibitors may be more effective than SERMs

52

Physiological actions of progesterone

Regulation of menstrual cycle
Induces secretory uterine endometrium (implantation)
Thick, viscous cervical mucus
Increases body temperature
Maintain pregnancy
Development of mammary gland

53

Clinical uses of progestins

Oral contraceptives
HRT in menopause
Dysmenorrhea, oligomenorrhea, endometriosis, PCOS

54

What are the three major types of oral contraceptives?

Progestin only
Combination (estrogen + progesteron)
Emergency

55

Progestin only contraceptives

Norgestrel
Norethindrone
Medroxyprogesterone acetate
Etonogestrel

56

Progestin only contraceptives indication

Contraception

57

Progestin only contraceptives MOA

Alter frequency of GnRH pulsing and and decrease anterior pituitary gland responsiveness to GnRH
Alter tubal peristalsis, endometrial receptivity, cervical mucus secretions

58

Progestin only contraceptives Side Effects

Irregular periods
Breast tenderness
Nausea
Dizziness
Headaches

59

Progestin only contraceptives Contraindications

Acute liver disease
Benign or malignant liver tumors
Known or suspected breast cancer
Pregnancy

60

Route of administration of progestin only contraceptives

Medroxyprogesterone: given parenterally every 3 months

Etonogestrel (implant): effective for 3 years

Levonogestrel (oral): emergency contraception

61

Estrogen-Progestin Combinations

Estrogens: Ethinyl estradiol, mestranol

Progestins: Norgestrel, Levonorhestrel, Norethindrone, Norethindrone acetate, Ethynodiol, Norgestimate, Gestodene, Desogestrel, Drospirenone

Combo OC:
EE+ norgestrel
EE+ drospirenone

62

Estrogen-Progestin Combinations Indications

Contraception

63

Estrogen-Progestin Combinations MOA

Suppress GnRH, LH and FSH secretion and follicular development, inhibit ovulation

Alter tubal peristalsis, endometrial receptivity and cervical mucus secretions

64

Estrogen-Progestin Combinations Side Effects

Arterial and venous thromboembolism
Pulmonary embolism
Cerebral thrombosis
Gallbladder disease
Hypertension
Hepatic neoplasm
Abnormal menstruation
Breakthrough bleeding
Breast tenderness
Bloating
Migraine
Weight change

65

Estrogen-Progestin Combinations Contraindications

Breast cancer
Endometrial cancer
Estrogen dependent neoplasms
Cerebral vascular or CAD
Cholestatic jaundice
Liver tumors
Severe hypertension
Prolonged immobilization
Pregnancy
Female smokers >35
Thrombotic disorders

66

Which progestins have the highest androgenic activity?

Norgestrel and levonorgestrel

67

Progesterone Receptor Antagonist

Mifepristone (RU-486)

68

Mifepristone (Progesterone Receptor Antagonist) Indication

Abortion (through day 49)

69

Mifepristone (Progesterone Receptor Antagonist) MOA

Inhibits progesterone binding to receptor

70

Mifepristone (Progesterone Receptor Antagonist) Side Effects

Prolonged bleeding
Bacterial infections
Sepsis
N/V/D
Cramps
Headache

71

Mifepristone (Progesterone Receptor Antagonist) Contraindications

Chronic adrenal failure
Ectopic pregnancy
Hemorrhagic disorders
Anticoagulation therapy
IUD

72

Emergency (morning after) contraception indication

Medication to prevent unwanted pregnancy after unprotected intercourse

73

Emergency (morning after) contraception

Two doses of "minipill"
0.75 mg of levonorgestrel (12 hrs)

74

Emergency (morning after) contraception MOA

Potent progestin, blocks the LH surge, disrupting normal ovulation, produces endometrial changes for implantation

75

Emergency (morning after) contraception timing

Take first dose within 72 hours of intercourse, 2nd dose 12 hours after 1st dose

76

Emergency (morning after) contraception side effects

N/V
Headache
Dizziness
Mastalgia

77

Indications for HRT

Vasomotor instability
Mood changes
Urogenital atrophy
Osteoporosis

78

HRT preparations

Conjugated equine estrogens
Micronized estradiol
Conjugated synthetic estrogens
Transdermal estrogens
Vaginal ring
Medroxyprogesterone
Micronized progesterone
Combination products (E+P)

79

Effects of HRT

Relief from vasomotor symptoms, urogenital atrophy, recurrent urinary symptoms
Relief from fatigue, depression
Maintenance of bone density

80

HRT Side Effects

E: nausea, mastalgia (breast pain), headache, fluid retention
P: weight gain, headache

81

Estrogen alone associated with ____ risk of endometrial carcinoma

5-8 x increase