Lecture 23 and 24 - Pharm of Sex Steroids

Question 1

If estrogen drugs are given to a patient with a Uterus, it is ALWAYS given with a _______. One exception to that rule is women receiving VERY low dose Estrogen therapy for ______ atrophy –> in this case, the Estrogen can be given by itself.

Answer 1

Progestin

Vaginal atrophy

Question 2

Remember that _______ is a protein produced by Osteoblasts that binds RANKL and blocks its interaction with RANK –> prevents Osteoclast maturation. And remember _____ (hormones) stimulates its production.

Answer 2

Osteoprotegerin (OPG)

Estrogen

Question 3

Progesterone levels begin to rise at the beginning of the _____ phase. Keep in mind progestins halt proliferation induced by estrogens.

What happens to the endometrial lining in the absence of Progesterone?

Answer 3

Ovulatory

It is shed via menses.

Question 4

Postmenopausal women should only receive Estrogen replacement therapy if their menopause symptoms are severe, and it should only be given for ___-___ years. The exception to that is women at high risk for developing _____ –> they can be given replacement therapy indefinitely.

Answer 4

1-2years

Osteoporosis

Question 5

Combination oral contraceptives use an Estrogen and a Progestin, but they do not use E2 and Progesterone. Thus, they act to lower FSH, LH, Progesterone, and E2.

What effect does this have on ovulation, endometrial thickening, and formation of a cervical mucus plug?

Answer 5

This prevents ovulation (no LH surge or follicle maturation), renders the endometrium inappropriate for implantation (bc low progesterone), and it forms a smaller mucus plug than would otherwise be present with progesterone.

Question 6

In some cases, bc it drastically lowers E2, oral contraceptives can be used to treat _______.

Answer 6

Endometriosis

Question 7

Female horses (mares) excrete a ton of conjugated _______, and this is how they are obtained for oral contraceptives.

Answer 7

Conjugated Estrogens

Question 8

______ _____ and ______ are the synthetic forms of Estrogen in 82 of the 83 oral contraceptive formulations in the US. On ingestion, ______ is converted to _____ _____ in the liver, so this is the active ingredient essentially in those 82 formulations –> it is a potent inducer of E2 negative feedback at the Hypothalamus.

Answer 8

Ethinyl Estradiol

Mestranol

Mestranol

Ethinyl Estradiol

Question 9

According to the CDC, all formulations of oral contraceptives have a ____% success rate.

Answer 9

91%

Question 10

Diethylstilbesterol is a synthetic ________ (steroidal or non-steroidal?) estrogen. How does its half-life compare to the other estrogens?

Answer 10

Non-steroidal –> so longer half-life.

Question 11

Fluid retention is one of the moderate-severe side effects of exogenous estrogen. Estrogen increases the production of _______ in the liver –> converted to ______ –> stimulates Aldosterone –> added potential risk of HTN.

____ ____ disease, clotting disorders, myocardial infarction, and _______ are also moderate-severe risks of exogenous estrogen.

Keep in mind that risk for ______ ______ in premenopausal women is increased ONLY if they have other predisposing risk factors.

Answer 11

Angiotensinogen

Angiotensin II

Gall Bladder disease, Clotting disorders (Estrogen promotes production of clotting factors in liver), myocardial infarction, and Teratogenicity (if taken in the 3rd trimester)

Myocardial infarction

Question 12

Unopposed Estrogens increase the risk for _______ cancer, but combination Estrogen+Progestin actually decreases this risk. The same is true for ______ cancer (including patients with BRCA1 and 2 mutations.). However, the evidence for risk of ______ cancer is inconclusive.

Answer 12

Endometrial cancer (this should make sense since progesterone is necessary to stop endometrial proliferation induced by estrogen)

Ovarian cancer

Breast cancer

Question 13

There is increased risk for ______ adenocarcinoma in females born of mothers who took estrogens DURING the pregnancy.

Answer 13

Vaginal Adenocarcinoma

Question 14

Estrogens also increase the risk for ____ cancer, though this is mostly attributed to HPV infection.

Answer 14

Cervical

Question 15

Oral contraceptives are safer than pregnancy and childbirth in smokers up to about age ______, and in non-smokers up to about age ______. Thus, they would not be recommended to women of these respective ages and smoking status.

Answer 15

35

40

Question 16

Griseofulvin and Rifampin both increase activity of CYP450 3A4 which metabolizes ________ (the active ingredient in 82/83 oral contraceptives). This will lower the tissue levels of the contraceptive and increase risk of pregnancy.

Answer 16

Ethinyl Estradiol

Question 17

________ is a SERM (Selective Estrogen Receptor Modulator) used in the treatment of Estrogen-dependent breast cancer. It acts as an antagonist at these receptors in breast tissue, BUT it acts as a partial agonist in _______ tissue –> after about _____ years, this risk outweighs the benefit.

Answer 17

Tamoxifen

Endometrial

5 years

Question 18

_______ and ______ are SERMs that were first used for Osteoporosis treatment (enhance production of OPG by osteoblast).

Which one is antagonistic to estrogen receptors in both Breast and Endometrial tissues, and which one is only antagonistic in Endometrial tissues (and thus given in combo with Estrogen for post-menopausal women –> keep in mind this is the other exception to always giving opposed Estrogen to women with uteruses!)?

Answer 18

Raloxifene

Bazedoxifene

Raloxifene –> antagonistic in both Breast and Endometrium

Bazedoxifen –> just endometrium and is the other exception.

Question 19

______ is a SERM given as an infertility treatment in women with low E2. It blocks the negative feedback of E2 at the Hypothalamus –> more GnRH –> more FSH and LH.

Answer 19

Clomiphene

Question 20

SERDs (Selective Estrogen Receptor Down-regulators) bind to the estrogen receptor in the cytoplasm and prevent their entry into the nucleus. ______ is one such drug and is used in the treatment of estrogen-dependent breast cancer. It is typically used in women who don’t respond well to _____ or _____.

Answer 20

Fulvestrant

Tamoxifen

Raloxifene

Question 21

Letrozole is an ______ inihibtor, and it is only given to post-menopausal women bc they no longer have gonadal production of E2. If given to pre-menopausal –> decreased E2 neg feedback –> increased GnRH + FSH + LH.

It is used to treat estrogen-dependent _____ cancer.

Answer 21

Aromatase

Breast cancer

Question 22

What is the big difference between Progestin only oral contraceptives and Estrogen+Progestin combos?

Answer 22

Progestin onlys have much higher risk of pregnancy with missed dose or inconsistent timing of dose.

Question 23

A depo contraceptive is a ______-based contraceptive in a propylene glycol form that’s injected into the muscle layer and remains active for up to 4 months.

Implanted contraceptives, Plan B, and intrauterine devices (>99% effective) are also _____-based.

Answer 23

Progestin

Progestin

Question 24

Bc Estrogens tend to decrease milk production, ______-based contraceptives are preferred after birth to allow breastfeeding.

Answer 24

Progestin

Question 25

Levonorgestrel is a synthetic progesterone and is the medication in ______ ___.

Answer 25

Plan B

Question 26

While Medroxy-progesterone has _______ effects, Megestrol (another progestin) has anti-______ effects.

The above two AND Progesterone all have anti-______ effects at high doses.

Answer 26

Androgenic

Anti-androgenic

Anti-estrogenic

Question 27

________ is an antagonist of Progestin, and it is used within the first 10 weeks as a medication for abortion.

Answer 27

Mifepristone

Question 28

Sometimes, Androgens can be given therapeutically to women for ________-dependent disorders, including Endometriosis and Fibrocystic Breast disease. The Androgens cause neg feedback in the Hypothalamus –> less GnRH –> less E2.

Answer 28

Estrogen-dependent

Question 29

______ is a very weak synthetic androgen that’s used to treat endometriosis.

Answer 29

Danazol

Question 30

________ is a drug that inhibits 5alpha-reductase, the enzyme that converts Testosterone to DHT (the full agonist of the androgen receptor). It is used in the treatment of _____ cancer and benign ______ hyperplasia.

Answer 30

Finasteride

Prostate

Prostatic

Question 31

______ is an antagonist of the androgen receptor, itself. It is also used to treat prostate cancer and benign prostatic hyperplasia.

Answer 31

Flutamide

Question 32

_______ at large doses antagonizes the androgen receptor and also reduces the production of testosterone. It was given as a diuretic, but is now used in feminization treatments for transgender men who have not had and orchiectomy.

Answer 32

Spironolactone