USMLE Step 1 First Aid Reproductive Pharmacology – Complete Exam Study Guide 2026/2027 with Verified Answers | Newest Version. A+

USMLE Step 1 First Aid Reproductive
Pharmacology
Leuprolide -- MOA

GnRH analog --

Agonist with pulsatile fashion

Antagonist with continuous use (downregulates GnRH receptor in pituitary --> Decrease FSH
and LH)

Leuprolide -- Use

Infertility (pulsatile)

Prostate cancer (continous with flutamide)

Uterine fibroids (continuous)

Precocious puberty (continuous)

FIRST LINE for women w/ severe or refractory endometriosis-related pain (continuous)
(inhibits GnrH --> decrease FSH/LH --> decrease estrogen. the endometrium needs estrogen to
grow (proliferate), so decrease in estrogen --> shrinking of abnormal endometrial tissue)

Leuprolide -- Toxicity

Nausea
Vomiting

Osteoporosis
Pseudomenopause (night sweats, hot flashes)

Estrogens-- Names

Ethinyl estradiol, DES, Mestranol

,Estrogens-- MOA

Bind estrogen receptors

Estrogens-- Use

1) Hypogonadism
2) Ovarian failure
3) Menstrual abnormalities
4) Hormone replacement therapy (post menopausal women)
5) Androgen dependent prostate cancer (men)

Estrogens-- AE

1) Endometrial cancer (when given w/o progesterone)
2) Bleeding in postmenopausal women
3) Clear cell adenocarcinoma of vagina (DES in utero)
4) Thrombi
5) Pancreatitis
6) Cholestatic jaundice
7) Ischemic colitis
8) Invasive breast and ovarian cancer

Contraindication for estrogen therapy

ER+ breast cancer
DVT history

Name the SERMs

Clomiphene
Tamoxifen
Raloxifene

Selective Estrogen Receptor Modulators-- SERMs: Clomiphene-- MOA

Antagonist at estrogen receptors in hypothalamus
Prevent normal feedback inhibition--> increases AP release of LH and FSH--> ovulation

Selective Estrogen Receptor Modulators-- SERMs: Clomiphene-- Use

Treats anovulation in PCOS

Selective Estrogen Receptor Modulators-- SERMs: Clomiphene-- Toxicity

,Hot flashes
Ovarian enlargement
Multiple simultaneous pregnancies
Visual disturbances

Selective Estrogen Receptor Modulators-- SERMs: Tamoxifen-- MOA

Antagonist on breast tissue
Agonist-- bone, uterus

Selective Estrogen Receptor Modulators-- SERMs: Tamoxifen-- Use

Treat and prevent recurrence of ER/PR+ breast cancer

Selective Estrogen Receptor Modulators-- SERMs: Tamoxifen-- Toxicity

Endometrial cancer, thromboembolism

Selective Estrogen Receptor Modulators-- SERMs: Raloxifene-- MOA

Antagonist at breast/uterus
Agonist on bone-- decrease resorption

Selective Estrogen Receptor Modulators-- SERMs: Raloxifene-- Use

Osteoporosis

Selective Estrogen Receptor Modulators-- SERMs: Raloxifene-- Toxicity

Thromboembolism

(no increase in endometrial cancer, unlike tamoxifen)

Name the aromatase inhibitors

Anastrozole
Letrozole
Exemestane

Anastrozole/Letrozole/Exemestane-- MOA/CU/AE

Aromatase inhibitor -- inhibit peripheral conversion of androgens to estrogen

postmenopausal women with ER+ breast cancer

AE =

, 1) stevens-johnson syndrome
2) cataracts
3) increased risk of endometrial cancer
4) thrombosis
5) leukopenia
6) osteoporosis

Hormone Replacement Therapy-- Use

1) Prevention or relief of menopausal symptoms-- hot flashes, vaginal atrophy

2) Osteoporosis-- increase estrogen, decrease osteoclast activity

Hormone Replacement Therapy-- Risk

Unopposed estrogen-- increase endometrial cancer (Progesterone is added to decrease risk?)

Increased CV risk

Name the progestins

Levonorgestrel
Medroxyprogesterone
Etonogestrel
Norethindrone
Megestrol
(+ many others when combined with estrogen)

Progestins-- MOA

Bind progesterone receptors-- decrease growth and increase vascularization of endometrium,
thicken cervical mucus

Progestin-- Use

Progestins are contraceptives (pill, IUD, implant, depot)

Treatment of endometrial cancer

Abnormal uterine bleeding

Name the antiprogestins