estrogens &

progestins
February 4, 2014
Sarah Adkins, PharmD, BCACP

Outline

Pharmacology basics of estrogens and progestins

Pharmacology and therapeutics

Contraception

MOA (mechanism of action)

Administration

Side effects

Drug interactions

Hormone replacement

Other

Clinical pearls

Pharmacology

Pharmacology:
estrogens
Natural estrogens
Estradiol (Estrace)

source

bioavailability

Conjugated estrogens (Premarin)

source

bioavailability

Pharmacology:
estrogens

Synthetic estrogens
Steroidal

Ethinyl estradiol (EE)

Mestranol

Non-steroidal

Diethylstilbestrol

http://www.cancer.gov/cancertopics/factsheet/
Risk/

Pharmacology:
progestins
Natural progestin

Progesterone (Prometrium, Crinone

gel)

source

PEANUT ALLERGY WITH

PROMETRIUM

Pharmacology:
progestins
Synthetic progestins

Desogestrel

Dienogest

Drospirenone

Ethynodiol
diacetate

Levonorgestrel

Medroxyprogesterone
acetate

Norethindrone acetate

Norgestimate

Norgestrel

Ulipristal mini pill.

Progestin only.

Pharmacology &
Therapeutics

Contraception:
MOA

Inhibition of pituitary gonadotropin release

(FSH & LH); involving both decreased release
of GnRH & decreased pituitary responsiveness

Inhibition of ovulation (mid-cycle surge of LH

is absent)

Other mechanisms: such as changes in

cervical mucus (making it less permeable to
sperm) & altered fallopian tube motility may
also play a role

Normal Menstrual
Cycle

contraception
effects

Combination Oral
Contraceptives

Pharmacologic
amounts of
estrogens;
pharmacologic
amounts of
progestins

Hypothalamus
GnRH
Decreased release of GnRH

(-)

Anterior lobe

Posterior lobe
Pharmacologic
amounts of
estrogens;
pharmacologic
amounts of
progestins

FSH, LH

(-)
Pituitary

FSH, LH

Decreased
pituitary
responsiveness
to GnRH & thus
decreased release
of FSH & LH

Contraception

Oral

Topical (patch)

Injection

Subcutaneous

Subdermal implant

Vaginal

IUS (Intrauterine system)

Contraception: oral

Low dose monophasic

High dose monophasic

Biphasic

Triphasic

Four phasic

Extended cycle

Continuous cycle

Emergency contraception

Contraception: oral

Emergency contraception

Levonorgestrel

Two dose regimen:

one 0.75 mg as soon as possible within 72 hours of
unprotected sexual intercourse; a second 0.75 mg tablet
should be taken 12 hours after the first dose

Single dose regimen

one 1.5 mg tablet as soon as possible within 72 hours of
unprotected sexual intercourse

Contraception: oral

Progestin only mini-pill

MOA of progestin only

Progestin-only Oral
Contraceptives
Hypothalamus
GnRH
Pharmacologic
amounts of
progestins

Decreased release of GnRH

(-)

Anterior lobe

Posterior lobe
Pharmacologic
amounts of
progestin

FSH, LH

(-)
Pituitary

FSH, LH

Decreased
pituitary
responsiveness
to GnRH & thus
decreased release
of FSH & LH

Contraception: nonoral

Topical (patch)

Ortho Evra (EE 35mcg/day & norelgestromin, active form

of norgestimate, 200mcg/day)

Injection

Depo Provera IM (medroxyprogesterone acetate 150mg)

weekly x 3 weeks and 4th week is patch free

every 3 months

Subcutaneous

Depo subQ Provera (medroxyprogesterone acetate 150mg)

every 3 months

Contraception: nonoral

Subdermal implant

Nexplanon (etonogestrel, release varies over time)

Vaginal

NuvaRing (EE 15 mcg/day & etonogestrel 0.12 mg/day)

3 years

vaginal ring inserted for 3 weeks and removed for 1 week

IUS (Intrauterine system)

Mirena (Levonorgestrel 20mcg/day) up to 5 years

Skyla (Levonorgestrel 14 mcg/day) up to 3 years

Contraceptives: side
effects

Contraceptives:
other adverse effects

Concerns related to significant adverse effects

Carbohydrate intolerance (diabetes)

Lipid effects

Depression

Gall bladder disease

Migraine (some have low does estrogen in the pill to

prevent the headaches)

Renal impairment

Contraception:
contraindications

Breast cancer or other estrogen/progestin related

neoplasm

In women with high risk of arterial or venous

thrombotic disease

> 35 years of age who smoke (US Boxed Warning)

Hepatic tumors or disease

Pregnancy

Undiagnosed abdominal uterine bleeding

Contraception: drug
interactions

Avoid concomitant use

Anastrozole (used to block estrogens in women with breast cancer.

Thyroid replacement medications

Herbal supplements

Mifepristone

Anticoagulants

Lamotrigine (Lamictal)

Bile acid sequestrants (cholestyramine resin, Questran)

Phenytoin (Dilantin)

Case #1a
A 14 year old, Emily Jones, comes to your office two
weeks post-partum. She is limited in her resources.
You:
A. give her a lecture about safe sex and contraception
B. complete her physical exam and ask how she is
feeling
C. prescribe Lo/Ovral-28 (EE 30mg/Norgestrel 0.3mg)
D. prescribe NuvaRing (EE 15mcg/day & Etonogestrel
0.12mg/day)
E. do not prescribe anything and schedule a follow up

Case #1b
You have a nice discussion with Ms. Jones about birth
control, breast feeding and post-partum depression. Ms.
Jones has decided that she will begin using birth control.
Which of the options below may be the best for Ms. Jones?
A. Jolivette (Norethindrone 0.35mg only)
B. LoSeasonique (Extended cycle, EE 20mcg &
levonorgestrel 0.1mg x 84 days)
C. Depo-Provera Inj. (Medroxyprogesterone acetate
150mg x 3 months)
D. Mirena IUS (Levonorgestrel 20mcg/day for up to 5
years)

Case #2a
25 year old, Stacey Smith, visits you at the clinic and would like to
start birth control. She has never used hormone contraceptives. She
and her partner are currently using condoms and spermicide. She is
a little nervous and would like to take something that is similar to her
normal cycle. What might be a good starting contraceptive choice?
A. Ortho Evra patches (EE & norelgestromin) apply for 3 weeks
then off 1 week
B. Depo Provera IM (medroxyprogesterone) 150 mg every 3
months
C. Extended cycle Seasonique (EE & levonorgestrel x 84 day)
D. Progestin only (Norethindrone 0.35 mg daily)
E. Lo/Ovral 28 (EE 30 mcg & norgestrel 0.3 mg)

Case #2b
Ms. Smith returns to the clinic after 3 months on the
medication. She is complaining of nausea, breast tenderness
and weight gain. What might be the reason for these
complaints? Has she been on it long enough? What options
below might be appropriate for Ms. Smith?
A. Ortho Cyclen 28 (EE 35 mcg & norgestimate 0.25 mg)
B. Ovcon 50 (EE 50 mcg & norethindrone 1 mg)
C. Jolivette (mini pill) (Norethindrone 0.35 mg)
D. LoSeasonique (extended cycle, EE 20 mcg & levonorgestrel
0.1 mg x 84 days)
E. Lessina (EE 20 mcg & levonorgestrel 0.1 mg)

Hormone
replacement

Oral

prescription

herbal supplements (soy, black cohosh)

Topical

patches and gels

Vaginal ring

Compounded bio-identical hormones

NOTE: importance of tapering when discontinuing

Other therapeutic
uses

Osteoporosis

Endometriosis

Androgen dependent prostate cancer in men

Hypersexuality (medroxyprogesterone)

Clinical Pearls

Breast cancer

Blood clots

Smoking

Cost

Administration

Adherence

Peanut allergy with Prometrium

Questions?

Resources

Wince L. Pharmacology of estrogens and progestins ppt. 29 Jan 2013.

Steroidal estradiol image: Adapted from Katzungs Basic & Clinical
Pharmacology, McGraw-Hill, 9th edition (2004).
PL Detail-Document #290305. Chart: Comparison of Oral Contraceptives
and Non-Oral Alternatives. The Pharmacists Letter/Prescribers Letter.
Updated March 2013. [Accessed 2 Feb 2014]
PL Detail-document # 280506. Chart: Postmenopausal Hormone Therapy.
The Pharmacists Letter/Prescribers Letter. Updated May 2012. [Accessed
2 Feb 2014]
Shrader S, Diaz V. Contraception. Chapter 88. Pharmacotherapy: a
physiologic approach. 8th edition. Table 88-2 Adverse effects of combined
hormonal contraception and their management. [accessed 2 Feb 2014].
Available at:
http://accesspharmacy.mhmedical.com.proxy.lib.ohio-state.edu/content.a
spx?bookid=462&sectionid=41100865
Drug information: Alesse, estradiol, . Lexicomp Drug Information
Smartphone app. [Accessed 2 Feb 2014]
Nilson J, Deng J, Brinton R. Impact of Clinically Relevant Progestins on the
Neural Effects of Estradiol and the Signaling Pathways Involved. Drug