female endocrine disorders - progesterone

progesterone

-secreted by ovary during second half of menstrual cycle (via LH)

-protects gestation

-suppresses menstruation and uterine contractility (prevents abortion)

progesterone moa

-binds to nuclear receptors

-complex dimerizes and translocates to nucleus

-binds to progesterone response elements (PRE)

-alters gene transcription

-cell response

progesterone pharmaco(physio)logical effects

-endometrial

-dyslipidemic

-mild diuretic

-insulin resistance

-hyperthermia

-suppressed menstruation and uterine contractility

-proliferation of acini in mammary gland

progesterone endometrium effects

-increased vascularization and maintenance

-reduces proliferation (thinning of endometrial lining)

progesterone dyslipidemic effect

-decreases HDL and increases LDL

progesterone: structural similarity to corticosteroids

-structurally similar to cortisol and aldosterone

-binds to MRs and GRs

progesterone mild diuretic effect

-anti mineralcorticoid activity

-Na and water loss

-counteracts estrogen-induced fluid retention, edema and elevated BP

progesterone insulin resistance effects

-inhibits glucose uptake = hyperglycemia

-cause of gestational diabetes

progesterone hyperthermia effects

-increases core body temp

-during late menstrual cycle and in pregnancy

progesterone suppresses menstruation and decreases uterine contractility effects

-prevents abortion

-protects gestation/pregnancy

progesterone proliferation of acini in mammary gland effects

-prepares breast for milk production after delivery

synthetic progesterones aka

-progestins

progestins

-long acting synthetic derivative

-vary in progestational activity and estrogenic and androgenic effects

-lacks anti-mineralcorticoid activity (except 4th gen)

first gen progestin examples

-norethindrone

-medroxyprogesterone acetate (MPA)

first gen progestins hormonal effects include

-high estrogenic and androgenic activity

second gen progestins examples

-levonorgestrel (LNG)

second gen progestins hormonal effects include

-no estrogenic activity

-very high androgenic activity

third gen progestins examples

-norgestimate

-desogestrel

third gen progestins hormonal effects include

-less androgenic activity

fourth gen progestins examples

-drospirenone

fourth gen progestins hormonal effects include

-anti androgenic activity

-anti mineralcorticoid activity

synthetic progestins clinical uses

-MHT in combination with estrogen

-contraception (alone or with estrogen)

types of hormonal contraceptives

-combined hormonal contraceptives (CHCs)

-progestin only contraceptives (POCs)

types of combined hormonal contraceptives

-oral (OCs)

-transdermal contraceptive

-vaginal ring contraceptive

types of progestin only contraceptives

-oral progestin only pills (POPs)

-long acting injectable

-long acting implantable

-long acting intra-uterine device (IUDs)

estrogens hormonal contraceptives moa

-suppress FSH release to prevent development of dominant follicle that surges LH and ovulation

-stabilizes endometrial lining and provide cycle control

progestins hormonal contraceptives moa

-GnRH inhibition > block LH surge > inhibit ovulation

-thickening cervical mucus prevent sperm penetration

-slowing tubal motility/peristalsis delaying sperm transport

-induce endometrial atrophy

combined oral contraceptives (COCs)

-significantly high estrogen and progestin

-3 types of COCs

3 types of COCs

-monophasic

-biphasic

-triphasic

monophasic OCs

-same amounts of estrogen and progestin for 21 days

-followed by 7 day placebo phase

biphasic OCs

-two varying amounts of estrogen and progestin for 21 days

-followed by 7 days placebo phase

triphasic OCs

-three varying amounts of estrogen and progestin for 21 days

-followed by 7 day placebo phase

COCs ADEs

-breakthrough bleeding

estrogen specific

-nausea

-vomiting

-headache

-breast tenderness

-edema, HTN

-gall bladder disease

progestin specific

-incr appetite

-weight gain

-acne

-hirsutism

COCs drug interactions

-CYP inducers

-antibiotics

antibiotic drug interactions with COCs

-abx limit bacterial flora and reduce estrogen reabsorption

-reduce contraceptive efficiency

COCs estrogen contraindications

-history of DVT, uncontrolled HTN, CVD/stroke

-migraine

-older than 35 y/o and smoking 15 cigs per day

-liver disease

-breast cancer

-pregnancy, lactation or less than 6 week postpartum

transdermal contraceptives (TC) examples

-Ortho Evra

Ortho Evra

-contains EE and norelgestromin

-once a week administration

Ortho Evra limitations

-effective only in pts weighing less than 90kg

Ortho Evra ADEs

-like COCs

-application site reactions

Ortho Evra warnings

-increased risk of VTE, heart attack, and strok

vaginal contraceptive ring examples

-NuvaRing

NuvaRing

-containing EE and etonogestrel

-3 weeks of use and 1 week without

NuvaRing advantages over COCs

-less breakthrough bleeding and spotting

-better menstrual cycle control

NuvaRing ADEs

-like COCs

device related issues such as

-foreign body sensation

-device expulsion and vaginal symptoms

progestin only pills (POPs/mini pills) moa

-works all 4 mechanisms but doesn’t always block ovulation

POPs advantages

-can be used in women who cannot take estrogen

POPs disadvantages

-less effective than COCs

-must be taken every day consistently

-high risk of ectopic pregnancy

-more breakthrough bleeding

long acting injectable contraceptive example

-Depo-Provera

Depo-Provera

-contains medroxyprogesterone acetate (MPA)

-IM or SC every 3 months

Depo-Provera moa

-sustained progestin blocks LH surge inhibiting ovulation

Depo-Provera limitations

-not desireable in women planning pregnancy soon after cessation of therapy

-ovulation suppression can persist up to 18 months after last injection

Depo-Provera ADEs

-breakthrough bleeding

-amenorrhea

-weight gain

-short term bone loss

-should not be used for more than 2 years

long acting implantable contraceptive examples

-Nexplanon

Nexplanon

-SC progestin implant containing etonogestrel

-same MOA as Depo-MPA

Nexplanon advantages over POPs and Depo-MPA

-extremely effective (lasts up to 3 years)

-fertility returns relatively short after cessation of therapy

Nexplanon ADEs

-breakthrough bleeding

-fibrosis around device

-difficulty removing

-pain at site

-other side effects associated with progestins

IUD examples

-Mirena

-Skyla

-Liletta

-Kyleena

-all contain levonorgestrel

IUD moa

-localized action

-blocks implantation and thins out uterus endometrial lining

IUD advantages

-quick onset and offset

-long duration of action (up to 5 years)

-reduction in menstrual blood loss

-very low systemic absorption

IUD ADEs

-breakthrough bleeding

emergency contraceptives (ECs)

-morning after pills

ECs moa

-inhibiting or delaying ovulation

-increasing cervical mucus

-preventing implantation

3 types of ECs

-high dose progestin only

-ulipristal

-copper IUD

high dose progestin only ECs examples

-PlanB

-Next Choice

-LNG Tablets

-1 or 2 divided doses of LNG

high dose progestin only ECs directions

-should be taken within 72 hrs

-2nd dose must be taken 12 hrs later

high dose progestin only ECs ADEs

-nausea

-headache

-abdominal pain

-breast pain

-irregular bleeding

Ulipristal EC

-Ella

-selective progesterone receptor modulator (SPRM)

Ulipristal advantage

-effective if taken within 120 hrs

Ulipristal ADEs

-headache and abdominal pain

copper IUD EC

-Paragard

-non hormonal EC

copper IUD moa

-copper affects sperm motility

-prevents fertilization and implantation

copper IUD advantages

-most effective option of EC

-contraception lasts for 10 yrs

copper IUD ADEs

-excessive vaginal bleeding

abortifacents for pregnancy termination

-mifepristone

mifepristone moa

-progesterone receptor blocker

-degrades uterine lining and contraction

-used in combination with misoprostol

mifepristone ADEs

-excessive vaginal bleeding