Estrogens and Progestins/Oral Contraceptives Flashcards
Where are normal/endogenous progestins produced?
ovaries
What is the endogenous form of estrogen?
estradiol
What is the endogenous form of progestin?
progesterone
When is the follicular phase and what happens?
first half; 1-14 days
Ovaries: Ovarian follicles ripen, one mature one ruptures causing ovulation. Estrogens are secreted by maturing ovarian follicles causing endometrium changes
Uterus: endometrium prepares for nidation (implantation) by increasing in thickness and vascularity
FSH acts on developing ovarian follicles and helps them mature to produce estrogen
When is the ovulation phase and what happens?
Mid cycle
LH levels rise causing dominant folic to swell, burst, and release ovum
When is the luteal phase and what happens?
Second half; 15-28ish days
Ovaries: ruptured follicle evolves into corpus luteum where estrogen and progesterone are produced
Uterus: after ovulation the uterus continues its preparation by increasing secretory activity
If fertilization/implantation does not occur, the corpus luteum atrophies and the thickened endometrium breaks down causing menstruation
Therapeutic use of exogenous estrogens for non-contraceptive use(5):
1) menopausal hormone therapy: most common. usually accompanied with use of progestin.
2) female hypoginadadism: d/t ovarian failure, hypopituitarism, bilateral oophorectomy, turner syndrome (to promote breast development, mature reproductive organs, develop pubic hair, estrogen secretion)
3) acne: oral contraceptives
4) cancer: management of advanced prostate and some metastatic breast cancers
5) gender affirmation therapy for transgender women
Adverse effects of exogenous estrogen therapy:
- potential for endometrial hyperplasia/cancer, breast cancer, blood clots
- gallbladder dz, jaundice, HA/migraine
- fluid retention
- cholasma (patchy brown facial discoloration)
contraindications of exogenous estrogen therapy:
- hx of DVT, PE, stroke, MI
- pregnant
- vaginal bleeding with unknown cause
- hx of liver dz, estrogen-dependent tumors, breast cancer, usually
interactions of exogenous estrogen therapy:
- CYP34A/CYP1A2 inducers can lower estrogen levels. Inhibitors raise levels.
- May decrease effectiveness of anti-diabetic drugs and thyroid preparations
- can interacts with coags
preparations for exogenous estrogen therapy:
esterified form: plant based
synthetic conjugated: urine of pregnant horses
route of administration for exogenous estrogen therapy:
oral: estradiol available alone or in combo
transdermal: emulsions, spray, gels, patches
intravaginal: inserts, creams, vaginal rings
parenteral: IV/IM. IV rarely used, mostly for emergency control of heavy uterine bleeding
advantages of transdermal compared to oral for exogenous estrogen therapy:
transdermal total dose is greatly reduced because liver is bypassed, less N/V, blood levels of estrogen fluctuate less, lower risk for DVT, PE, CVA
patient education for for exogenous estrogen therapy:
transdermal patch: apply to C/D/I skin by pressing in place for 10sec. If it falls off, put it back on or replace. Remove old and replace with new 1-2x/week according to directions. Rotate site so not used more than 1x/week
transdermal emulsion: apply each morning to indicated location
transdermal gel: apply after showering to location indicated
transdermal spray: 1,2,or 3 sprays daily. Let dry for 2mins b4 dressing/30mins b4 washing
intravaginal cream: apply high in vagina at bedtime using applicator
intravaginal ring: insert as deeply as possible, leave in place for 3 most, remove and replace
intravaginal insert: 1 daily for 2 weeks, following by 1 2x/week after. Place as deeply as possible with applicator
prescribing considerations for for exogenous estrogen therapy:
- baseline data (HR, BP, weight, pregnancy test, TSH, lipid panel, screen for breast cancer and CVD)
- monitor BP and weight, triglycerides, TSH if patient on thyroid replacement as well. routine breast/pelvic exams. -endometrial biopsy for bleeding that continues for 6 mos
- high risk patients= do not prescribe: abnormal vaginal bleeding, estrogen-dependint cancer, hx of DVT/PE/CVA/MI, abnormal LFTs, pregnancy
SERMs purpose
created to receive benefits of estrogen while avoiding drawbacks
Tamoxifen purpose:
can inhibit cell growth in the breast, used to prevent and treat breast cancer
also protects against osteoporosis and favorable effect on lipids
Tamoxifen SE:
produces hot flashes, increases risk for endometrial cancer and blood clots
Raloxifene differences from Tamoxifen:
does not activate ERs in endometrium so no increased risk for uterine cancer
approved only for prevention and treatment of osteoporosis and prevent of breast cancer in high-risk women
Duavee purpose:
reduces risk for excessive growth of uterine lining
prevents vasomotor symptoms and osteoporosis in postmenopausal women WITH a uterus
contraindications are same as exogenous estrogen
Progestin MOA:
- receptors are found in cell nucleus
- must diffuse across the cell membrane, migrate to the nucleus and bind with a progesterone receptor (PR)
- PR complex binds with a progesterone regulatory element on a target gene
- PR-A: inhibitory actions
- PR-B: stimulatory actions
Therapeutic uses for progestin:
- menopausal HT (or hormone replacement therapy)
- dysfunctional uterine bleeding
- amenorrhea
- endometrial hyperplasia and carcinoma: can suppress hyperplasia, preventing cancer
- supporting early pregnancy and preterm birth
Adverse effects of progestin:
- 20% of patients experience breast tenderness, HA, and discomfort, arthralgia, depression
- when used for BC: spotting, breakthrough bleeding, irregular menses
- in combo with estrogen: increased risk for breast cancer in postmenopausal women
Routes of administration of progestin:
- oral
- IM
- SQ
- Vaginal insert
- Transdermal
Prescribing considerations of progestin:
same for estrogen
Menopausal hormone therapy, drugs used:
Estrogen alone (ET) or estrogen plus progestin (EPT)
- progestin present to combat negative effects of estrogen
- do not use progestin in women with hysterectomy
3 primary medical benefits for Menopausal hormone therapy:
1) suppression of vasomotor symptoms
2) prevention of urogenital atrophy
3) prevention of osteoporosis/fracture
Pregnant women considerations for estrogen and progestin:
estrogens contraindicated during pregnancy
high dose therapy of progestins during first 4 months of pregnancy assoc. with increased incidence of birth defects
Breast-feeding considerations for estrogen and progestin:
estrogens can affect infant development and may decrease quality of milk produced
progestins contribute to neonatal jaundice
Flibanserin- indications and adverse effects
- for women with low libido not assoc. with medical/mental health problem, relationship issues, med side effects
- d/c if no improvement within 8 weeks
- serious risks: CNS depression, hypotension w/ or w/out syncope
- only available through REMS
Bremelanotide- indications and adverse effects
-activates melanocortin receptors; MOA for improving sexual desire is unknown
-SubQ injection 45 mins b4 sexual activity. One dose in 24hrs max, no more than 8/month.
SE: N/V, HA, transient rise in BP 12hrs after taking, uncommonly has caused darkening of gums and portions of skin
Most effective vs least effective forms of BC:
most effective: nexplanon, IUD, sterlization
least effective: barriers, periodic abstinence, spermicides withdrawal
combination BC MOA:
estrogen inhibits follicular maturation while progestin acts in hypothalamus and pituitary to suppress LH surge which would normally cause ovulation. Also thickens cervical mucus to create a barrier to the penetration of sperm and alteration of endometrium making it less hospitable
Women of higher weight have less effectiveness with combination oral BC- true or false
True
Absolute contraindications vs relative contraindications of combination oral BC:
ABSOLUTE: -blood clots -CVA -coronary occlusion -abnormal liver fxn -breast cancer -undiagnosed bleeding -suspected/known pregnancy -smokers older than 35 RELATIVE: -HTN -DM -cholestatic jaundice of pregnancy -gallbladder dz -uterine leiomyoma -epilepsy -migraines
For women that experience acne and hirtuism switch to:
drospirenone or dienogest
For women that have DM switch to:
desogestrel or norgestimate
Drugs whose effects can be reduced by OC:
decrease benefits of warfarin and hypoglycemic agents, increases levels of clotting factors and increases BG `
Drugs whose effects are increased by OC:
theophylline, tricyclic anti-depressants, diazepam, chlordiazepoxide and can lead to toxic levels of these in the system
What do you do if one or more pills are missed in the first week of OC?
take pill ASAP and continue with pack, use another form BC for 7 days
What do you do if one of pills missed in 2-3week of OC:
take one pill ASAP and continue with active pills, skip placebo pills and go straight to new pack
What do you do if three of pills missed in 2-3week of OC:
follow instructions for 1 pill missed and used another form of contraceptive for 7 days
Dienogest and drospirenone:
greater risk for thrombosis. low risk for acne and hirtuism. risk for hyperkalemia
Progestin only OC:
- know as “mini pills” and do not cause thromboembolic events
- less effective and need to be taken at the same time every day
- use backup contractive if not taken same time every day and 7 days after starting
Interactions with nexplanon:
Barbiturates, phenytoin, rifampin, carbamazepine, topiratame, HIV protease inhibitors, St. John’s wart- all reduce efficacy
Considered good option for breastfeeding:
nexplanon after 21 days postpartum
Contraindications of mifepristone with misoprostol:
ectopic pregnancy, hemorrhagic disorders, use of anticoagulants, adrenal insufficiency, long-term glucocorticoid therapy
