RH Exam 1.docx

Female menstrual cycle: Physiology and pharmacology Anatomy review: (Define the following) Uterus is where the sperm and egg meet includes the: Cervix: thins & dilates during childbirth Endometrium: dynamic during the cycle; site of implantation Myometrium: muscular wall of uterus Uterine...

Female menstrual cycle: Physiology and pharmacology Anatomy review: (Define the following) Uterus is where the sperm and egg meet includes the: Cervix: thins & dilates during childbirth Endometrium: dynamic during the cycle; site of implantation Myometrium: muscular wall of uterus Uterine tubes (also known as ovaducts, fallopian tubes) transport oocytes (egg cells) released from ovaries to the uterus. This is facilitated by beating action of cilia (lining uterine tubes) so create a current to help move egg cells along. There is no direct connection b/w opening of uterine tubes and ovary. Oocyte is released into open space and drawn into tube by beating cilia. Ovaries release egg cells. This is the site of follicle development Vagina Oogenesis (development of female gametes) occurs within structures called follicles. During prenatal development, millions of primordial follicles are formed. These consist of single, large cell called an oocyte, which is surrounded by layer of follicular cells. No new primordial follicles appear- degenerate as female ages- only 400-500 oocytes usually released from ovary Follicular development Primordial follicle – one layer of squamous-like follicle cells surrounds the oocyte Primary follicle – one or more layers of cuboidal granulosa cells enclose the oocyte Granulosa cells produce the zona pellucida, provide nutrients, and “protect” the germ cell Graffian follicle (mature follicle) – fluid filled antrum ovulation: ruptures to release oocyte Corpus Luteum – ruptured follicle after ovulation; very large! Each month, 3-30 follicles will begin maturation within the ovary. Around day 7 on the cycle, 1 follicle becomes dominant, and the others die through a process called atresia. This is because the dominant follicle produces estrogen, which provides negative feedback to the pituitary, inhibiting FSH release. Increased estrogen production until day 12-14 (150 picograms/mL for 36 hrs or more; high estrogen level) Menstrual cycle: Day 1: Bleeding starts; follicular phase Defined as first day of menstrual bleeding – lower levels of estrogen and progesterone. GnRH secretion from hypothalamus results in release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary FSH stimulates the development of 3-30 follicles within the ovary. Larger follicles will begin to excrete estrogen This is the follicular phase of the ovary. Day 7: One follicle becomes dominant, as under the direction of FSH, this follicle produces estrogen, which provides negative feedback to the pituitary, inhibiting FSH release. Thus, other follicles lose hormonal support and die through atresia. Day 7-12: Dominant follicle grows and matures- becomes mature follicle. It produces more and more estrogens, which initially provide negative feedback to gonadotropin release. Estrogen also causes the endometrium to become thicker. ~Day 13: High levels of estrogen (150-200 pg/mL for 36+ hrs) secreted by mature follicle cause positive feedback to gonadotropin release (FSH/LH release). Day 14: The mid-cycle LH/FSH surge causes the follicle to rupture, inducing ovulation. Ovulation is the release of the oocyte from the ovary. An LH Surge indicates ovulation. Luteinizing Hormone causes the ruptured follicle to become a corpus luteum, thus entering the luteal phase of the ovary. Day 15-25: Luteal phase The corpus luteum secretes estrogen, progesterone, and inhibin. These hormones provide negative feedback to gonadotropin release (so don’t develop new follicles). Estrogen and progesterone support the endometrium; estrogen causes endometrium to be proliferative (thicker, cells divide, grow endometrium), progesterone causes the endometrium to become secretory (nutritional environment = uterine milk). Also inhibin Day 25-28: Unless the hormone human chorionic gonadotropin (hCG) signals pregnancy, the corpus luteum begins to degenerate. As a result, estrogen and progesterone levels start to fall, shed endometrium Day 1: Corpus luteum degenerated Low levels of estrogen, progesterone, and inhibin Allow for cycle to restart (lose negative feedback to gonadotropins) Lose hormonal support for endometrium = bleeding occurs In the ovary: developing follicles which are releasing estrogen (tells endometrium to proliferate/thicken) Estrogen – endometrium proliferative (divide, increase thickness) Progesterone – transforms endometrium into secretory endometrium (nutritional); uterine milk Menstrual cycle – ovarian phases Luteal Phase The corpus luteum secretes progesterone and estrogen Inhibits gonadotropins and maintains endometrium Fertilization? No Estrogen and progesterone levels fall Endometrial shedding (menstruation) and begin cycle (GnRH- FSH/LH secretion due to loss of negative feedback) o Yes hCG prevents regression of corpus luteum (continued estrogen and progesterone) until placenta takes over that role hCG binds to LH receptors, prompts corpus luteum to stay around and continue secretion Highest level of estrogen right before mid-cycle, prompting positive feedback of LH/FSH Continue to secrete estrogen by the corpus luteum LH prompts ovulation Don’t see progesterone until luteal phase (transform uterus into more secretory/nutritious) Oocyte viable 12-24 hours Slight increase in basal body temp after ovulation Sperm can survive for 72 hours So 3-4 day window around ovulation when pregnancy can occur Female hormones and therapies: Physiology and Pharmacology of Estrogen & Progesterone Natural/Endogenous Estrogens Estrogen (18-Carbon, 17-beta-hydroxyl, aromatic A-ring) estradiol (E2) Most potent for both estrogen receptor and estrogen receptor mediated actions estrone (E1) Second most potent Ketone at C-17 allows for estrogen receptor binding estriol (E3)* Weak estrogen and minor female sex hormone estetrol(E4)* Estradiol is the major secretory product of ovary The pathway to estrogen production varies from follicular to luteal phase. (during follicular phase, developing 3-30 follicles which start to secrete estrogen; during luteal phase, corpus luteum is secreting estrogen, progesterone, inhibin) What hormone is a precursor for estrogens in the luteal phase? Progesterone Available estrogens synthetic alterations increase oral bioavailability Ethinyl estradiol (EE): steroidal, synthetic Primary estrogen used in oral contraceptives Ethinyl (triple bond) substitutions at C17 increases oral potency (inhibits first-pass hpatic metabolism) Mestranol: steroidal, synthetic Inactive, must be converted to EE in the liver 50% less potent that EE Estetrol: steroidal, natural, can also be synthesized Long-half life (24-28 hrs) Minimally metabolized, if at all- not reconverted to estradiol Other therapeutic Estrogens Esters of Estradiol: increases duration, so usually delivered intramuscularly (prolonged doses for menopause or hormone therapy in trans patients). Esters helps ensure long half life Conjugated Estrogens: mixture of sodium salts and sulfate esters of estradiol SAR of Estrogens Aromatic ring A, C-3 hydroxyl, and C-17 hydroxyl (or ketone) are essential for estrogenic activity. Substitution of steroid nucleus usually reduces activity C-11 ethyl or C-11 methoxy increases estrogen receptor affinity Modification at C-17 and C-16 are tolerated to reduce first pass metabolism Unsaturation (double bonds) in Ring B DECREASES estrogenic potency What are non-steroidal compounds with estrogenic activity? Bisphenol A and Genestein Bisphenol A has 2 unsaturated rings with hydroxyl groups Genestin is a 3 membered ring with 2 unsaturated rings and hydroxyl groups on Ring 1 and 3 Kinetics – highly protein bound (steroids won’t be happy in plasma) Bind to sex hormone-binding globulin (SHBG) Estradiol is converted in liver to estrone and estriol (low affinity for ER). estrone, estriol, their derivatives, and their conjugated metabolites are excreted in bile Conjugated metabolites may be hydrolyzed in intestine to active, re-absorbable compounds – can circulate within the entero-hepatic circulation. Hepatic effects are significant: increased synthesis of clotting factors and angiotensinogen – increased BP and risk for clots (this can be minimized by routes that avoid first pass, so not an oral product) Estrogen pharmacology (timeline for response from binding to response: 8-12 hours, but can have immediate effect on cells estrogen receptors on plasma membranes) Estrogen Response Elements (ERE) – in promotor region of genes that are regulated by estrogen Binds to receptors ER-alpha (major) and ER-beta To be activated the receptors must form complex of proteins. These bind to DNA in promoter sequences that have estrogen homodimer in them. However, the receptors may regulate other genes via interactions with transcription factors. There are also plasma membrane estrogen receptors These may activate other transcription factors and/or have effects on second messenger systems inside the cell Estetrol has differential effects on plasma membrane Estrogen effects Female maturation at puberty Development of vagina, uterus, uterine tubes Secondary sex characteristics: Development and growth of breast Accelerated growth phase (puberty), followed by early closing of epiphyses of long bones Contribute to growth of axillary and pubic hair Alter distribution of body fat Hyperpigmentation of skin (particularly areolae and genital region) Uterine effects hyperplasia of endometrium (estrogen is proliferative, so can cause hyperplasia if unchecked – use progesterone, can promote risk for cancer); ONLY use estrogen alone in women with hysterectomy. watery cervical mucus (high estrogen = very watery and easier to be penetrated by sperm right before ovulation) Skeleton effects Required in females AND males for normal skeletal development Antiresorptive (inhibits osteoclasts which break down bone) – this is why women going through menopause (large drop in estrogen) are at risk for bone loss Cardiovascular system effects maintenance of normal structure and function of blood vessels regulate triglycerides and lipoproteins: generally elevates triglycerides, lowers LDL, elevates HDL, and decreases cholesterol Liver effects Alter production of proteins, increase CBG, TBG, SHBG, increase clotting factors, angiotensinogen Blood coagulation Enhance coagulability of blood CNS Cognition and memory Mood: large drops in estrogen associated with depression Other clinically important targets: colon, urogenital tract, eyes Clinical Uses of Estrogens Deficiency after ovarian failure or after natural or surgical menopause Infertility/IVF: maintain thick endometrium Contraception: if breastfeeding, progesterone only Suppression of postpartum lactation (inhibits PRL) Carcinoma of the prostate: estrogen opposes actions of androgen Reduce hirsutism due to androgen production in females Reduce Acne: oppose actions of androgen Adverse effects Uterine bleeding (hyperplasia) Cancer Progesterone can protect against endometrial risk, but not breast cancer risk Other effects Nausea Breast tenderness Hyperpigmentation or melasma (pregnancy mask and linea nigra) Migraine headaches – continuous low level of estrogen can be used to treat Hypertension (increased angiotensinogen) Blood clots (increased clotting factors) What are some nuclear ER effects? Prevents plaque formation (vascular system) Impacts liver lipid metabolism Maintains bone mineral density Supports tissue maintenance in uterus and vagina What are some membrane ER effects? Stimulates breast growth, reduces risk of breast cancer Impacts liver lipid metabolism Maintains bone mineral density Regulates vascular tone, repairs and maintains tissue Nuclear dependent receptors and membrane dependent receptors have different effects on the vascular system. Nuclear dependent ER prevents plaque formation whereas membrane dependent ER regulates vascular tone and repairs and maintains bone mineral density. Other nuclear dependent effects occur in the uterus and vagina, here estrogen supports tissue maintenance in both. Membrane dependent receptors uniquely stimulates growth in the breast. Native Estrogen with Selective actions in Tissues (NEST): agonist ERalpha is selective and acts as a nuclear receptor agonist and membrane receptor antagonist. This brings about selective effects depending on tissue type! NEST drugs will promote Nucelear-dependent effects and prevent membrane-dependent effects. This means: Breast growth will NOT be stimulated (membrane-dependent is antagonized) Nuclear effects will be promoted such as: preventing plaque formation in the vascular system, and tissue maintenance in the uterus and vagina Estetrol will select for the nuclear ER effects. The SERMs = Selective Estrogen Receptor Modulators (agonist (increase activity) in certain tissues and antagonist (inhibit) in others) Inhibit ER activity in some tissues/increase it in others Tamoxifen (Soltamox): first SERM ANTAGONIST in the breast (used in breast cancer) – you don’t want to stimulate growth AGONIST in uterus and bone (antiresorptive, prevents break down of bone) Reduced risk of atherosclerosis Adverse effects: hot flashes, irregular periods, BBW: uterine malignancies and clot risk Raloxifene (Evista) Similar effects as estradiol on lipids and bone ANTAGONIST in breast – good for breast cancer risk Similar to tamoxifen, but no agonist activity in uterus (decreases uterine malignancy risk) Used for postmenopausal osteoporosis (agonist in antiresorption in bone) Breast cancer prophylaxis High 1st pass effect, long half-life (>24 hrs) Adverse effects: hot flashes, clot risk Clomiphene Partial agonist in hypothalamus/pituitary; used in infertility Long-term binding of ER (weeks) results in downregulation in ERs Lose negative feedback (estrogen receptors are what drives negative feedback) Stimulates GnRH, FSH/LH release Adverse effects: hot flashes, stimulation of ovaries (ovarian enlargement), nausea and vomiting, multiple pregnancies (10%) Progestins (compounds with biological activities that are similar to those of progesterone) Natural: Progesterone (double bond at C4 in the A-ring) Precursor to estrogens, androgens, and adrenocortical steroids Precursor to estradiol during the Luteal phase Synthesized in ovary (corpus luteum), testis, adrenal gland, placenta Effects of Progesterone Development of secretory apparatus in the breast – prompts breast to produce milk Secretory endometrium Opposes proliferative action of estrogen in uterus (anti-estrogenic) – less ability for sperm to penetrate Increases viscosity of cervical mucus, decreases motility within uterine tubes Favors fat deposition Increases basal insulin and insulin response to glucose Increases body temperature Hypnotic effects in brain (estrogen does the opposite) Kinetics of Progesterone Rapidly absorbed Half life ~ 5 min Almost completely metabolized after first pass Many synthetic progestins have increased bioavailability Synthetic Progestins Highly dependent on: C17 substituent, C19 methyl group, C13 ethyl Three structural classes of progestins include: Pregnanes – agents similar to Progesterone Medroxyprogesterone Acetate (Depo-Provera) - a long acting contraceptive) C6 increases lipophilicity (increases half-life) Estranes – agents similar to 19-Nortestosterone Norethindrone (1st generation OC) Gonanes – agents similar to 19-Norgestrel; (this is most commonly found in OC) Norgestimate Desogestrel – a gonane missing a keto group which negatively impacts progestin activity but lowers androgenic side effects Which have some androgenic activity? Medroxyprogesterone acetate Norethindrone Levonorgestrel What effects would you expect due to this? Increased sex drive, hirsutism, sebum/acne Mechanism of Progestins Enter cell and bind to progesterone receptors (cytoplasm and nucleus) Progesterone receptors = PRalpha and PRbeta Dimerize and bind to PREs to activate gene transcription SAR of Progestins Double bonds in rings B & C INCREASE activity at the progesterone receptor Halogen at C6 or C7 INCREASE activity at the progesterone receptor Adding C11 methyl INCREASES activity at the progesterone receptor Removing C19 methyl INCREASES activity at the progesterone receptor Removing 3-keto DECREASES activity at the progesterone receptor Modifications at C17: Alkyl groups enhance bioavailability Acetyl groups increase duration Progestins: Clinical uses HRT - hormone replacement therapy Hormonal contraception Long-term ovarian suppression Levonorgestrel IUD (Mirena IUD) Plan B MOA is to prevent fertilization by altering tubal transport of sperm and/or ova Medroxyprogesterone acetate (Depo-Provera): q3months etonogestrel/ethinyl estradiol (NuvaRing) Fertility For optimum secretory transformation of the primed endometrium Delay of premature labor Levonorgestrel and norgestrel are safest but may have more androgen related ADEs Drospirenone and dienogest are structurally similar to spironolactone Clot risk is greater with newer than older So…how would progestins be given to stimulate or maintain pregnancy? Give progestins during the Luteal Phase to transform a proliferative uterine endometrium into a more differentiated, secretory one. During pregnancy, maintain secretory uterus to help with pregnancy. How would progestins be given to prevent pregnancy? During follicular phase or continuously to prevent ovulation, increase viscosity of cervical mucus, decrease motility within uterine tubes, and create atrophic endometrium Progestins: Effects Risks: Break-through bleeding May increase blood pressure (aldosterone effect?) Weight gain, edema Some synthetic progestins have weak androgenic activity, which may increase sebum/acne Benefits: decreased incidence of endometrial and ovarian cancer Progesterone Antagonists Mifeprestone (RU-486): progesterone antagonist, but more active as glucocorticoid antagonist Can terminate pregnancies in first 7 weeks in 95% of women (with prostaglandins) Adverse effects: delayed ovulation in following cycle, prolonged bleeding, vomiting, diarrhea, abdominal pain Hormonal Contraception Oral contraception: prevent ovulation, prevent endometrium from being proliferative, thick cervical mucous combination pills contain estrogens and progestins Monophasic includes: 21/7: Aviane, Yasmin, Safyral, Levora, Low-Ogestrel, Alyacen, Ortho-Cyclen or Sprintec Extended cycle 24/4 (shorter periods): Junel Fe, Yaz, Beyaz, Layolis FE (chewable), Nextstellis (NEST) Extended cycle (fewer periods): Amethyst, Seasonale, Introvale Mutliphasic includes: Traditional: Ortho Tri-Cyclen, Tri-Sprintec, Tri-Cyclen Lo, Tri-Lo-Sprintec, Estrostep Extended cycle (shorter): Lo Loestrin FE, Natazia Extended cycle (fewer): Seasonique, LoSeasonique Progestin-only pill (POP)/Mini-pills: continuous progesterone alone (not as good as preventing ovulation) Camila, Errin, Heather, OrthoMicronor, Slynd OTC: Opill Patch (monophasic): Xulane, Twirla Vaginal Rings (monophasic): Nuvaring, Annovera IM injections: DMPA Implantable contraceptives: Nexplanon (etonogestrel) IUDs: Mirena, Liletta, Kyleena, Skyla (levonogestrel); ParaGard (non-hormonal copper) Gel (non-hormonal): Phexxi Mechanism of action Combination pills: Negative feedback to pituitary, resulting in inhibition of ovulation Changes in cervical mucus: Estrogen makes it watery, progestin makes it thick & sticky Uterine endometrium: not as thick Motility and secretion in uterine tubes? less Progestin alone Does not always inhibit ovulation Changes in cervical mucus: thick and sticky Uterine endometrium: not as thick Motility and secretion in uterine tubes: less Uses Contraception Failure rates low Exceptions: phenytoin and antibiotics– enhance metabolism Endometriosis – stop growth w/ progestin Acne: androgenic activity Effects Chronic use of combination agents depresses ovarian function 2% may remain amenorrheic for periods up to several years! Some breast enlargement with estrogen-containing agents Estrogens may suppress lactation (decreased PRL) CNS: estrogens tend to increase excitability, progestins depress it Endocrine: inhibition of LH, FSH; increase renin and aldosterone secretion Blood: increase in clotting factors Liver: Effects on serum proteins, alterations in hepatic drug excretion and metabolism Lipids: progestins tend to antagonize effects of estrogen Carbohydrates: progestins increase insulin release Skin: hyperpigmentation – estrogen; some androgen-like progestins increase sebum, acne; estrogen- suppresses androgens, decreases sebum and acne Mild adverse effects Nausea, breast pain, breakthrough bleeding, edema (estrogen) Changes in serum proteins or endocrine changes Headache – occasionally migraines are exacerbated Moderate adverse effects: For effect, note if effect is due to progesterone or estrogen in blanks Breakthrough bleeding with progestin agents or with low dose combo pills Weight gain: combination agents containing progestins or progestin alone Increased skin pigmentation (estrogen) Acne (androgen-like progestins) Urethral dilation (estrogen), increased risk of UTI Vaginal infections Amenorrhea (following discontinued use) Severe adverse effects: For effect, note if effect is due to progesterone or estrogen in blanks Thromboembolism – 3x risk (estrogen) Not related to age, mild obesity, or smoking! MI – risk higher with obesity, hypertension, hyperlipoproteinemia, or diabetes Much higher risk in smokers! Acceleration of atherogenesis due to decreased glucose tolerance, decreased HDL, increased LDL, platelet aggregation (progestin) Cerebrovascular disease: Stroke (estrogen) Risk in women over 35, increased in smokers Cholestatic jaundice progestin Depression (~6% of patients) Cancer Reduce endometrial and ovarian cancer risk, increase breast in younger women (estrogen) PhexxiTM Contraceptive vaginal gel Lactic acid, citric acid, potassium bitartrate Vaginal pH 3.5-4.5: How does this prevent pregnancy? 86% efficacy with “typical use” and 93% when used as directed Adverse effects: vulvovaginal burning sensation, vulvovaginal pruritus, vulvovaginal mycotic infection, urinary tract infection, vulvovaginal discomfort, bacterial vaginosis, vaginal discharge, genital discomfort, dysuria, and vulvovaginal pain Dr. Flores Material Hormonal contraception risks Increased risk of STIs (due to decrease use of barrier method) Menstrual changes Hormonal adverse effects MI/CVA/VTE, HTN Gallbladder dx (estrogen) Hepatic tumors Cervical cancer Method-related Failure Reasons for stopping include: side effects, difficulty with use, safety concerns, and lack of access to health care Non-contraceptive benefits Reduced risk of endometrial or ovarian cancer CHC: Relief of benign breast disease, prevent ovarian cysts, improve acne control, improve menstruation regulation Decrease in endometriosis symptoms (extended cycle) Reduction in anemia risk (less/shorter menses, iron) Reduction in risk of fetal neural tube defects (folate, planning) Relief from PMDD symptoms (drospirenone) Dispense a package insert with every oral contraceptive Paragard and Phexxi are nonhormonal Estrogen-containing Advantages: shorter, lighter, more predictable periods Disadvantages: no STI protection, increased risk of CVA/MI/VTE, adverse events: spotting or breakthrough bleeding, nausea, bloating, breast tenderness, headache. Estrogen-containing contraceptives are a good choice if need high efficacy, reversibility, and safety Do NOT use for people 35 years or older who smoke greater than 15 cigarettes/day Major risk factors with <35 mcg EE are CV Monophasic oral (preferred regimen) Drospirenone has higher clot risk in some populations; also has anti-androgenic benefits Levomefolate: folic acid Nextstellis (estetrol/drospirenone) is monophasic Recall that estetrol is a synthetic analog of a natural estrogen synthesized by the fetal liver and present only during pregnancy. It is not metabolized to estradiol or estriol Estetrol is selective for nuclear estrogen receptors = NEST First Day Start or use back up for 7 days CI in renal and/or hepatic impairment WEIGHT RESTRICTION: BMI >30 Missed/late doses (COC) If 1 missed pill: take now and next pill at usual time (back-up not required); consider EC if multiple single misses in the same cycle If 2 or more missed pills: Early in pack: take most recent missed pill now and discard other missed pills and continue regimen; use back-up for 7 days Last week: skip placebo and start next pack. Use back-up for 7 days Transdermal patch (monophasic) – avoid in BMI >30 and patients who smoke Xulane Releases EE for 9 days Advantages: less DDI, good for patients with dysphagia WEIGHT RESTRICTION: less effective if >90kg (198 pounds); CI if BMI >30kg/m2 (VTE) Twirla Releases EE daily Lower dose, round DO NOT use if BMI >30 - reduced efficacy and higher VTE risk Counseling points: apply to abdomen, buttocks, upper torso or upper arm at the beginning of the menstrual cycle Apply 1 patch once weekly for 3 weeks then patch free on week 4 If you forget to change: <48 hrs Change NOW and consider EC >48 hrs Change NOW and use back up for 7 days If patch detaches for greater than 24 hours – restart the 4 week cycle and use back up for 7 days If delayed application in 3rd week: omit hormone free week and start NOW Estrogen can reduce the efficacy of lamotrigine Estrogen efficacy is impacted anti-epileptics and rifampin STOP OC and seek care asap if Severe abdominal pain, chest pain or cough/SOB, Headache Eye problems, speech problems Severe leg pain in calf or thigh Vaginal Ring (monophasic) Nuvaring Refrigerate prior to dispensing Insert and leave in place for 3 weeks then 1 week with no ring Annovera (re-use) Leave in place for 21 days, remove for 7, no refrigeration, good for up to 13 cycles DO NOT use if >35 and smoking CI: ombiasvir/paritaprevir/ritonavir Counseling Points: Insert on or before 5th day of menses If it falls out: <3 hours: wash and re-insert >3 hours: use back up for >7 days If forget to insert: Consider EC, insert new ring and use back up for 7 days Do not use diaphragm/female condom, caution with tampons Estrogen Considerations: Other hormone considerations Low Pregestational Activity for progestin sensitive women (fatigue, history of weight gain) Low Androgenic Activity for androgen sensitive women (oily skin, acne hirsutism). Low androgenic activity progestins include: norgestimate, desogestrel, drospirenone Consider extended cycle or progestin only for heavy menstrual bleeding, anemia, dysmenorrhea, endometriosis, migraines Consider drospirenone or extended cycle (Yaz, Beyaz, Introvale) for PMDD Consider Tri-Sprintec or Yaz for acne For estrogen ADE or sensitivity, consider progestin only Progestin only (POP, injectable, implant, IUD, EC) “mini-pill” POP include: Camila, Errin, Heather, Ortho Micronor Advantages: no estrogen risk, can be used postpartum, minimize menses (possible ammenorhea) Disadvantages: no STI protection, unpredictable bleeding, mood changes, weight gain, slightly less effective than CHC No pill free or hormone free period Must take at same time EVERYDAY If >3 delay in oral dose, take dose and use back up for 48 hrs and consider EC Opill is an over the counter POP Slynd is a POP with 4 inert pills and allows for 24 hours missed pill window Monitor potassium Consider IUDs and implants as first-line methods Injectable progestin: DMPA – Medroxyprogesterone acetate Not quickly reversible Benefit in sickle cell disease, seizure disorders, and endometriosis associated pain Disadvantages: Use for more than 2 years only if other methods are inappropriate; Supplement 1200-1500mg Calcium with 400 IU Vit D and weight bearing exercise Delayed return to fertility Levonorgestrel IUD Thickens cervical mucus, local effects suppress endometrium Insert at any time once confirmed non-pregnant Use back up for 7 days unless inserted within 7 days of menses start CI if distorted uterine cavity, cervical cancer, endometrial cancer, gestational disease, PID, unexplained vaginal bleeding Mirena and Liletta can be inserted up to 8 years Kyleena up to 5 years Skyla up to 3 years First line for adolescent and nulliparous ParaGard IUD can remain up to 10 years Copper ions induce an inflammatory reaction in the uterus to interfere with sperm’s ability to reach fallopian tube and decrease sperm’s ability to fertilize Phexxi is a nonhormonal contraceptive gel. Insert 1 applicatorful vaginally 0-60 mins prior to intercourse