Estrogen & Progesterone Contraceptives

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Estrogen and Progesterone Contraceptives Types: Oral combined pills (estrogen + progesterone) Transdermal patch (E+P) Vaginal rings (E+P) Mechanism of action & absolute contraindications are same. Oral Combined Pills (OCPs) Classification by Estrogen Component (Ethinyl Estradiol - EE) High dose pills: EE > $50 \mu g$ (not used now) Low dose pills: EE Very low dose pills: EE Minimum effective dose: $10 \mu g$, called Loestrin Classification by Progesterone Component (Generation) 1st Generation 2nd Generation 3rd Generation: Least androgenic effects. Examples: Gestodene, Norgestimate, Desogestrel (most common), Etonorgestrel. 4th Generation: Anti-androgenic properties. Examples: Drospirenone: Derivative of spironolactone. Aldosterone antagonist (antagonizes salt & water retention by estrogen). Anti-androgenic action by increasing sex hormone binding globulin $\rightarrow$ decreasing free testosterone. Used for patients with mild hypertension, salt and water retention. Dienogest Nomegestrol Mechanism of Action (OCPs) Estrogen + Progesterone Decreased Gonadotropin Releasing Hormone (GnRH) $\rightarrow$ Decreased LH & FSH (FSH > LH) $\rightarrow$ Anovulation (main mechanism) Thickens cervical mucosa Decreases tubal motility Decidualization of endometrium $\rightarrow$ Thinning of endometrium Endometrium becomes unsuitable for implantation Composition of Important Pills Pill Composition Comment Mala D $30 \mu g$ EE + $0.15 mg$ Levonorgestrel (LNG) Sold by Government of India at subsidized rates. Mala N $30 \mu g$ EE + $0.15 mg$ Levonorgestrel (LNG) Distributed free by Government of India. Yasmin $30 \mu g$ EE + $3 mg$ Drospirenone 4th generation OCP. Starting a Pill Start on day 1 of the cycle (no backup needed). Can be started from day 1-5 of cycle (no backup needed). If started post day 5, additional contraception for 1 week. Take daily at same time. After 21 days, stopping pill causes menstruation (3-4 days). Bleeding starts again on day 1 of next cycle. Breakthrough bleeding: Most common side effect. Due to missed doses. 24-pill packs used to avoid it. Non-Contraceptive Uses of OCPs Regularize cycles in irregular menstruation / PCOS. Prevent excessive bleeding / reduce blood loss in hyperestrogenic conditions (fibroids, endometriosis). Manage abnormal uterine bleeding (AUB) - as estrogen increases progesterone receptors, and progesterone binds to endometrium, stopping bleeding. Make cycles anovulatory to reduce pain in primary dysmenorrhea / endometriosis. Manage functional ovarian cyst, menstrual migraine, mittelschmerz syndrome. Manage premenstrual syndrome (PMS) - Fluoxetine (SSRI) is drug of choice. Estrogen component used as hormonal replacement therapy (HRT) and management of Turner syndrome. Progesterone component makes cervical mucosa thick $\rightarrow$ decreases chances of PID, STD, ectopic pregnancy. MC PID with OCP use $\rightarrow$ Chlamydia. MC vaginitis with OCP use $\rightarrow$ Candidiasis. Manage hirsutism (DOC), acne, hyperandrogenism (decreases GnRH, LH, androgens). OCP Effect on Cancers Increases Relieves/Decreases No effect Hepatic adenomas Endometrial cancer Liver cancer Breast cancer in premenopausal females Ovarian cancer Cancer cervix (reversible; risk reduces after stopping) Ovarian cysts Benign breast diseases Colorectal cancer Absolute Contraindications of OCPs (WHO Category 4) Mnemonic: BANKS Have Various Schemes To Provide Home Loans During May B anks: Known/suspected breast cancer. H ave: Uncontrolled hypertension ($>160/110$ mmHg). Medically controlled hypertension in non-smoking females of any age is NOT a contraindication. V arious: Undiagnosed vaginal bleeding. S chemes: Smoker > 35 years of age. T o: Known/suspected case of thromboembolism or family history of idiopathic thromboembolism (parent/sibling) or h/o CVA/MI, or conditions predisposing to it (e.g., malignancy, lupus anticoagulant, prolonged immobility). P rovide: Pregnancy or h/o peripartum cardiomyopathy. H ome: Severe hypercholesteremia, hypertriglyceridemia ($>750$ mg/dL). L oans: Presently impaired liver function / liver cancer / acute or chronic cholestatic liver disease. D uring: Diabetes with vasculopathy. M ay: Migraine with aura. Also contraindicated in breast feeding & post-partum females ($ Contraindications - Relative vs. Absolute vs. None Absolute Contraindication Relative Contraindication Not a Contraindication Smoker ($>35$ yrs) who quit smoking for $ Sickle Cell Disease Smoker who quit smoking for $>1$ year Person using nicotine gums Gall bladder disease Varicose veins, obesity Patient with present hepatitis (till LFT becomes normal) SLE (if lupus anticoagulant is present $\rightarrow$ absolute contraindication) Any age Females with factor-5 Leiden mutation Patients with CKD Past history of hepatitis Patients on anticoagulants (progesterone contraceptives preferred) CHD (if CHD is predisposing to thrombosis $\rightarrow$ contraindication) In females who are older & obese, progesterone-only pills are preferred. Return of Fertility Fertility returns within 3 months of stopping the pills. OCPs are Contraceptives of Choice For Newly married couples staying together. After hydatidiform mole evacuation. For spacing of pregnancy. Contraceptive Rings Other E and P containing contraceptives: RINGS Advantages over pills: Less estrogen exposure, less breakthrough bleeding. Nuva Ring $54$ mm diam, $4$ mm thick. Insert on day 1 of cycle. Composition: EE ($15 \mu g$/d), Etonorgestrel ($120 \mu g$/d). Use same ring for 3 weeks, then remove. After 1 week, insert a new ring within 3 hours of the stipulated time. Annovera Ring Composition: EE ($13 \mu g$/d), Segesterol acetate ($150 \mu g$/d). Use for 3 weeks and remove for 1 week $\rightarrow$ clean and reuse till 1 year. Not used in females with BMI $\ge 29$ due to risk of embolism. Important Points for Rings If a female removes ring during sexual activity and reinserts it within 3 hours: No backup contraception needed. If reinserted after 3 hours: Backup contraception needed for 48 hours. Annovera rings are specifically contraindicated in females with BMI $\ge 29$. Transdermal Patch Composition: EE ($20 \mu g$/d), Norelgestromin ($150 \mu g$/d). Apply new patch every week for 3 weeks (on same day, not same site, not same time). 1 week patch-free. Site: Lower abdomen, upper outer arm, buttock, upper torso, not breast. Bathing, swimming, sauna, etc. do not lead to patch removal. Patch Detachment If occurs $ If occurs $>24$ hours: New patch, new cycle begins, backup needed for 48 hours. Only Progesterone Contraceptives Types Progesterone Only Pills (POPs) / Minipill: Progesterone Implants: Implanon. Progesterone Injection: Depot Medroxyprogesterone Acetate (DMPA). Progesterone Containing IUCD: Mirena. Mechanism of Action POPs: Thicken cervical mucus. Implants, injections, Cerazette (POP available in India): Main mechanism is Anovulation. Other mechanisms: Thicken cervical mucus and inhibit tubal peristalsis. Sperms cannot penetrate the thickened cervical mucus $\rightarrow$ Decrease the chance of Pelvic Inflammatory Diseases, Sexually Transmitted Diseases, and ectopic pregnancy. Also decrease tubal peristalsis. Failure of contraception leads to increased chances of ectopic pregnancy. Absolute risk decreases but relative risk increases. Progesterone Containing Contraceptives Do Not Have Any Effect On Carbohydrate metabolism. Lipid metabolism. Clotting factors. Breast milk. These Contraceptives Can Be Used By Breast feeding females. Females with history of thromboembolism. Smokers. Age $>35$ years. Obese females. Hypertension and increased cholesterol. SLE on anticoagulant therapy. Diabetes with vascular disease. DMPA, implants and Mirena can also be used to treat dysmenorrhea due to endometriosis. Absolute Contraindications for All Progesterone Containing Contraceptives Undiagnosed vaginal bleeding. Pregnancy. Known or suspected breast cancer. Benign or malignant liver tumors. Previous history of ectopic pregnancy and PID are not a contraindication for POP, injections, or implants. Most common side effect: Irregular bleeding, mostly scanty bleeding, which may ultimately lead to secondary amenorrhea (causes endometrial atrophy). Progesterone Only Pills (POPs) Contain low dose of progesterone. Mechanism of action: Cervical mucus thickening. Cerazette: Minipill available in India. $75 \mu g$ of Desogestrel. Acts by causing anovulation. POPs must be taken at the same time every day, window period is 3 hours. Cerazette has a window period of 12 hours. Starting POPs Day 1 of menses (no backup needed). Quick start (from any day of the cycle, backup of 2 days needed). Missed Pills If one pill is forgotten or window period is crossed: Resume as soon as possible and backup contraception for 2 days. If 2 or more pills are forgotten: Stop pills for present cycle and restart once menses occurs. If no bleeding in 4-6 weeks, do urine pregnancy test. Clinical Decision to Use Minipill Contraceptive of choice in lactating females. Females over the age of 40 years. Failure Rate Typical use: $3\%$ Perfect use: $0.5\%$ Implants Single rod implant called Implanon. If implant contains barium sulphate, it's called Nexplanon. Dimensions: $40$ mm $\times 20$ mm. Core: Etonorgestrel + Barium sulphate + Ethylene vinyl acetate. Etonorgestrel $68$ mg present. Rate of release: $60 \mu g$/day (gradually decreases). Life span: 3 years. If inserted within 7 days of menstrual cycle: No backup needed, acts immediately. If inserted after 7 days: Backup needed for 3 days (or 7 days). Insertion OPD procedure under local anesthesia. Inserted on medial side of non-dominant arm with inserter. Removal OPD procedure under local anesthesia. Small incision must be made. Contraindications Same as all progesterone containing contraceptives. Not contraindicated in: Severe acne. Severe vascular/migraine headache. Severe depression. Return of Fertility After removal, fertility returns in a month. Fertility rate for implant: $0.05\%$ (most effective contraceptive). Fertility rate for Nexplanon: $0.01\%$. DMPA (Depot Medroxyprogesterone Acetate) Injection. Included as Antara in National Family Planning Program. Composition: $150 \mu g$ of MPA. Injection taken once in 3 months. Given in deltoid or gluteal region, intramuscularly. Repeated every 3 months. Window period: 4 weeks. Delay in Taking DMPA If delay of $\ge 2-4$ weeks: First perform a UPT. If pregnancy is ruled out: Inject DMPA and give backup of 7 days. Mechanism of Action Anovulation. Most common side effect: Irregular bleeding. Contraindications: Same as all progesterone containing contraceptives. Given within 7 days of LMP and is effective within 24 hours. Advantages Decrease seizure frequency. Decrease sickling in sickle cell anemia. Contraceptive of choice in epilepsy patients: DMPA. Contraceptive of choice in sickle cell anemia patients: DMPA. Disadvantages Delayed return of fertility (12-24 months). Decreases bone mineral density. Not given to breast feeding females $ Subcutaneous DMPA Prefilled syringe, dose of $104 \mu g$ of MPA. Patient can self-administer this injection subcutaneously. Repeated every 3 months. Failure Rate With perfect use: $0.3\%$. With typical use: $3\%$.