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HORMONAL CONTRACEPTIVES

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HORMONAL CONTRACEPTIVES

  1. 1. Dr. SHARON .D. SHEREGAR MBBS, MD (Pharmacology)
  2. 2.  Interception in the birth process at any stage ranging from ovulation to ovum implantation.  It includes all measures temporary or permanent designed to prevent pregnancy due to coital act.
  3. 3. 1) To bring down population growth 2) To reduce infant and maternal mortality rate 3) To prevent pregnancies that are too early, too frequent and too many.
  4. 4. First orally active synthetic steroidal estrogen was synthesized in 1938 by Hans Herloff & Walter Hohlweg Ethinyl estradiol & Mestranol
  5. 5.  In 1950,Pincus,Garcia and Rock found progesterone and 19- norprogestin to prevent ovulation in women.
  6. 6.  100% effective  Safe  Totally reversible  Acceptable  Inexpensive  Simple to use  Requires minimal motivation, supervision & maintenance.
  7. 7. Methods of Contraception c Natural Oral cc Injectables Gossypol Oral Injectables Implants Transdermal patch Barrier Permanent Barrier Natural Oral Permanent
  8. 8. 1.NATURAL METHODS 2.BARRIER METHODS 3.INTRAUTERINE DEVICES 4.PERMANENT
  9. 9. Oral Parenteral Devices 1.COC’s 1.Injectables 1.IUD  Monophasic -DMPA -LNG-IUS  Biphasic -NET-EN 2.Vaginal Ring  Triphasic -Combined 2.Minipill 2.Implant 3.Emergency/Post -Norplant Coital C. -Implanon 4.Centchroman 3.Transdermal patch
  10. 10. 1) Combination pills: A. Monophasic B. Biphasic C. Triphasic 2) Minipill / Progestin only pill 3) Post coital / Emergency contraception / Morning after pill 4) Centchroman
  11. 11. Estrogen (E) 1. Ethinyl estradiol - most common, Dose -0.02 to 0.05mg 2. Mestranol Progesterone (P)  19-nortestoterones: 1. Levonorgestrel 0.15 mg 2. Norethindrone 0.5 mg 3. Norgestimate 0.25 mg 4. Drosperinone Less Androgenic - Norgestimate,Desogestrel, Gestodene
  12. 12. MALA-N Estrogen (mg) Progestin (mg) Ethinyl estradiol 0.03 Norgestrel 0.30 Mala-D Ethinyl estradiol 0.03 D-Norgestrel 0.30 Ovral-28 Ethinyl estradiol 0.05 D, L-Norgestrel 0.5 Ovcon 50 Ethinyl estradiol 0.05 Norethindrone 1.0 Norinyl 1/50, Ortho-Novum 1/50 Mestranol 0.05 Norethindrone 1.0 Femilon 150ug desogestrel + 20ug EE Loette 100ug LNG + 20ug EE
  13. 13. B. Biphasic pills: They deliver the same amount of estrogen each day but level of progestin is increased about halfway through cycle Estrogen (mg) Progestin (mg) Ortho-novum 10/11 , Necon 10/11. Day 1 – 10 Ethinyl estradiol 0.035 Norethindrone 0.5mg Day 11 - 21 Ethinyl estradiol 0.035 Norethindrone 1.0mg Mircette which is biphasic, changes progeterone hormone levels twice during the 28 day pack.
  14. 14. C. Triphasic Tablets: Contain high dose of Estrogen in midcycle with increasing doses of Progestin given over 3 successive phases. Attempts to mimic the natural female cycle. DAYS ESTROGEN PROGESTERONE 1-6 Ethinylestradiol- 30microgm Norgestrel- 0.05mg 7-11 Ethinylestradiol- 40microgm Norgestrel- 0.075mg 12-21 Ethinylestradiol 30microgram Norgestrel- 0.125mg
  15. 15. Category 1: (no restriction of use) 1. Menarche to <40yrs 2. Postpartum >21 days, Post- abortion 3. Endometriosis, fibroid 4. Iron deficiency anemia
  16. 16. 1. Age over40 2. Obesity 3. Migraine 4. Valvular heart disease 5. Diabetes 6. Hyperlipidaemias
  17. 17. 1. Cigarettes smoking <15/ day in>35 years 2. Postpartum <21 days 3. Cholestatic jaundice 4. Hypertriglyceridemia
  18. 18. 1. Stroke & CAD 2. Hypertension( SBP>160 & DBP> !00) 3. Thrombotic patients 4. Suspected pregnancy 5. Breast cancer 6. Hypersensitivity to any component of pill
  19. 19.  The first pill is taken on 5th day after start of menses, thereafter, one pill is to be taken consecutively for 21days.The next 7 days are Pill Free Period’ & next course starts after 5th day of menses.
  20. 20. 20 Seasonale Seasonique Lybrel Aim • To reduce or even eliminate monthly periods and thereby prevent the pain and discomfort that often accompanies menstruation. • These oral contraceptives contain a combination of estradiol and levonorgestrel.
  21. 21. 21 SEASONALE  Got approved in 2003.  It contains 81 days of active pills followed by 7 days of inactive pills.  Women who take Seasonale have on average a period every 3 months. SEASONIQUE  84 days of levonorgestrol-estradiol pills followed by 7 days of pills that contain only low-dose estradiol
  22. 22. 22  Approved by FDA In 2007  It supplies a daily low dose of levonorgestrol and estradiol taken 365 days a year.  It completely eliminates monthly menstrual periods.
  23. 23. ▫ Prevent ovulation by inhibiting Gonadotropin secretion via pituitary & hypothalamic inhibition ▫ Progestational agent in pill ; suppresses LH secretion ▫ Estrogenic agent ; suppresses FSH secretion Failure rate: 0.5-1HWY 23 Hypothalamus Anterior pituitary LH FSH Estrogen, Progesterone GnRH LH, FSH
  24. 24. Estrogen in pill:
  25. 25. Progesterone also: 1. thickens cervical mucus and 2. Prevents passage of sperm into the uterus 3. Changes uterine lining to inhibit implantation 4. Alters secretion & peristalsis within fallopian tubes
  26. 26. Contraceptive NonContraceptive To Prevent Pregnancy
  27. 27.  Improvement in menstrual abnormalities: 1. Cycle stabilization 2. Reduction of Dysmenorrhea, Menorrhagia 3. Reduction of Premenstrual Tension Syndrome 4. Protection against Iron Deficiency Anemia  Protection against cancer:  Endometrial and Ovarian cancer: reduces risk by 40%  Protection against health diseases: 1. Pelvic Inflammatory Disease 2. Endometriosis 3. Fibroid Uterus 4. Hirsutism and acne 5. Benign breast diseases
  28. 28. Estrogen excess  Breast tenderness  Nausea, vomiting  Chloasma  Lactation suppression  headaches  Gall stones  Hypertension  Arterial & venous thrombosis  Glucose intolerance Progestin excess  Breast engorgement  Acne, oily skin, hirsutism  Weight gain  Mood swings  Increase LDL & decrease HDL
  29. 29.  They may be Mild, Moderate or Severe.  Severe A/E require cessation of therapy . Mild Adverse Effects include: 1) Nausea , breast tenderness, breakthrough bleeding 2) Headache: Often mild and transient 3) Worsening of Migraine / onset of migraine may be associated with cerebrovascular accidents. 4) Failure of withdrawal bleeding Change in the preparation or method of contraception.
  30. 30. Moderate Adverse Effects: May require discontinuation of therapy 1) Break through bleeding 2) Changes in serum lipids :Progestin HDL,  LDL , Estrogens:  HDL,  LDL. 3) Weight gain 4)  Skin Pigmentation & Hirsutism; with androgenic progestin. 5) Acne :  with androgenic progestin, improvement with estrogenic prep. 6) Vaginal infections 7) Amenorrhea.
  31. 31. Severe Adverse Effects: 1. Vascular Effects:  Venous Thromboembolic disease: DVT & Pulm Embolism  Hypertension  Myocardial Infarction  Cerebrovascular disease 2. Depression 3. Gastrointesinal Disorders 4. Others: Alopecia, Skin disorders like Erythema multiforme, Erythema nodosum .
  32. 32. 1. Anti-convulsants: barbiturates, carbamazepine,felbamate, phenobarbital, phenytoin, primidone,topiramate, vigabatrin 2. Anti-fungal: Greisofulvin 3. Anti-TB: Rifampicin 4. Antibiotics: ampicillin, amoxycillin, neomycin, nitrofurantoin, metronidazole, penicillin, chloramphenicol, tetracycline, sulfonamide, quinolones.
  33. 33. 1. Analogue of spironolactone 2. Good cycle control 3. Progestogenic activity suppress LH 4. Anti-androgenic activity- beneficial in acne, seborrhoea & hirsutism
  34. 34. 1. Progestin with anti-androgenic property & weak glucocorticoid effect 2. Useful in Poly cystic ovarian syndrome (PCOS) & Acne
  35. 35. Levonorgestrel 30 μg, norethisterone 350 μg, norgestrel 75 μg.Desogestrel (75 μg)- containing minipill (Cerazette®) POP’s must be taken at the same time every day. Good Candidate- Breastfeeding Woman
  36. 36. Lower dose of progesterone then OCPs MOA- 1.Thinning of the endometrial lining 2.Thickening of the cervical mucus 3.Slowing ovum transport through ed tubal motility 4.Inhibition of Ovulation Absolute C/I 1.Pregnancy 2.Breast cancer PROGESTIN ONLY MINIPILL A/E: The most common A/E is Episodes of unpredictable spotting & breakthrough bleeding .
  37. 37. WHO (1998) Emergency contraception can be provided using 1. Emergency contraceptive pills (ECPs) Use within 72 hours 2. Intra-uterine devices (IUDs) Inserted within 5 days and used as long term method
  38. 38. 39 Mechanism of Action:  Ovulation inhibited or delayed  Alterations in endometrial receptivity for implantation  Dislodges an implanted Blastocyst.  Production of cervical mucus that decreases sperm penetration  Alterations in tubular transport of sperm, egg or embryo
  39. 39. 1. Yuzpe regimen: a) 2 doses of COCPs containing EE 50µg& levonorgestrel250µg-in 72hrs &next after 12hrs. b) Effective-90% 2. 2 doses of levonorgestrel 0.75mg each- 1st in 48hrs & 2nd in 12hrs. EC2, Pill 72, E-Pill, Norlevo, i pill (available in India) 3. Mifepristone: 600 mg once in 72 hrs. 40
  40. 40. 41 Recently approved in 2010, ULIPRISTAL ACETATE (SPRM) in a single oral dose of 30mg is more effective if taken in 120hrs/5days. If these measures fail, pregnancy should be terminated to avoid teratogenic deformities of fetus.
  41. 41. 42  SERM, non-steroidal  Once per week, 30 mg  First 3 months - pill twice per week  Later followed by once per week  Also for treatment for DUB  Saheli, Centron & Sevista Mechanism of action • Asynchrony between ovulation & development of uterine lining • Speeds transport of egg through fallopian tubes • Implantation not possible Pearl Index - 9
  42. 42. 43 Progesterone only injectables: • Intramuscular injection DMPA: 150 mg every 3 months 300 mg every 6 months NET-EN: 200 mg every 2 months Failure rates: DMPA: 0.1/HWY NET-EN: 0.4/HWY 1992,FDA approved
  43. 43. 44  FDA approval 2004  Sustained absorption of progestin  Low dose of progestin (104 mg instead of 150 mg)  Injections every 3 months Mechanism of action: 1. Inhibits ovulation 2. Thick cervical mucus
  44. 44. 45 COMBINED INJECTABLES-Given at monthly intervals-IM • 1.Estradiol valerate5mg+17-hydroxyprogesterone caproate250mg • 2.Cyclofem/Cycloprovera/Lunelle(DMPA25mg+Estra diol cypionate5mg)Failure rate: 0.2 % • 3.Mesigyna (NET-EN + Estradiol valerate)FailureR:0.4% Mechanism of action 1. Suppresses ovulation 2. Thickening of cervical mucus 3. Reduced receptivity of endometrium to blastocyst
  45. 45. 1. Single flexible rod 4 cm long, contains 68mg of etonogestrel 2. Releases 60 µg/day for 3 yrs 3. Inhibits ovulation within 8 hrs of insertion & provides contraception for 3 years Uniplant: contains 55 mg nomegestrel acetate in a 4cm silicone capsule with 100ug release per day IMPLANTS: IMPLANON
  46. 46. Each rod measures 2.5 mm in diameter & 4.3 cm in length containing 75 mg of LNG Drawbacks IMPLANTS- Irregular bleeding Spotting Amenorrhoea Occasional removal problems Failure rate: 0.1/HWY
  47. 47.  Inserted at any time during menstrual cycle  Sub-dermally on the inner aspect of the non- dominant arm  Removal requires making 2 mm incision at distal tip of implant
  48. 48. Works trans-dermally by: 1. Combination of progestin & estrogen 2. Slowly releasing 3. Through skin Types:- 1. Patch 2. Spray-on 3. Gel 49
  49. 49.  Transdermal contraceptive patch ‘OrthoEvra’ was approved by US FDA in 1992.  Sites: Buttocks, Upper outer arm Lower abdomen, back, upper torso.
  50. 50.  3-patch system  Apply 1 patch each week for 3 weeks  Apply each patch the same day of the week  1 week is patch-free Week 1 Week 2 Week 3 Week 4 Patch #1 Patch #2 Patch #3 28-day cycle Patch-free Week 5 Start next cycle 28-day cycle
  51. 51.  Nestorone - Metered Dose Transdermal System (MDTS)  In phase I trial as of Feb 2009  Absorbed instantaneously  MDTS® daily skin spray formulations  Hormone collects as reservoir with in the skin and slowly diffuses into the blood stream
  52. 52. First generation • Inert, non medicated • Polyethylene/o ther polymers Second generation • Addition of metallic copper • Cu- anti fertility effect • Smaller devices, easier to fit Third generation • Hormone releasers Intra-Uterine Devices
  53. 53. • Third generation: Hormone releasers 1. Progestasert – 38 mg progesterone 2. Mirena/LNG IUD: - Effective life of 5 yrs - 52 mg of levonorgeterel 3. Fibroplant  LNG released@14ug/day  Suitable in peri-menopausal women.  Effective for 3 years. 54
  54. 54.  Expulsion  Uterine Perforation  Irregular bleeding  Pelvic infection  Ectopic pregnancy  Pain  Pregnancy: Failure rate in 1st year- 3%
  55. 55. The first vaginal contraceptive ring ‘NuvaRing’ was approved by FDA in 2001 & marketed in 2002 • Releases 15ug EE & 120ug etonogestrel over 24hrs
  56. 56.  Soft polymer device NuvaRing:  Monthly  Used for 21 days followed by 7 day hormone- free interval  Completely inhibits ovulation  ADRs  Vaginitis,Leucorrhoea,Headache,Expulsion 57 Failure rate: 1-2/HWY 54 mm 4 mm Vaginal ring
  57. 57. 59 Male contraception 59
  58. 58. 60 Male contraception 6060
  59. 59.  Non-steroidal  Derived from cotton seed and used in China.  Dose: 20mg/day for initial 2-3 months followed by 50-60 mg/week for not more than 2 yrs.  Mechanism Of Action: Decreases sperm count and sperm motility. 61
  60. 60. Vasectomy Tubal occlusion/Tubectomy Hysterectomy Laparotomy/Mini lap
  61. 61. 63  Desogestrel : Approved in 1998, Mircette was the first oral contraceptive to offer a low estrogen dose and a new type of dosing regimen. Some studies suggest an increased risk for blood clots with desogesterel.  Levonorgestrel : is used in Seasonale and Seasonique, as well as many other oral & non-oral contraceptives.
  62. 62. 64 86% success rate for 1st time placements of micro-inserts 3 months of alternative contraception Follow up HSG procedure
  63. 63. 65 EssureTM Micro-Insert (Approved in 2002)
  64. 64. 66  Monolithic microspheres  Steroid esters  Microspheres  Immuno-contraceptions  Sperm and Ovum Immuno-contraceptives.
  65. 65. 67 HCG IMMUNOCONTRACEPTIVES • The most advanced immuno-contraceptives are those based on hCG. • Three main types have been developed: 1. hCG-beta subunit conjugated to tetanus toxoid (hCG-TT) 2. hCG beta subunit - ovine LH alpha subunit conjugated to tetanus toxoid and diphtheria toxoid (HSD-TT-DT) 3. hCG beta subunit C-terminal 37 residue conjugated to diphtheria toxoid (CTP-DT).
  66. 66. THANK YOU

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