Progesterone & oral contraceptives

Pharmacology PPT

1. Progesterone & Oral contraceptives Dr Chintan Doshi

2. Pharmacokinetics Active orally bioavailability is only 25%. Largely metabolized in liver by CYP 3A4 Excreted in bile t½:20–36 hr. Interaction with CYP 3A4 inhibitors

3. Uses Termination of pregnancy up to 7 weeks 600 mg as single oral dose follow it up 48 hours later by a single 400 mg oral dose of misoprostol Cervical ripening Before attempting surgical abortion or induction of labour Postcoital contraceptive Mifepristone 600 mg given within 72 hr of intercourse

4. Contd. Once-a-month contraceptive Induction of labour Cushing’s syndrome Endometriosis Uterine fibroid Certain breast cancers Meningioma

5. Introduction Progestin used in OC pills are Norethisterone Norgestrel or levonogestrol 19-nontestosterone Derivatives- Desogestrel Gestodene Norgestimate Drospirenone (DRSP) – derived from 17-alpha spironolactone.

6. Introduction cont… Norgestimate and desogestrel have been shown to have little or no androgenic activity. Drospirenone has antiandrogenic and antimineralocorticoid activities.

7. Types Hormonal oral contraception Combined oral contraceptives Progesterone only contraceptives Non hormonal oral contraception Ormeloxifen( centchroman)

8. Monophasic Fixed amount of estrogen and progestin Taken for 21 days 7- days pill free

9. Biphasic each tablet contains a fixed amount of estrogen, amount of progestin increases in the second half of the cycle; 2. Triphasic the amount of estrogen may be fixed or variable, while the amount of progestin increases in 3 equal phases. Multiphasic COC

10. MECHANISM OF ACTION The combined OC’s multiple mechanisms of action may contribute to its high efficacy.

11. MECHANISM OF ACTION Suppress gonadotropin secretion, thereby inhibiting ovulation. Progestin reduces frequency of LH secretory pulse. Estrogen reduces FSH secretion. Both synergies to inhibit midcycle LH Surge. As a result follicle fails to develop and fails to rupture.

12. Other mechanisms of action include: Development of endometrial atrophy, making the endometrium unreceptive to implantation Production of viscous cervical mucus that impedes sperm transport Possible effect on secretion and peristalsis within the fallopian tube, which interferes with ovum and sperm transport The postcoital pill may dislodge a just implanted blastocyst or may interfere with fertilization/implantation .

13. Side effects A. Nonserious side effects Nausea and vomiting Headache Breakthrough bleeding Breast discomfort B. Side effects that appear later Weight gain, acne and increased body hair Chloasma Pruritus vulvae

14. Contd. 4.Carbohydrate intolerance 5.Mood swings C. Serious complications Leg vein thrombosis and pulmonary embolism Coronary and cerebral thrombosis Rise in BP Genital carcinoma: vaginal, cervical, and breast cancers Benign hepatomas Gallstones

15. Contraindications Absolute Thromboembolic , coronary and cerebrovascular disease or a history of it Moderate-to-severe hypertension; hyperlipidaemia . Active liver disease, hepatoma or h/o jaundice during past pregnancy Suspected/overt malignancy of genitals/ breast Prophyria Impending major surgery

16. Relative contraindications 1. Diabetes: control may be vitiated. 2. Obesity 3. Smoking 4. Undiagnosed vaginal bleeding 5. Uterine leiomyoma : may enlarge with estrogenic preparations; progestin only pills can be used. 6. Mentally ill 7. Age above 35 years 8. Mild hypertension 9. Migraine 10. Gallbladder disease

17. Non contraceptive benefits -OCP Cycle-related: Irregular cycles, dysmenorrhea , menorrhagia &anemia Functional ovarian cysts Prevention of: Bone loss Fibrocystic/benign breast disease Pelvic inflammatory disease (PID), Ectopic pregnancy Treatment of: Acne, Hirsuitism Perimenopausal symptoms

18. Progesterone Only Pill contain only synthetic progestogens (progestins) known as mini pills. taken daily without interruption

19. Preparation 350 µg norethindrone 30 µg levonorgestrel 75 µg desogestrel 75 µg norgestrel

20. POP - Advantage Not associated with increased risks of DVT or heart disease decreased clotting risk, they are not contraindicated in the setting of sickle-cell disease Recommended over regular birth control pills for women who are breastfeeding because the mini-pill does not affect milk production

21. POP - Disadvantage Episodes of irregular, unpredictable spotting Breakthrough bleeding :Major reason women discontinue use of progestin-only contraceptives. Mastalgia (breast tenderness) or mood swings.

22. Non Hormonal Contraception Centchroman

23. Centchroman Developed by Central drug Research Institute (CDRI), Lucknow Introduced in 1991, Saheli world’s first non-steroidal oral contraceptive pill. Composition: Each tablet contains centchroman 30 mg.

24. Mechanism of Action Weak estrogenic and potent anti estrogenic Acts as anti- implantation agent by inducing embryo-uterine asynchrony, accelerated tubal transport and suppression of decidualization

25. Dosage 30 mg twice a week on fixed days for the first three months followed by one pill in a week thereafter.

26. Side effects The only side effects reported with Centchroman - delay in the menstrual cycles in around 6-8% of the cases.

27. Advantage No hormonal side effects No teratogenic, mutagenic or carcinogenic effect does not cause nausea, vomiting, dizziness and break through bleeding and no adverse effect on lipid profile

28. Emergency Contraception Therapy used to prevent pregnancy after an unprotected or inadequately protected act of sexual intercourse.

29. Yuzpe method Levonogestrol 0.5 mg + ethinylestradiol 0.1 mg, two doses at 12 hour interval within 72 hours of exposure Ulipristal 30 mg single dose as soon as possible, but within 120 hours of intercourse Mifepristone 600 mg single dose taken within 72 hours of intercourse.

30. THANK YOU