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Clinical uses of Oestrogens

Clinical uses of Oestrogens. 1. Hormone Replacement Therapy [ HRT ] For Menopause [OE alone or with a Prog] 2. Oral Contraception [OE with a Prog] 3. Dysmenorrhoea [OE with Prog - most OCs effective]

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Clinical uses of Oestrogens

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  1. Clinical uses of Oestrogens 1. Hormone Replacement Therapy [ HRT ] For Menopause [OE alone or with a Prog] 2. Oral Contraception [OE with a Prog] 3. Dysmenorrhoea [OE with Prog - most OCs effective] 4. Dysfunctional Uterine Bleeding [DUB] [OE with a Prog -cyclically] 5. Acne [OE with a Prog - cyclically] 6. Evaluation of ovarian function [OE with a Prog - cyclically] 7. Failure Of Ovarian Development /Turner’s Syndrome [OE alone or with a Prog] Other use 8. Prostate Carcinoma [To inhibit Gn Release ] [OE alone] ________________________________________________________________________________ OE = Oestrogen Prog = Progestogen Gn = Gonadotrophin

  2. Clinical uses of Progestogens 1 HRT / OCs / Dysmenorrhoea [With OE] 2.Endometriosis [Medroxyprogesterone 2.5 -10 mg or Norethisterone 5-10 mg / day for 6-9months. Long acting medroxyprogesterone injection [effective for 12 wk] also used. 3.Threatened / Habitual abortion [Doubtful efficacy] 4.Evaluation of ovarian function[Used in the past] 5.Pregnancy diagnosis [Used in the past] 6.Inhibition of lactation [Bromocriptine preferred]

  3. HRT for Menopause Indications: (a) To relieve: Symptoms of hot flushes, Atrophic vaginitis Pruritis/Kraurosis vulvae Urethritis (b) To prevent: Atherosclerosis [Doubtful] Osteoporosis / Early Bone loss Hysterectomized [Treatment may be started on any day of MC] - OE alone Continuously Intact uterus [4 wk cycle] [a] OE alone First 14 days OE + Prog Next 14 days [b] OE + Prog. [Low doses] continuously -If not menstruating Treatment may be started on any day. -If Menstruating Treatment may be started on day 1 (or 5) of the cycle. [OE alone increases Risk of Endometrial Carcinoma With Prog. Risk but of Breast Carcinoma ] _______________________________________________________________________________________ OE = Oestrogen Prog= Progestogen MC = Menstrual cycle -Hormones taken orally /skin patch but treatment must be started with minimum effective dose. -Treatment given from a few months to few years. -OE or OE+ Prog combined patch is effective for 3- 4 days.

  4. Steroids for HRT of Menopause Oestrogens (1)Steroids Natural Oestradiol -17ß, Oestriol Oestrone + Equilin [Conjugated Oestrogens] Synthetic Ethinyloestradiol Mestranol (2)Non-Steroids Dehydrostilboestrol [Dienoestrol] Diethylstilboestrol [Stilboestrol] Given orally / skin patch/ vaginal cream _____________ Progestogens [ All Steroids] Natural Progesterone Synthetic (a)1st Generation* Dehydroprogesterone [Dydrogesterone] Medroxyprogesterone (b) 2nd Generation** Norethisterone Norgestrel ___________________________________________________________________ *Selective but week progestogens ; week androgens **Non-selective but potent ; moderate androgens

  5. HRT- Side Effects of Oestrogens/ Progestogens GID, Induce or enhance symptoms of Diabetes mellitus Risk of : -Intravascular coagulation -Endometrial carcinoma [with OE alone] -Breast / Liver carcinoma [with prolonged use] -Carcinoma in children of mothers given OE in pregnancy [Breast, uterus, testis, kidney] Contraindications Pregnancy Undiagnosed Vaginal Bleeding Thromboembolic disease Severe cardiac / hepatic / renal disease Genital tact Malignancy Precautions History of Thromboembolism Inherited Liver disorders [Dubin Johnson / Rotor-Syn.] _____________________________________________________________________ GID = Gastrointestinal disturbances- [nausea, vomiting, epigastric distress /pain]

  6. Other agents for HRT/Osteoporosis • Gonadomimetic agents (1) Tibolone A steroid with Prog / OE & weak androgenic activity GnRH Release by Stabilising Hypothalamus / Pituitary axis [Helps to reduce menopause related GnRH increase] SE: GID / dizziness / vaginal bleeding / rarely thromboembolism.

  7. Other agents for HRT / Osteoporosis [contd.] 2-Selective Oestrogen Receptor Modulator [SERM] - Raloxifene -Selective agonist of OE receptors [ERa] [in bone tissue] -Non-Significant effect on OE receptors in other body tissues [uterus / breast / hypothalamus] Use Prevention and treatment of osteoporosis in Post menopausal women. [given orally ] SE Hot flushes / Leg cramps / Oedema [Not recommended in women of child bearing age] _________________________________________________________________________________________ Other OE receptors [ERb] Ovaries, Prostate, Lungs, CNS, Blood vessels [ERg] Various tissues: Role unknown

  8. Methods for oral / long term contraception (a) Oral Contraceptives 1.Combined Pill [Combination Pill / OE + Prog] Monophasic [ same preparation for 21 days] Diphasic [ Prog content Doubled after 1wk and maintained Triphasic [ Prog content increased by 50-60% after 5-7 days and maintained In some preparations OE content is also slightly varied. 2.Sequential OE 1-14 days of M.C [ up to 16 days] OE + Prog 15-21 days of M.C [ up to 20days] 3.Progestogen only [Mini pill] Low dose Prog 4.Post-coital [Vacation Pill] on day 1 of M.C & continued without break. Prog OE OE + Prog Danazol 5.Once a month combined pill [Quinesterol 3 mg + Norethynodrel 12 mg] ________________________________________________ (b) Long Term Parenteral Contraceptives Deep I.M Medroxyprogesterone S.C. Implant Etonogestrel Intrauterine Levonorgestrel ________________________________________________________________________ M.C = Menstrual cycle S.C = Subcutaneous

  9. Other Agents For Menopausal Osteoporosis [Agents Preventing Bone Loss] [a] - Bisphonates[Etidronate / Clodronate / Pamidronate/ Risedronate] Act by Oteoclast activity SE GID / Paraesthesia Ca++ PTH in blood Liver function -with Clodronate Lymphocyte Count -with Pamidronate Flue-like symptoms -with Risedronate [b] - Salcatonin [Synthetic Calcitonin] Act by Bone Resorption [Counteracts PTH effect & reduces osteoclastic activity] SE GID / Paraesthesia [c] - Calcium salts / Vitamin D ____________________________________________________________________________________________ GID = Gastrointestinal disturbances [nausea, vomiting, epigastric distress/pain]

  10. Commonly used Steroids for Oral Contraception Oestrogens Ethinyloestradiol Mestranol Progestogens I Generation [Selective but week receptor action] Now mainly used for HRT] Dydrogesterone Medroxyprogesterone II Generation [Non-selective but potent receptor action: Moderate androgens] Norethisterone Norgestrel Norgestimate III Generation* [Non-selective but potent receptor action: week androgens] Gestodene Desogestrel Etonogestrel ____________________________________________________________________________________ *Risk of androgen SE reduced but of venous thromboembolism & MI are somewhat increased

  11. OCs Possible modes of action OE + Prog  Gn Release  Ovulation (99%) Interference in Ovum / Blastocyst transport  Implantation [Endometrium hypoplastic / out of phase] OE alone Corpus Luteum degeneration FSH secretion Prog. Alone  Cervical mucus hostility towards spermatozoa  Uterine pH and  sperm motility  Sperm Capicitation  Ovarian endothelial cell activity.

  12. Minor Side Effects of Oral Contraceptives (a) High OE / Low Prog GID, Dysmenorrhoea, Menorrhagia, Enlargement of uterus / Breast Chloasma, Telangiectasia Oedema, Visual disturbances Redistribution of Fat (b) Low OE / High Prog Redistribution of fat Irritability, headache, depressed mood, fatigue Dry vagina, Moniliasis / Breakthrough bleeding Breast tenderness, Carbohydrate intolerance Increased appetite / weight Acne, oily scalp, alopecia / CHO- intolerance Cholestatic hepatitis / Increased BP

  13. Contraindications / Precautions / Risk factors for OCs Absolute contraindications Pregnancy Thromboembolism, Cerebrovascular /Coronary artery Disease Impaired liver function, Hepatic adenoma Undiagnosed vaginal bleeding Breast or other malignancies Relative contraindications Within 2 wk of pregnancy termination Diastolic pressure >110 / vascular or migraine headaches Cardiac or renal disease / Diabetes mellitus Gall Bladder disease Epilepsy Fibrocytic disease Heavy smokers Planned operation in next 6 wk / patients in leg casts Risk of side effects increased in Smokers >35 Yr Obese History of Preeclampsia Hypertension _______________________________________________________________________ Stop pill 6 weeks prior to major surgery.

  14. Prevention Of Pregnancy After Missing A combined Pill < 12 hr Take the missed pill immediately and further pills as normal > 12 hr Take the most recent pill but discard other missed pills If the number of pills [after the most recent pills] is < 7 Start the next packet without break If the number of pills [after the most recent pills] is > 7 Start the next packet after 1 wk break ___________________________________________________________________ Use extra precautions for the next 7 days

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