Clinical uses of Oestrogens

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 /Turners
  Syndrome OE alone or with a Prog
• Other use
• 8. Prostate Carcinoma To inhibit Gn Release
  OE alone

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.

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

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

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

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

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

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 gt110 / 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

14
Prevention Of Pregnancy After Missing A combined
Pill

• lt 12 hr Take the missed pill immediately and
  further pills as normal
• gt 12 hr Take the most recent pill but discard
  other missed pills
• If the number of pills after the most recent
  pills is lt 7
• Start the next packet without break
• If the number of pills after the most recent
  pills is gt 7
• Start the next packet after 1 wk break
• __________________________________________________
  _________________
• Use extra precautions for the next 7 days