Female sex hormones: Oestrogens

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Female sex hormonesOestrogens
By C.Adithan
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Female sex hormones

• Oestrogens
• Synthesis secretion
• Regulation
• Pharmacological actions
• Pharmacokinetics
• Preparations
• Therapeutic uses
• Adverse effects
• Anti-Oestrogens
• Clomiphene citrate
• Cyclofenil
• Tamoxifen citrate
• Raloxifene
• Ormeloxifene

• Progestrogens
• Synthesis secretion
• Regulation
• Pharmacological actions
• Pharmacokinetics
• Preparations
• Therapeutic uses
• Adverse effects
• Anti-progestrogens
• Mifepristone

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Cholesterol
Oestriol
17-a- Hydroxy pregnenolone
Dehydro-epi androsterone
Pregnenolone
Andro-stenedione
Progesterone
17- Hydroxy progesterone
Oestrone
Premenopausal ovaries (10-100
µg) Postmenopasual adipose tissue(2-10
µg) Pregnancy placenta (up to
30mg)
OESTRADIOL
TESTOSTERONE
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Oestrogen
Progesterone
LH
FSH
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Oestrogens

• Natural
• Oestradiol
• Oestrone
• Oestriol

• Synthetic
• 1.Steroidal
• Ethinyl oestradiol
• Mestranol
• Tibolone
• 2.Non-steroidal
• Diethylstilbesterol
• Hexestrol
• Dienestrol
• Chlortrianisene

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Pharmacokinetics

• Absorption
• Well absorbed by oral, parenteral transdermal
  admn.
• Oestradiol undergoes high first pass metabolism.
  Therefore other synthetic preparations are more
  commonly used.
• Oestradiol esters i.m. admn. Slowly absorbed
  prolonged action
• Transport highly protein bound (SSBG,albumin)
• Metabolism
• by liver enzymes
• Significant entero-hepatic circulation
• excretion by urine after conjugation

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Oestrogen preparations

• Oral
• Conjugated oestrogen
• (0.625, 1.25 mg tab., 25 mg inj)
• Ethinyl oestradiol(0.01, 0.5,0.1mg)
• Mestranol (0.1 mg tab)
• Oesradiol succinate (1, 2 mg tab.)
• intramuscular
• Oestradiol benzoate (5, 10 mg inj.)
• Intravenous
• Fosfestrol tetrasodium
• (60 mg/ml inj, 120 mg tab)

• Topical
• Dienestrol 0.01 vaginal cream
• Transdermal
• Oestradiol (25,50 or 100 mcg/24 h)
• Oestradiol norethisterone
• (50 mcg 0.25mg)

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Oestrogens Actions
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Oestrogens Actions

• Metabolic Effects
• Anabolic effect (weak)
• Fusion of epiphysis
• Salt water retention
• B.P.
• Impaired glucose tolerance
• Blood coagulability
• HDL LDL
• Cholesterol content of bile
• Thyroxine cortisol binding globulins
• Carcinogenic Action

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Adverse effects of Oestrogen

• Nausea, anorexia, vomiting, diarrohoea
• Libido, gyaecomastia feminization (male)
• Stunted growth
• Adenocarcinoma of vagina cervix (
  offspring)
• Postmenopausal endometrial cancer
• Premenopausal Ca. breast
• Coronary thrombo-embolic disorders
• Gall stone
• Benign hepatoma
• LDL and HDL TG, hyperglycaemia

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Clinical uses of Oestrogens

• Substitution therapy
• menopausal syndrome
• Senile vaginitis
• delayed puberty
• as oral contraceptive steroids
• dysmenorrhea
• dysfunctional uterine bleeding

• acne
• hirsutism
• osteoporosis
• prevention of heart attacks
• Ca. of breast
• Ca. of prostate
• postpartum lactation

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Hormone Replacement Therapy

• Benefits
• Relief of hot flushes vasomotor symptoms
• Cardio-protection
• Osteoporosis
• Alzheimers disease

• Drawbacks
• endometrial bone
• cancer
• thromboembolic
• diseases

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Tibolone

• 19- norsteroidal drug
• Oestrogen progesterone weak androgen
• Preparation 2.5mg tab.
• Use HRT (menopausal symptoms, urogenital
  atrophy, psychological symptoms, libido and
  osteoporosis improved)
• ADR weight gain, increased facial hair,
  occasional vaginal
• spotting
• C/I hormone dependent malignancy of breast,
  uterus, undiagnosed vaginal bleeding,
  thromboembolic disease, svere liver disease,
  migraine, epilepsy

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Antioestrogens

• Anti-Oestrogens
• Clomiphene citrate
• Cyclofenil
• SERM
• Tamoxifen citrate
• Raloxifene
• Ormeloxifene

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Clomiphene Citrate

• Non-steroidal
• Blocks oestrogen receptor
• Mechanism
• GnRH Gn release
• Uses
• Sterility
• Ca. breast
• In vitro fertilization
• Male infertility

• ADME
• p.o. good absorption
• t½ 5 7 days
• adipose tissue
• Side effects
• Polycystic ovary, multiple pregnancy, hot
  flashes, gastric upset, vertigo,
  dermatitis

Cyclofenil similar to clomiphene but no
peripheral
anti-oestrogenic effects
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Tamoxifen citrate

• predominantly estrogenic partial
  anti-estrogenic action
• proliferation of breast cancer
• cells and endometrial cancer
• Anti resorptive
• total cholesterol and LDL
• No change in HDL and TGs
• risk of DVT pulmonary embolism

• Given orally
• Metabolised in liver to a more potent 4
  OH-tamoxifen
• Undergoes enterohepatic circulation
• Uses
• Palliative therapy for advanced CA Breast
• Hormonal treatment for both early and advanced CA
  Breast in women of all ages
• Adverse effects
• Hot flushes, vaginal discharge, cataract, nausea

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Tamoxifen citrate
Response rate ER ve 50 ER PR ve 60-70 ER
ve 10
For 5 years Recurrence by 47 50 Death
26 -28 Contralateral Ca. breast 47
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Raloxifene

• Bone CVS partial agonist
• Endometrium breast antagonist
• Postmenopausal women prevents bone loss
• Reduce LDL cholesterol
• 65 reduction in risk of breast cancer
• No increased risk of endometrial cancer
• No relief of vasomotor symptoms

• 60 mg tab Orally absorbed
• high first pass metabolism
• Side effects 3 fold increase in deep vein
  thrombosis pulmonary embolism (same as
  oestrogen HRT)

• Effective alternative to HRT
• for prevention of and treatment
• of osteoporosis

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Ormeloxifene

• Endometrium breast antagonist
• Excessive bleeding with anovulatory cycle at
• menopause is regularized.
• But vaginal epithelium cervical mucus is not
  altered.
• Used for treatment of DUB
• 60 mg tab
• 120 mg twice a week for 2-3 months
• Side effects
• nausea, headache, fluid retention,
• wt. gain, rise in BP, prolonged menstrual
  cycle

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Progesterone