Clinical uses of Oestrogens / Progestogens
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
6.
Evaluation of ovarian function
[OE with a Prog - cyclically]
[OE with a Prog - cyclically]
7.
Failure Of Ovarian Development / Turner’s Syndrome
[OE alone or with a Prog]
8.
Prostate Carcinoma [OE to inhibit Gn Release]
9.
Acne with a Prog - cyclically]
________________________________________________________________
OE = Oestrogen; Prog
= Progestogen
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
OE + Prog
First 14 days
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 is reduced but of Breast Carcinoma is increased ]
__________________________________________________
OE
=
Oestrogen
Prog. =
Progestogen
MC =
Menstrual cycle
-Hormones taken orally/skin patch but treatment must be started with minimum
effective dose.
-Treatment given from few months to few years.
-OE / OE+ Prog. combined patch is effective for 3-4 days.
Steroids for HRT of Menopause
Oestrogens@
(a)
(b)
@
Steroids
Natural
Oestradiol -17ß,
Oestriol
Oestrone + Equilin [Conjugated Oestrogens]
Synthetic
Ethinyloestradiol
Mestranol
Non-Steroids
Dehydrostilboestrol [Dienoestrol]
Diethylstilboestrol [Stilboestrol]
Given orally / skin patch / vaginal cream
_____________
Progestogens
Natural
Progesterone
Synthetic
1st Generation*
2nd Generation**
Dehydroprogesterone [Dydrogesterone]
Medroxyprogesterone
Norethisterone
Norgestrel
________________________________________________________________
*Selective but week progestogens; week androgens
**Non-selective but potent; moderate androgens
HRT- Side Effects of Oestrogens/ Progestogens
GID,
Induce / 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]
Other agents for HRT / Osteoporosis
1 Tibolone
A steroid with progesterone / OE / weak androgen activity
GnRH Release by Stabilising Hypothalamus / Pituitary axis
[Helps to reduce menopause related GnRH increase]
SE
GID/ dizziness /vaginal bleeding / rarely thromboembolism
2 - Raloxifene - SERM [Selective Oestrogen Receptor Modulator]
-Selective agonist of OE receptors [ER [in bone tissue]
-Non-Significant effect on OE receptors in other body tissues
[uterus / breast/Hypothalamus]
Use
Prevention and treatment of osteoporosis in postmenopausal women
[Given orally]
SE
Hot flushes / Leg cramps / Oedema
[Not recommended in women with child bearing age]
Other agents for menopausal osteoporosis [agents preventing
bone loss]
[a] - Bisphonates [Etidronate / Clodronate / Pamidronate/
Risedronate]
Act by inhibiting Oteolcast activity
SE
GID / Paraesthesia,
Ca++
PTH in blood.
Liver Function
-with Clodronate
Lymphocyte Count
-with Pamidronate
Flue-like symptoms
- with Risedronate
[b] - Salcatonin [Synthetic or Salmon Calcitonin]
Act by
Bone Resorption :
SE GID / Paraesthesia
[c] - Calcium salts / Vitamin D
Other uses of Oestrogens/ Progestogens
(2)
Oral Contraceptives
Types
1 - Combined pill
[Combination pill] OE + Prog]
Started on day 1 [or 5] of M.C for 21 days
[Placebo / No drug until next M.C]
a- Monophasic [Same preparation for 21 days]
B- Diphasic
maintained]
c- Triphasic
[PROG. content doubled after 1 week and
[PROG. content increased by 50-60% after 57 day
with a similar increase after next 5-7 days and
maintained
In some preparations OE content is also slightly varied
2- Sequential
OE 1 -14 days of M.C [upto 16]
OE + PROG 15 -21 days of M.C [upto 20]
[No drug until next M.C]
_________________________________________________
OE = Oestrogen; Prog = Progestogen; M.C = Menstrual cycle
Oral contraceptives [contd.]
(3) Progesterone only [Mini pill]
Low dose Prog on day 1 of any M.C
Continued without break
__________________________________________
(4) Post-coital
[Vacation pill]
Prog within 8 hr
OE
[up to 24 hr]
within 24 hr [up to 72 hr
OE +PROG within 24 hr [72 hr]
[single dose]
[5 days]
[1-2 days]
Danazol may also be effective within 72 hr
(4) Once a month combined pill
[Example Quinesterol 3mg + Norethynodrel 12 mg]
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.
Irritability, Headache, Depressed mood, Fatigue
Dry vagina, moniliasis / breakthrough bleeding
Alopacia
Carbohydrate intolerance
Breast tenderness / increased appetite / weight
Acne, oily scalp, alopecia / CHO intolerance
Colestatic hepatitis / Increased BP
Major side effects of oral contraceptives
Venous embolism, IHD , MCI
Increased BP / Subarachnoid haemorrhage / Stroke
Acute hepatitis
Tumours - Carcinoma of breast / cervix / liver adenoma
Teratogenicity if given in pregnancy