Clinical uses of oestrogens
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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
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


Clinical uses of progestogens
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]


Hrt for menopause
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.


Steroids for hrt of menopause
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


Hrt side effects of oestrogens progestogens
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]


Other agents for hrt osteoporosis
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.


Other agents for hrt osteoporosis contd
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


Methods for oral long term contraception
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


Other agents for menopausal osteoporosis agents preventing bone loss
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]


Commonly used steroids for oral contraception
Commonly used Steroids for Oral Contraception Bone Loss]

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


Ocs possible modes of action
OCs Possible modes of action Bone Loss]

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.


Minor side effects of oral contraceptives
Minor Side Effects of Oral Contraceptives Bone Loss]

(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


Contraindications precautions risk factors for ocs
Contraindications / Precautions / Risk factors for OCs Bone Loss]

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.


Prevention of pregnancy after missing a combined pill
Prevention Of Pregnancy After Missing A combined Pill Bone Loss]

< 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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