Conjugated Oestrogens

Registered South African indications: 

• Vaginitis
• Atrophic changes in vulval epithelium
• Dyspareunia
• Prior to pelvic plastic surgery

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hepatic impairment
• Undiagnosed abnormal genital bleeding
• Thrombosis or history thereof
• Active or history of arterial thromboembolic disease 
• Breast cancer or history thereof
• Oestrogen-dependent tumour
• Known protein C, protein S, antithrombin deficiency or other known thrombophilic disorders

Cautions

• Breastfeeding
• Renal impairment
• Endometriosis
• Inherited thrombophilia
• Preexisting hypertriglyceridemia
• Family history of ovarian cancer
• Asthma
• Carbohydrate intolerance
• Cardiovascular disease
• Diabetes mellitus
• Hypercholesterolemia
• Hypertension
• Systemic lupus erythematosis
• Obesity
• Smoking
• History of venous thromboembolism
• Epilepsy
• Gallbladder disease
• Hepatic hemangiomas
• Hypoparathyroidism
• Migraine
• Porphyria
• Thyroid dysfunction
• Concomitant use with barrier contraceptives

Forms avail. in SA and covered in this monograph: cre

Vulvovaginitis
-Postmenopausal and senile vulvovaginitis
Atrophic vaginitis
Pruritus vulvae 
Dyspareunia 
-Associated with an atrophic vaginal epithelium
Prior to plastic pelvic surgery in menopausal cases

• Topical (cre): 0.5-2g, dly, intravaginally

Administration should be cyclic (e.g., three weeks on and one week off) and for short use only

Attempts to discontinue or taper medication should be made at 3-6 month intervals

Not established for use in children

Pregnancy

• Not indicated during pregnancy
• If pregnancy occurs during medication with conjugated oestrogens treatment should be withdrawn immediately. The results of most epidemiological studies to date relevant to inadvertent foetal exposure to estrogens indicate no teratogenic or foetotoxic effects

Breastfeeding

• Caution; not recommended
• Conjugated oestrogens are not indicated during breastfeeding

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Contraindicated

Elderly

• No dose adjustment recommended
  The lowest effective dose should be used

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Dizziness
• Headache
• Migraine
• Nervousness
• Cerebrovascular accident/ stroke
• Exacerbation of chorea
• Changes in libido
• Mood disturbances
• Depression
• Irritability
• Dementia

Cardiovascular Disorders

• Pulmonary embolism
• Venous thromboembolism
• Venous thrombosis
• Myocardial infarction
• Increases in blood pressure

Gastrointestinal Disorders

• Nausea and vomiting
• Bloating
• Abdominal pain
• Pancreatitis
• Ischaemic colitis

Hepatobiliary Disorders

• Gallbladder disease
• Cholestatic jaundice

Genitourinary Disorders

• Breakthrough bleeding
• Dysmenorrhoea
• Pelvic pain 
• Breast pain
• Breast tenderness
• Breast enlargement
• Discharge
• Vulvovaginal burning
• Vulvovaginal irritation
• Genital pruritus
• Vaginal discharge
• Leukorrhoea
• Gynaecomastia in males
• Increased size of uterine leiomyomata
• Endometrial hyperplasia
• Vaginitis
• Vaginal candidiasis
• Cystitis-like syndrome

Endocrine and Metabolic Disorders

• Glucose intolerance
• Hypocalcaemia 
• Precocious puberty        
• Weight change
• Increased triglycerides

Musculoskeletal Disorders

• Arthralgias
• Leg cramps

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Chloasma
• Melasma
• Hirsutism
• Pruritus
• Rash
• Erythema multiforme
• Erythema nodosum
• Oedema

Immune, Blood and Lymphatic System Disorders

• Anaphylactic reactions
• Urticaria 
• Angioedema
• Hypersensitivity
• Breast cancer
• Ovarian cancer
• Fibrocystic breast changes
• Endometrial cancer
• Enlargement of hepatic hemangiomas 
• Growth potentiation of benign meningioma

Sensory Disorders

• Intolerance to contact lenses
• Retinal vascular thrombosis

• Thyroid replacement therapy
• Benzyl alcohol
• Anastrazole
• Anticoagulants
• CYP3A4 inducers
• Dabrafenib
• Dehydroepiandrosterone
• Enzalutamide
• Exemestane
• Hemin
• Hyaluronidase
• Ospemifene
• Pomalidomide
• Somatropin
• St John's wort
• Tipranavir
• Tizanidine

• Papanicolaou smear
• Breast examination
• Mammogram
• Blood pressure

Specific cases may require

• Endometrial sampling
• Lipid profile
• Blood glucose
• Thyroid function

The pharmacologic effects of conjugated oestrogens are similar to those of endogenous oestrogens. In responsive tissues (female urogenital organs, breasts, hypothalamus, pituitary) oestrogens enter the cell and are transported into the nucleus. As a result of oestrogenic activity, specific RNA and protein synthesis occurs. Oestrogens have many effects on lipid metabolism, the most important being the increase in high-density lipoprotein (HDL) levels and a decrease in low-density lipoprotein (LDL) values which results in a beneficial ratio of HDL to LDL. Metabolism and inactivation occur primarily in the liver. Topical conjugated equine oestrogen provides local oestrogenic activity.

Vaginal cream (per g) 0.625mg

• Premarin (Pfizer) originator

Also available in the following forms: Injection and tablet.