Preparations and Dose - Estrogen

PREPARATIONS AND DOSE

All estrogen preparations have similar action. Their equivalent parenteral doses are—

Estradiol 0.1 mg = Ethinylestradiol 0.1 mg = Mestranol 0.15 mg = Conjugated estrogens 10 mg = Estriol succinate 16 mg = Diethylstilbestrol 10 mg.

The oral potencies differ from the above due to differing extents of first pass metabolism. Estradiol is inactive orally, conjugated estrogens and estriol succinate undergo partial presystemic metabolism, while in case of ethinylestradiol, mestranol and diethylstilbestrol the oral and parenteral doses are practically the same.

The preferred route of administration of estrogens is oral. Intramuscular injection is resorted to only when large doses have to be given, especially for carcinoma prostate.

1. Estradiol benzoate/cypionate/enanthate/valarate: 2.5–10 mg i.m.; OVOCYCLINP 5 mg inj, PROGYNON DEPOT 10 mg/ml inj.

2. Conjugated estrogens: 0.625–1.25 mg/day oral; PREMARIN 0.625 mg, 1.25 mg tab, 25 mg inj (for dysfunctional uterine bleeding).

3. Ethinylestradiol: for menopausal syndrome 0.02–0.2 mg/day oral; LYNORAL 0.01, 0.05, 1.0 mg tab, PROGYNONC 0.02 mg tab.

4. Mestranol: acts by getting converted to ethinylestradiol in the body: 0.1–0.2 mg/day oral; in OVULEN 0.1 mg tab, with ethynodiol diacetate 1 mg.

5. Estriol succinate: 4–8 mg/day initially, maintenance dose in menopause 1–2 mg/day oral: EVALON 1, 2 mg tab, 1 mg/g cream for vaginal application in atrophic vaginitis 1–3 times daily.

6. Fosfestrol tetrasodium: initially 600–1200 mg slow i.v. inj for 5 days, maintenance 120–240 mg/day oral or 300 mg 1–3 times a week i.v. HONVAN 120 mg tab, 60 mg/ml inj 5 ml amp.

7. Dienestrol: 0.01% topically in vagina: DIENESTROL 0.01% vaginal cream.

Transdermal Estradiol

A transdermal patch (EstradiolTTS) has become available in 3 sizes, viz. 5, 10 and 20 cm2 delivering 0.025 mg, 0.05 mg and 0.1 mg respectively in 24 hr for 3–4 days. The usual dose in menopause is 0.05 mg/day which produces plasma estradiol levels seen in premenopausal women in the early or mid follicular phase. Cyclic therapy (3 weeks on, 1 week off) with estradiolTTS is advised with an oral progestin added for the last 10–12 days. Beneficial effects of estradiolTTS on menopausal symptoms, bone density, vaginal epithelium and plasma Gn levels are comparable to those of oral therapy, but improvement is serum lipid profile is less marked.

Systemic side effects of estradiolTTS are the same as with oral estrogens, but are milder. Oral therapy delivers high dose of the hormone to the liver and increases synthesis of several proteins. EstradiolTTS avoids high hepatic delivery: consequently plasma levels of TBG, CBG, angiotensinogen and clotting factors are not elevated— risk of thromboembolic phenomena may not be increased.

ESTRADERMMX: Estradiol 25, 50 or 100 μg per 24 hr transdermal patches; apply to nonhairy skin below waist, replace every 3–4 days using a different site; add an oral progestin for last 10–12 days every month.

Recently a combined estradiol 50 μg + norethisterone acetate 0.25 mg patch has become available in some countries (ESTRAGESTTTS). Two weeks of estradermTTS followed by 2 weeks estragestTTS with patches changed twice weekly is used for total transdermal HRT.

A gel formulation of estradiol for application over skin is also available. OESTRAGEL 3 mg/5 g in 80 g tube; apply over the arms once daily for HRT.