The Comparative Potencies of Birth Control and Menopausal Hormonal Drug Use

John Wilks
Reproduced with Permission

Recently it has been reported that women on hormone replacement therapy (HRT) had acquired a 26% increased risk of developing breast cancer.1 So dramatic was this finding it precipitated the early closure of the study. Worldwide media attention brought this and other findings onto the front page of major national newspapers. In Australia, the Therapeutic Goods Administration, charged with the regulation of all drugs prescribed in Australia, responded to this study by tightening the indications for HRT use.

As a result of this controversy over the safety of HRT, questions have arisen as to the safety of the birth control pill. Like HRT the birth control pill uses artificial hormones to alter the natural physiological characteristics of a woman's endocrine system, using pharmaceutically similar drugs. To help clarify this debate, the following citations and accompanying explanation will be, I trust, instructive.

"Historically, conjugated estrogens have been the most common agents for postmenopausal use, and 0.625mg/day is effective in most women (although 1.25mg is needed is some patients). In contrast most combined oral contraceptives in use employ 20 to 35mcg/day of ethinyl estradiol. Conjugated estrogens and ethinyl estradiol differ widely in their oral potencies: for example, a dose of 0.625mg of conjugated estrogens generally is considered equivalent to 5 to 10mcg of ethinyl estradiol.

It is important to recognize that the dose of estrogen used for postmenopausal hormone replacement therapy is substantially less than that used in oral contraception, taking into account the different potencies of the drugs normally employed in the two settings."2

A number of aspects of the above quote require clarification. First, conjugated estrogens are found in Premarin®, the brand at the centre of the current controversy. The hormone is obtained from the urine of pregnant horses. Ethinyl estradiol is the artificial estrogen commonly found in the birth control pill, and is manufactured in the laboratory.

Second, "mg" is an abbreviation for milligram, being one thousandth of a gram. Also, "mcg" is shorthand for microgram, being one millionth of a gram. Some texts use the Greek letter mu (which cannot be received properly by some e-mail browsers) with the letter "g" instead of "mcg" as an abbreviation for microgram, but they are synonymous terms.3

Hence, a dose of 0.625mg of conjugated estrogens is 0.625 thousands of a gram. This, according to Goodman and Gilman's text, is considered to be the bio-equivalent of 5-10 mcg of ethinyl estradiol. In pharmacology, bio-equivalence refers "to a drug that has the same effect on the body as another drug, usually one nearly identical in its chemical formulation."4

Modern forms of the birth control pill contain, on a cyclical basis, between 30 and 40 mcg (micrograms) of ethinyl estradiol.5 Hence, one birth control pill, at 40mcg, is at least four times stronger than the dose equivalent of 10mcg, which was previously indicated as begin equal to one Premarin 0.625mg tablet. Stated another way, the average dose of hormone in the birth control pill is, conservatively, four times stronger per dose than HRT. In the extreme (based upon the lowest strength comparison of ethinyl estradiol of 5mcg), the birth control pill is eight times stronger per tablet than a dose of HRT.

Similar, though slightly lower dose equivalent data is provided by Lange's Basic and Clinical Pharmacology. This text indicates that one birth control pill is the dose equivalent of 2-4 HRT tablets, depending on whether one calculates conservatively or extremely.6

Hence it is biologically and pharmacologically plausible to expect that the birth control pill would have at least the same rate of breast cancer in its users as than seen in HRT uses. According to the most recent research, this is exactly the case. Data presented at the third European Breast Cancer Conference reported that the risk of breast cancer was 26% higher in pill users compared to non-users.7 This finding is in harmony with more than 15 papers published since the mid-80s which have all indicated the birth control pill use in women, notably young women, causes an increase in the risk of developing breast cancer. To be consistent one would hope that the media will act to inform women of the dangers of the birth control pill also.


1 Women's Health Initiative. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA. 2002;288:321-333 [Back]

2 Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. McGraw-Hill 1996 p.1421 [Back]

3 Mosby's Medical, Nursing and Allied Health Dictionary. 5th ed (KN Anderson, editor) 1998 [Back]

4 Mosby's, ibid, p.193 [Back]

5 MIMS Product Information 2002 Triphasil 28 (Tablets) Levonorgestrel 50 mcg, ethinyloestradiol 30 mcg (6 brown s-c tabs); levonorgestrel 75 mcg, ethinyloestadiol 40 mcg (5 white s-c tabs); levonorgestrel 125 mcg, ethinyloestradiol 30 mcg (10 yellow s-c tabs); inactive (7 red s-c tabs); gluten free [Back]

6 Lange's Basic and Clinical Pharmacology. (8th ed) McGraw-Hill 2001. B G Katzung (Editor) [Back]

7 Birth control pill found to raise breast cancer risk,   [Back]