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Risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel: nested case-control study based on UK General Practice Research Database

BMJ 2011; 342 doi: (Published 21 April 2011) Cite this as: BMJ 2011;342:d2139

Rapid Response:

Oral Contraceptives containing acne-treating oestrogenic drospirenone cause more thrombosis than those with acne-causing androgenic levonorgestrel.

The confirmation from Lianne Parkin and colleagues that combined oral
contraceptives (COCs) containing drospirenone cause more thrombosis than
those containing levonorgestrel should be a cause for concern among those
promoting hormonal contraceptive use.1

In 1969 my then anonymous BMJ Editorial "Changing Oral
Contraceptives" summarised the problems caused by changing doses and
hormone balances of a large range of combined oral contraceptives.2 Higher
doses or balances of oestrogen caused more venous effects including
thrombosis while strongly progestogenic combinations caused more
arteriolar changes in endometrial blood vessels with more arterial side
effects like migraine and hypertension and also more depressive mood
changes due to increases in monoamine oxidase activities. Weaker
combinations caused more unplanned pregnancies and irregular bleeding.

It is interesting that Thomson and colleagues have confirmed my 1969
findings of microvascular vasodilation with the available COCs which cause
the most thrombosis.

In 2011 it is COCs containing 150ug desogestrel and 3mg drospirenone
which significantly increased endothelium-dependent vasodilation in both
large vessels and peripheral microvasculature.3

In 1969 I discovered that it was the progestogens with inherent
oestrogenic activity, norethisterone acetate and ethynodiol diacetate,
which caused most dilated venous sinusoids in women with vein complaints
and thrombosis, especially when combined with higher doses of

Oestrogenic progestogens, like drospirenone, are used to treat acne
but COCs with a higher dose or balance of estrogen cause more thrombosis.
Androgenic progestogens like levonorgestrel which has quite powerful
androgenic activity but no oestrogenic activity may cause or exacerbate

Powerful progestogens also cause more breast cancer than oestrogens.
In the past year alone there has been an explosive increase in research
into why progesterone use causes breast cancer. Surely a more serious
promotion of non-hormonal methods of contraception is long overdue as
world overpopulation becomes ever more problematic.

1 Parkin L, Sharples K, Hernandez RK , Jick SS. Risk of venous
thromboembolism in users of oral contraceptives containing drospirenone or
levonorgestrel: nested case-control study based on UK General Practice
Research Database. BMJ 2011; 342:d2139.

2 Anon Editorial. Hormone balance of oral contraceptives. BMJ

3 Thompson AK, Przemska A, Vasiloupou D, Newens KJ, Williams CM.
Combined oral contraceptive pills containing desogestrel or drospirenone
enhance large vessel and microvasculature vasodilation in healthy
premenopausal women. Microcirculation. 2011 Mar 7. doi: 10.1111/j.1549-

4 Grant ECG. Venous effects of oral contraceptives. BMJ 1969;4:73-

5 Dickey RP. Managing contraceptive pill patients. Essential
Medical Information Systems,Inc. 1994 Eighth Edition.

Competing interests: No competing interests

24 April 2011
Ellen CG Grant
physician & medical gynaecologist
Kingston-upon-Thames, KT2 7JU