Drospirenone Oral Contraceptives
Dr. Nelson Soucasaux , Brazilian gynecologist
Some years ago a new progestin (synthetic progesterone) named drospirenone
was synthesized and, associated with the widely-known estrogen ethinyl estradiol,
is now giving rise to a new generation of oral contraceptives. When compared
to the other ones, these new contraceptives seem to possess some slightly
different metabolic effects due to drospirenone's particular properties.
Even so, their contraceptive mechanisms (the ways they prevent pregnancy)
are the same of all the other combined oral ones.
When compared to all the other existing synthetic progestins, drospirenone's
progestogenic effect is said to be closer to that of natural progesterone,
besides possessing a particular anti-mineralocorticoid and anti-androgenic
activity. Curiously, drospirenone was chemically obtained having the anti-mineralocorticoid
spironolactone as precursor (actually, drospirenone is considered a spironolactone
analog. About that, see Note below.)
The slight anti-mineralocorticoid activity and its consequent also slight
diuretic effect is due to the fact that, to some extent, drospirenone is
able to reduce the effect of aldosterone. (Aldosterone is the main adrenal
hormone responsible for controlling the retention of sodium and water in
the body and, therefore, the hydric balance.) Thus by slightly reducing
aldosterone's effect and stimulating natriuresis (the elimination of sodium
and water by the kidneys), the new "Pills" containing drospirenone
are said to be able to avoid or reduce the swelling frequently associated
with most of the other oral contraceptives.
"Pills" containing drospirenone are also said to be potentially
beneficial for women who exhibit the hydric retention and swelling typical
of many cases of premenstrual syndrome (though in clinical practice the
intensity of this effect may be still somewhat uncertain and, obviously,
will depend on each woman's reaction to the product). Natural progesterone
also possesses some diuretic effect.
As all the other progestins contained in the usual oral contraceptives
do not possess anti-mineralocorticoid effects, the sodium and water retention
sometimes induced by their estrogenic component is not counterbalanced.
Conversely, "Pills" containing drospirenone, due to the anti-mineralocorticoid
property of this new progestin, are said to be able to oppose this sodium
and water retention sometimes related to the oral contraceptives' estrogenic
Drospirenone is also endowed with a considerable anti-androgenic effect,
though it seems to be less than that of cyproterone (the widely-known anti-androgenic
progestin used in some oral contraceptives especially developed for women
with slight hypertrichosis , hirsutism and acne).
In this way, drospirenone "Pills" can also be indicated for slight
androgenic manifestations in women.
The first drospirenone oral contraceptive was released some years ago,
consisting of 21 tablets, each one of them containing 0.03 mg of ethinyl
estradiol and 3 mg of drospirenone and is to be administered as usual, with
a 7-days interval between each series of 21 tablets. Nevertheless, if we
look at it as a "Pill" released in the time of the "low-dose"
ones (regarding their estrogenic component), it cannot be considered as
such since each tablet still contains the 0.03 mg of ethinyl estradiol.
(Over the last 10 years, "low-dose" oral contraceptives are those
that contain 0.02 mg of ethinyl estradiol.) So, this first "Pill"
containing drospirenone actually is "middle-dose."
But now finally we have the first "low-dose" drospirenone
"Pill," and the manufacturers report a contraceptive efficacy
of 99%. Including an important change not only in the number of tablets
contained in each series but also in the interval between them, this new
oral contraceptive consists of 24 tablets, each one of them containing 0.02
mg of ethinyl estradiol and 3 mg of drospirenone and is to be taken with
a 4-day interval between the series. Thus, the number of tablets in each
series was increased and the interval between them was reduced. Though this
new product is being announced with a special emphasis as "the 'Pill'
for women with premenstrual syndrome," I think that more clinical experience
and time are needed so that we can be more about it (though theoretically
and pharmacologically it seems to be correct). We always must have in mind
that, even after their approval and release, all new medicines require a
long period of further careful observation.
Despite all of this, an aspect of drospirenone's pharmacology deserves
special attention: for antagonizing aldosterone's action, there is a potential
for a slight raise in the blood levels of potassium. Though this alteration
does not have any importance in normal women under normal conditions, special
care is required in patients who are taking a large number of very common
drugs that may raise the potassium levels (heightened potassium levels may
be dangerous for possibly causing heart arrhythmias).
Among these drugs are potassium-sparing diuretics, angiotensin-converting
enzyme inhibitors (ACE inhibitors), angiotensin-II receptor antagonists
and other aldosterone antagonists, including spironolactone itself (most
of these drugs are used for the treatment of hypertension and related conditions).
(As to the aforementioned relation between spironolactone and drospirenone,
see Note below.) In this way, the use of drospirenone
in women taking these medicines is not advisable or demands special care
and constant control of the potassium levels (there is even a warning from
the laboratory about that).
After saying all of this, I must emphasize that the recently released
"low-dose" drospirenone oral contraceptive - containing 0.02 mg
of ethinyl estradiol and 3 mg of drospirenone in series of 24 tablets to
be taken with a 4-day interval between the series -, though possessing very,
very interesting and important features, is still too new for any adequate
and correct evaluation of their long-term effects in clinical practice.
So, let's see what comes ahead.
drospirenone, which is a progestin, was chemically obtained by introducing
some modifications on the spironolactone molecule. As synthetic sexual steroids,
all previously existing progestins are also obtained having synthetic sexual
steroids as precursors. In this way, the novel progestin drospirenone is
a curious exception. As for spironolactone, it is a diuretic that functions
by antagonizing aldosterone's effect, consequently causing natriuresis (the
excretion of sodium and water by the kidneys). Besides, spironolactone is
also endowed with an anti-androgenic property and, for that reason, has
been also used for the treatment of hypertrichosis
Considering all of this we can see that drospirenone - as a synthetic
progesterone and, obviously, a sexual hormone -, very curiously was synthesized
just having an anti-mineralocorticoid as precursor. Besides having acquired
its remarkable and notorious progesteronic effects, drospirenone also retained
the anti-mineralocorticoid and anti-androgenic effects of its chemical precursor
P.S.1: Please note that this article was written between July and August
2007 - that is, only a few months after the release of the first "low-dose"
drospirenone oral contraceptive (though "middle-dose" drospirenone
"Pills" have been available in the market for approximately 4
years). It is way too early for trying to arrive at any clinically firm
conclusion regarding its effects. Nevertheless, its future seems to be optimistic.
P.S.2: See also my general article "Oral
hormonal contraceptives" published both here, on the MUM, and also
on my own site in 2002.
Copyright Nelson Soucasaux 2007
Nelson Soucasaux is a gynecologist dedicated to clinical, preventive
and psychosomatic gynecology. Graduated in 1974 by Faculdade de Medicina
da Universidade Federal do Rio de Janeiro, he is the author of several articles
published in medical journals and of the books "Novas Perspectivas
em Ginecologia" ("New Perspectives in Gynecology") and "Os
Órgãos Sexuais Femininos: Forma, Função, Símbolo
e Arquétipo" ("The Female Sexual Organs: Shape, Function,
Symbol and Archetype"), published by Imago Editora, Rio de Janeiro,
1990, 1993. He has been working in his private clinic since 1975.
Web site (Portuguese-English): www.nelsonginecologia.med.br