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.
So, by drospirenone oral contraceptives I mean those that associate
the usual ethinyl estradiol with the new progestin drospirenone. 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.
to all the other existing synthetic progestins, drospirenone's progestogenic
effect is considered as being 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
analogue. About that, see Note
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.
containing drospirenone are also regarded as being 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
component ( ethinyl estradiol ).
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
The first drospirenone
oral contraceptive was released some years ago, consisting of 21 tablets,
each one of them containing 0.03mg of ethinyl estradiol and 3mg 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
0.03mg of ethinyl estradiol. ( Over the last 10 years, low-dose oral contraceptives
are those that contain 0.02mg of ethinyl estradiol .) So, this first "Pill"
containing drospirenone actually is "middle-dose."
But now finally
the first low-dose drospirenone "Pill" was released, 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 0.02mg of ethinyl estradiol
and 3mg of drospirenone and is to be taken with a 4-days 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 have more certainty 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.
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 the risk of causing heart arrhythmias ).
all of this, I must emphasize that the recently released low-dose drospirenone
oral contraceptive - containing 0.02mg of ethinyl estradiol and 3mg of
drospirenone in series of 24 tablets to be taken with a 4-days interval
between the series -, though possessing very, very interesting and important
features, is still too new for any adequate and correct evaluation of
its long-term effects in clinical practice. So, let us see what comes
Curiously, drospirenone, which is a progestin, was chemically
obtained by introducing some modifications on the anti-mineralocorticoid
spironolactone molecule. Here we must remark that, 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 to spironolactone,
it is an anti-mineralocorticoid 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 and hirsutism. 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 progesteronic effects, drospirenone also retained
the anti-mineralocorticoid and anti-androgenic effects of its chemical
Please note that this article was written in 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 ). In this way, it is too early for trying to arrive at any clinically
firm conclusion regarding its effects. Nevertheless, the perspective seems
to be optimistic.
For a better understanding of this article, see also my "Oral
Hormonal Contraceptives" published on this site in 2002.
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.