Transcript HORMONSKA KONTRACEPCIJA SA 17

Endrocrinologist Gregory
Pincus (1903-1967) is best
known for developing the
oral contraceptive, or birth
control pill.
THE FIRST OC:
In 1960 the compound was approved
by the U.S. Food and Drug Administration
as the first contraceptive pill.
The pill was manufactured by G. D.Searle
Company under the name Enovid.
Enovid was sold only by prescription.
Real Contraceptive Choices:
Alternatives to Risky Hormone Pills,
Patches and Shots
July 10, 2010
The birth control pill was first introduced to the
American public for contraceptive use in 1960. By 2002,
11.6 million US women were on “the Pill” according to
CDC statistics[1], making it the nation’s leading method
of contraception.
Eighty percent of American women have used oral
contraceptives at some point in their lives, according to
a paper in the Journal of the American College of
Cardiology[2
What side effects could I have whilst taking OC?
The vast majority of patients taking OC feel very well but, as with any medicine
that has benefits, some minor side effects are occasionally reported. These include:
* altered body weight (some gain a few pounds and others lose a little).
* nausea and vomiting.
* mastalgia (breast tenderness).
* headaches (OC should be stopped if they become severe).
* altered libido (sex drive - Q15.5) with many women noticing an increase and others a reduction.
* depression.
* reduced or absent menstrual flow.
These side effects usually settle within two or three months.
About the pill:
In 1960, after more than a decade of research, the
United States Food and Drug Administration [USFDA]
approved the first oral contraceptive pill, which
contained high doses of hormones oestrogen [150 µg]
and progestin [9.85 mg].
These pills satisfied women's need for convenient,
safe and reliable contraception.
However, some users experienced side effects such
as headache, nausea, cramps and weight gain.
Though these side effects were temporary, they
led to more research and lowering of the hormonal
doses in the pills.
Today's pills contain around 20-35 mg of estrogen.
This has significantly reduced the side-effects also.
Pill use and smoking:
Women who smoke have a
higher risk of stroke than
non-smokers.
Particularly for older women,
the combination of oral
pills and smoking can increase
their risk of stroke and
blood clots.
Benefits of the pill
Apart from preventing pregnancy, the pills also have
other health benefits like:
-
Regular menstruation
Less severe premenstrual syndrome, dysmenorrhoea
Lowered risk of anaemia [due to lighter menstrual flow]
Protection against some cancers like endometrial and
epithelial cancer
- Prevention of ectopic pregnancy
•
•
•
•
1st pill : 150 mcg EE + 9.85 P
POP – in the 1970s
Gradually diminishing EE dose
Switching from EE to natural E
(E2V and finally 17-beta-E2)
The combined oral contraceptive pill
has been used by an estimated 300
million women worldwide since it was
first developed.
In recent years it has been linked with both
an increased risk of some forms of cancer and
as having a protective effect against some
other cancers – leading to considerable
confusion for women.
Beside that, it has been proven that syntethic
E has considerable number of risks as compared
to the natural estrogen.
Undesirable side-effects
of the classical OCs
Table 8A
The Four Large Studies That Measured Early OCP Use and the Risk of Breast
Cancer to Women Under the Age of 45
Author
Year
Size of Study
Findings
Wingo (17)
CASH Study
12/80-82
2089 less than age
45
40% increased risk
ages 20-44
Rosenberg25*
1977-1992
1427 less than age
45
88% increased
risk**
1983-1990
747 less than age
45
50% increased risk:
for use within 5
years of
menarche
(parous women)
5/90-12/92
1648 less than age
45
42% increased risk
(parous
women)**
White26
Brinton (19)
* This study did not control for abortion. >
** Calculated from raw data found in their paperÑsee end of chapter for details.
Oral Contraceptives Reduce Long-Term Risk of Ovarian Cancer
Since they were first licensed nearly 50 years ago, birth control pills containing estrogen
have prevented some 200,000 cases of ovarian cancer world-wide, estimate the authors
of a study published January 26, 2008, in The Lancet.
Further, in the absence of having taken oral contraceptives, half of these women would
have died of the disease.
NCI Cancer Bulletin, vol. 5/no. 3, Feb. 5, 2008
Oral Contraceptives Cut Ovarian Cancer Risk
The Pill prevents as many as 30,000 deaths each year, study says
By Steven Reinberg
Posted 1/25/08
U.S. National Cancer Institute.
Relation between oral contraceptive hormones and blood clotting
Oral contraception with conventional oestrogen/progestogen preparations
produces raised levels of clotting factors and increased platelet aggregation.
Although these changes do not involve as broad a spectrum of clotting
factors as thrombosis and the third trimester of pregnancy, they do not
appear a desirable side effect and may be responsible for the increased
risk of thrombosis. Oral contraception with progestogen alone does not
appear to cause similar clotting and platelet changes.
L.Poller , J Clin Pathol Suppl (Assoc Clin Pathol). 1969; 3: 67–74.
Blood Coagulation & Fibrinolysis:
July 2002 - Volume 13 - Issue 5 - pp 373-381
Effect of second- and third-generation oral contraceptives on
fibrinolysis in the absence or presence of the factor V Leiden mutation
Kemmeren, J. M.; Algra, A.; Meijers, J. C. M.; Bouma, B. N.; Grobbee, D. E.
Third-generation oral contraceptives (OC) have been associated with an increased risk
of venous thrombosis compared with second-generation OC. To find an explanation for
this increased risk, the effect of a second- and third-generation OC and of the
progestagens used in these pills on several fibrinolytic parameters was studied in the
absence or presence of the factor V Leiden mutation.
In conclusion, the effect of oral contraceptives on fibrinolytic parameters is
largely independent of the type of progestagen. The increased fibrinolytic
activity during OC use appears to be induced by the estrogen component.
Birth Control Pills & Blood Pressure
Progesterone Can Increase Blood Pressure
Progesterone is a hormone that can affect blood pressure. The
mechanism by which this occurs is complicated, but involves both
hormone cascades and direct effect on small blood vessels. Because of
these effects, it is possible that taking birth control pills can cause your
blood pressure to rise. This increase in blood pressure can range from
very mild to potentially serious, and may sometimes warrant
discontinuing the birth control.
Oral contraceptives and blood pressure
I. R. Fisch and J. Frank , Vol. 237 No. 23, June 6, 1977
Both cross-sectional and longitudinal analysis of data from 13,358 women
showed that oral contraceptive use is associated with a slight but statistically
significant (P lesser than .05) rise in mean blood pressure, which is reversible.
The age-adjusted proportion of oral contraceptive users with a blood pressure
over 140/90 mm Hg was about three times that on nonusers.
Sex hormones and hypertension
Raghvendra K. Dubeya,b,*, Suzanne Oparile, Bruno Imthurnb
and Edwin K. Jacksona,c,d , Cardiovascular Research 2002 53(3):688-708
Estradiol levels increase 50–180-fold during pregnancy, and these
increases are associated with substantial reductions in blood pressure
If endogenous estradiol does lower blood pressure, administration of
estrogenic preparations to women might also be expected to reduce
blood pressure. However, data on the effects of estrogenic preparations
on blood pressure are inconsistent, and include reports of blood pressure
lowering, blood pressure elevating, and blood pressure
neutral effects.
Administration of estradiol (oral or transdermal patches) to normotensive
postmenopausal women either reduced or had no effect on blood pressure
Contraceptive estrogenic preparations tend to increase blood pressure;
conjugated equine estrogens appear to have little effect on blood pressure,
and estradiol tends to lower blood pressure
Kletzky O.A., Marrs R.P., Howard W.F., McCormock W., Mishell D.R. Jr. Prolactin synthesis and release during pregnancy and puerperium. Am J Obstet Gynecol. (1980)
136:545–550.
Elias A.N., Meshkinpour H., Valenta L.J. Attenuation of hypertension by conjugated estrogens. Nephron (1992) 30:89–92.
WHO Task Force on Oral Contraceptives. The WHO Multicentre Trial of the Vasopressor Effects of Combined Oral Contraceptives. I. Comparisons with IUD.
Contraception 1998;40:129–145.
Ethinyl estradiol acutely attenuates abnormal coronary vasomotor
responses to acetylcholine in postmenopausal women
SE Reis, ST Gloth, RS Blumenthal, JR Resar, HA Zacur, G Gerstenblith
and JA Brinker
Department of Medicine, Johns Hopkins University, Baltimore, Md.
EE attenuates abnormal coronary vasomotor responses to acetylcholine in
postmenopausal women. EE also decreases basal coronary vasomotor tone
as manifested by increased coronary flow, decreased resistance, and
increased epicardial cross-sectional area. These acute effects of estrogen
on coronary vasoreactivity may explain, in part, the cardioprotective effects
of estrogen in postmenopausal women.
Circulation, Vol 89, 52-60, Copyright © 1994 by American Heart Association
Effects of estrogens and selective estrogen receptor modulators
on vascular reactivity in the perfused mesenteric vascular bed
Connie J. Mark, Rabelais Tatchum-Talom, Douglas S. Martin,
and Kathleen M. Eyster
Ethinyl estradiol increased vasoconstriction in response to KCl and 5-HT,
whereas responses to estradiol benzoate and RAL were less consistent.
Am J Physiol Regul Integr Comp Physiol 293: R1969-R1975, 2007. First published September 19, 2007
The American Journal of Medicine
Volume 49, Issue 5 , Pages 630-648, November
1970
M.D. Herman Adlercreutz, M.D. Raimo Tenhunen
This article deals with some aspects of the interaction between natural and
synthetic female sex hormones and the liver. Because of the close structural
relationship between some progestogens and anabolic steroids the effect of the
latter compounds on the liver is also reviewed. The following effects of anabolic
steroids, progesterone, synthetic progestogens, estrogens, compounds with
estrogenic activity and oral contraceptives on liver are discussed in greater detail:
Effect on morphology including light and electron microscopic changes; effect on
bile secretion, with special emphasis on cholestatic effects; effect on biochemistry of
the liver cell with special regard to enzyme induction, the drug-metabolizing enzyme
system of the liver cell, porphyrin metabolism and changes in mitochondrial
enzymes. Jaundice and porphyria due to steroids are also discussed, and the close
connection between recurrent (intrahepatic cholestatic) jaundice of pregnancy and
jaundice due to oral contraceptives is emphasized. The metabolism of female sex
hormones in liver disease is briefly reviewed. In the general discussion the main
topics are: Effect of oral contraceptives on the liver, the mechanism of the
cholestatic effect of steroids, possible genetical defects involved and the likely
connection between the metabolism of hormonal steroids and the formation of
gallstones in women.
State-of-the-art paper | January 2009
Contraceptive Hormone Use and Cardiovascular
Disease FREE
Chrisandra L. Shufelt, MD, MS; C. Noel Bairey Merz, MD,
FACC doi:10.1016/j.jacc.2008.09.042
J Am Coll Cardiol. 2009;53(3):221-231.
In the U.S., hormone therapy delivered as oral contraceptives (OCs) is one of the most commonly prescribed birth
control methods, used by 11.6 million or 19% of women (1). Since their introduction in the 1960s, OCs have been
used by approximately 80% of U.S. women at some point in their life to block ovulation, implantation, and,
therefore, pregnancy (2). The simplicity of the available regimens, low frequency of side effects, and relative safety
compared with pregnancy (3) has resulted in widespread use.
Observational studies demonstrate that young women have a relatively lower age-adjusted risk of cardiovascular
disease compared with men. Cardiovascular risk rises after menopause (4), suggesting that endogenous
reproductive hormones may play a protective role. We and others have further demonstrated that disruption of
ovulatory cycling, indicated by estrogen deficiency and hypothalamic dysfunction (5), or irregular menstrual cycling
(6-7) in pre-menopausal women is associated with an increased risk of coronary atherosclerosis and adverse
cardiovascular events, respectively. The concept that pre-menopausal contraceptive hormone use may be
protective for atherosclerosis is appealing.
Conversely, recently published data on mortality from cardiovascular disease has shown that since the year 2000,
mortality rates have increased in women between the ages of 35 and 44 years compared with decreases in all
other age groups (4). Increased rates of obesity and smoking and declines in physical activity are prevalent in this
group of midlife women (8). Also coincident in this age group was an increased OC use during the same decades,
from 4% to 17% (1-2). In part because OCs are effective and safe for contraception, and because pre-menopausal
women are at relatively lower cardiovascular risk than the general public, there has been relatively little specific
study devoted to evaluating links between contraceptive hormone use and cardiovascular disease.
State-of-the-art paper | January 2009
Contraceptive Hormone Use and Cardiovascular
Disease FREE
Chrisandra L. Shufelt, MD, MS; C. Noel Bairey Merz,
MD, FACC
J Am Coll Cardiol. 2009;53(3):221-231.
doi:10.1016/j.jacc.2008.09.042
* Mechanisms of Estrogen and Progestin Action on the Cardiovascular System
* Lipoproteins
* Blood pressure
* Glucose tolerance (DM)
* Thrombosis
* Coronary vasomotion
* Arrhytmogenesis
1: Acta Obstet Gynecol Scand. 1981;60(2):203-6.
Effectivity and acceptability of oral contraceptives containing natural
and artificial estrogens in combination with a gestagen.
A controlled double-blind investigation.
Serup J, Bostofte E, Larsen S, Westergaard J.
With the purpose of investigating effectivity and acceptability of an oral contraceptive containing micronized natural estrogens (estradiol-17 beta 4 mg + estriol 2
mg/norethisterone acetate 3 mg per tablet) versus a contraceptive containing artificial estrogen (ethinyl estradiol 50 micrograms/ norethisterone acetate 3 mg
per tablet), a controlled double-blind investigation was performed in 111 young women. The investigation was designed for 12 cycles. The tablets were given
consecutively for 3 weeks with 1 week's interruption. In the natural estrogen group 57 women completed 504 cycles, in the artificial estrogen group 54 women
completed 510 cycles (Table 1). No pregnancies occurred. There were highly significantly more terminations due to bleeding irregularities (p less than 0.001),
and highly significantly more spotting (p less than 0.001), breakthrough (p less than 0.001) and amenorrhea (p less than 0.001) episodes in the natural estrogen
group (Tables II and III). Bleeding irregularities on natural estrogens did not subside during the trial (Table IV). There were a few more psychiatric and CNS
symptoms on natural estrogen (p less than 0.05), but other side effects did not differ between the two preparations (Table V). Blood pressure and weight did not
vary significantly. Despite documented metabolic advantages, the natural estrogen tablet investigated was not found to be clinically acceptable for general
usage because of the high incidence of bleeding irregularities. It is conceivable that a change of the estrogen/gestagen ratio, using a variable 3-week schedule,
would reduce the number of bleeding irregularities.
PIP: With the purpose of investigating effectivity and acceptability of an oral contraceptive containing micronized natural estrogens (estradiol-17beta 4 mg +
estriol 2 mg/norethisterone acetate 3 mg/tablet) versus a contraceptive containing artificial estrogen (ethinyl estradiol 50 mcg/norethisterone acetate 3mg/tablet),
a controlled double-blind investigation was performed in 111 young women. The investigation was designed for 12 cycles. The tablets were given consecutively
for 3 weeks with 1 week's interruption. In the natural estrogen group, 57 women completed 504 cycles; in the artificial estrogen group 54 women completed 510
cycles. No pregnancies occurred. There were highly significantly more terminations due to bleeding irregularities (P 0.001), and highly significantly more spotting
(p 0.001), breakthrough (p 0.001) and amenorrhea (p 0.001) episodes in the natural estrogen group. Bleeding irregularities on natural estrogens did not subside
during the trial. There were a few more psychiatric and central nervous system symptoms on natural estrogen (p 0.05), but other side effects did not differ
between the 2 preparations. Blood pressure and weight did not vary significantly. Despite documented metabolic advantages, the natural estrogen tablet
investigated was not found to be clinically acceptable for general usage because of the high incidence of bleeding irregularities. It is conceivable that
a change of the estrogen/gestagen ratio, using a variable 3-week schedule, would reduce the number of bleeding irregularities.
PMID: 7018165 [PubMed - indexed for MEDLINE]
Vaginal bleeding patterns among
women using one natural and eight
hormonal methods of contraception
E.M. Belsey
Contraception
Volume 38, Issue 2 , Pages 181-206, August 1988
Menstrual diary records were obtained from a total of 5257 women using nine different methods of contraception,
one natural and eight hormonal. This paper presents a comparative analysis of their vaginal bleeding patterns.
The analytic procedures follow the recommendations of a recent WHO workshop on bleeding pattern analysis,
which involve dividing each subject's diary into successive 90-day reference periods, calculating ten indices for
each period, and classifying women according to whether they have “clinically important” bleeding disturbances.
In general, the findings of this analysis confirm those of previous studies. Women using the natural method, who
were deliberately selected for the regularity of their menstrual cycles, averaged three bleeding/spotting episodes
of length 5 days in each 90-day period, with very little variability within or between women. Subjects given a
combined oral contraceptive had more regular patterns than any other treated group, with short (4-day) episodes
and 23–24 day bleeding-free intervals. Progestogen-only pill users had more frequent, longer episodes and
shorter, less predictable intervals than combined pill users. Contrary to widely-held beliefs, the progestogen-only
pills produced fewer spotting days than the combined pills, and almost no spotting episodes at all. Nearly half of
vaginal ring users experienced some menstrual disturbance in each period; their most common problems were
irregular, infrequent or prolonged bleeding. Women using the long-acting injectable, depot medroxyprogesterone
acetate, had totally unpredictable patterns, with infrequent but prolonged bleeding/spotting episodes. The
incidence of amenorrhea rose from just under 10% in their first injection interval to over 40% in their fourth.
The methods of analysis recommended by WHO in 1985 still require substantial refinement. Nevertheless, they
are more sensitive than those used previously for WHO trials and produce an easily understood, clinically
meaningful characterization of bleeding patterns.
Maturitas
Volume 21, Issue 1, January 1995, Pages
27–32
•E. Hirvonen , a,
•H. Allonenb,
•M. Anttilac,
•Y. Kulmalab,
•T. Rantad,
•H. Rautiainene,
•P. Sipiläf,
•P. Ylöstalog, h
An open multicenter trial was performed in six centers in Finland to study the efficacy, safety and
acceptability of a new biphasic oral contraceptive pill containing natural estradiol and cyproterone
acetate. The participants were 288 women with a mean age of 39.3 ± 3.4 years (range 30–49)
who were willing to use the new pill as their only contraceptive method. In total, 23% of the
women were smokers. The cumulative experience was 2800 treatment cycles during the first
year. The net 12-month continuation rate was 63%. One pregnancy occurred in a woman who
lost 5 tablets in the second treatment cycle, which gives a 12-month cumulative pregnancy rate
of 0.4%. Serum progesterone values, determined twice during the third treatment cycle, showed
ovulation inhibition in 95% of women. There were no serious side effects. Intermenstrual
bleeding was recorded by 35.5% and 24.5% of women at 3 and 12 months, respectively. The
bleedings became scantier in most women and dysmenorrhoea disappeared. No changes were
observed in total and high density lipoprotein cholesterol concentrations after 1 year. With the
exception of intermenstrual spotting, the efficacy, safety and acceptability of the new pill was
almost as good as that of the modern low dose oral contraceptives. This is the first pill containing
natural estradiol that has gained clinical acceptance and which can also be prescribed for
smokers over 35 years old until the climacteric.
Experimental and Toxicologic Pathology
Volume 50, Issues 4–6, September 1998,
Pages 458–464
Approaches to the replacement of
ethinylestradiol by natural 17β-estradiol
in combined oral contraceptives
Dedicated to Prof. Dr. Wolfgang Klinger on
occasion of his 65th birthday on July 3,
1998.
•H. Hoffmann1, ,
•C. Moore1,
•H. Zimmermann1,
•W. Elger2,
•S. Schwarz1,
•T. Gräser1,
•M. Oettel1
The strong hepatic estrogenic actions of ethinylestradiol (EE)
are very likely to be the cause of the cardiovascular morbidity
related to the use of combined oral contraceptives (COCs). This
survey presents results of EE replacement inCOCs with natural
17β-estradiol (E2) in the following stages: reduction of EE to
daily doses of 0.01 mg and concomitant replacement with E2
(as valerate, EV), complete replacement of EE with E2 using a
novel multiphasic combination containing EV and the progestin
dienogest (DNG), and the use of natural E2 to develop estrogen
sulfamates (J 995) showing sufficient dissociation of uterine
from liver estrogenicity. Recent data from preclinical and clinical
studies show that these approaches seem to be promising.
06/17/2009 Bioidentical birth control
"Bayer Schering Pharma, the pharmaceutical giant that makes the YAZ
contraceptive pill, claims that they have developed the first ‘natural’ birth control pill
in the world. They have already launched the pill, Qlaira, in the UK after doing tests
with it on 3,000 women.
Instead of using synthetic hormones, like those that are found in other
contraceptive pills, Qlaira uses bioidentical oestrogen hormones from natural
plants, which is identical to the estrogen in the body. "
There's a bit more if you follow the link, including this sequence of sentences:
"Although bioidentical hormones are boasted as safer than synthetic hormones,
there is some scientific evidence that supports the theory. In January, Suzanne
Somers appeared on The Oprah Winfrey show, crediting bioidentical hormones
with helping her get through menopause." I thought that was pretty hilarious.
Anyway, this will be an interesting development to keep an eye on. I wonder if there
is potential for less side effects, since the hormones are identical to those
in our own bodies.
Read more at VaginaPagina:
http://vaginapagina.livejournal.com/16388054.html#ixzz2az7ju8x3
Estradiol Valerate + dienogest (QLAIRA)
•
•
•
•
•
D1-D2
D3-D7
D8-D24
D25-D26
D27-D28
E2V 3mg
E2V 2mg + DNG 2mg
E2V 2mg + DNG 3mg
E2V 1mg
placebo
1
I
14
II
ESTRADIOL
VALERATE
DIENOGEST
III
26 28
IV
(V)
PLACEBO
17-β-Estradiol + nomegestrol acetate (ZOELY)
• monophasic
• E2 1.5 mg + NomAc 2.5 mg
• 24+4 regimen
1
ESTRADIOL
NOMAC
14
24
PLACEBO
28
Duration (days) of bleeding in the RVS
(Intent-To-Treat Population)
REGIMEN
Number of women
Total duration
Intercurrent bleeding
Withdrawal bleeding
cycle 0
cycle 1
cycle 2
21 DAYS
24 DAYS
36
39
15.5  0.93 12.4  0.78
p
< 0.05
2.4  0.74
1.3  0.48
0.22
4.1  0.30
5.0  0.44
4.8  0.31
4.6  0.51
3.5  0.22
3.9  0.27
0.38
< 0.05
< 0.01
Mean change in SHBG after 3 cycles of
treatment with E2/NOMAC (24-day
regimen)
MEAN
SD
RANGE
Control cycle
(nmol/L)
75.1
33.39
22 ;155
Treatment cycle
(nmol/L)
94.1
39.43
29 ; 177
Change (%)
33.3
38.71
-24 ; 130
Mean change (%) in SHBG:comparison
with different monophasic
contraceptives
300
200
100
0
E2/NOMAC
ALESSE
ORTHOTRICYCLEN
MIRETTE
YASMIN
NUVARING
EVORA
Mean change (%) in SHBG:comparison
with different monophasic
contraceptives
300
200
100
0
E2/NOMAC
ALESSE
ORTHOTRICYCLEN
MIRETTE
YASMIN
NUVARING
EVORA
Nestorone
Trimeges
NOMAC
Drospir
NETA
NEWER P MOLECULES
• DSP = antimineralocorticoid
• DNG = antiandrogenic
• NES = highly progestational (nonoral)
• NOM Ac = highly
antigonadotropic
• TMG = highly progestational
• None is androgenic nor estrogenic
GREAT NUMBER OF ADVANTAGES
EXIST WHEN IN ORAL CONTRACEPTION
EE
IS REPLACED WITH
NATURAL ESTROGEN!
(we have been waiting for it almost 50 years!)
CONCLUSIONS:
CONTRACEPTION WITH NATURAL
HORMONES MAY HAVE LESS SIDE EFFECTS
CONCLUSIONS:
CONTRACEPTION WITH NATURAL
HORMONES MAY HAVE LESS SIDE EFFECTS
CONTRACEPTIVE EFFECT DEPENDS MORE
ON PROGESTIN (IMPORTANCE OF CHOOSING
THE MOST METABOLIC-FRIENDLY ONE!)
CONCLUSIONS:
CONTRACEPTION WITH NATURAL
HORMONES MAY HAVE LESS SIDE EFFECTS
CONTRACEPTIVE EFFECT DEPENDS MORE
ON PROGESTIN (IMPORTANCE OF CHOOSING
THE MOST METABOLIC-FRIENDLY ONE!)
TODAY - E2
TOMORROW MAYBE E4
CONCLUSIONS:
CONTRACEPTION WITH NATURAL
HORMONES MAY HAVE LESS SIDE EFFECTS
CONTRACEPTIVE EFFECT DEPENDS MORE
ON PROGESTIN (IMPORTANCE OF CHOOSING
THE MOST METABOLIC-FRIENDLY ONE!)
TODAY - E2
TOMORROW MAYBE E4
FUTURE IMPROVEMENTS – TRANSDERMAL
ADMINISTRATION (GEL)
Over 50 years of oral contraception …
…today, first users are grandmothers!