BRIEF CLINICAL UPDATE


New Developments in Contraception


Camelia A. Davtyan, M. D.

Contraceptive use in the Unites States has been increasing over the years,
with 39 million users in 1995 (64%), compared to 1982, when 30 million (56%)
childbearing age women were using birth control. 1 Despite this trend, the
rate of unwanted preg-nancy is still one of the highest in the industrialized
world with almost half of all pregnancies unintended. 2

One of the major causes
of this phenomenon is the fact that many women do not use contraception correctly
and consistently. Oral contraceptives are the most commonly used reversible
contraceptives. 1 In a given cycle, 50% of pill-takers miss one pill and
22% miss more than 2 pills. 3 Over the recent years, longer acting hormonal
contraceptives have become avail-able, with similar efficacy and side effect
profiles with oral hormonal contraception. Also, new formula-tions of oral
contraceptives have been developed, in the attempt to minimize side effects.
A new, longer acting hormonal IUD was approved by the FDA as has been a non-surgical
sterilization method. There has been progress in natural family planning with
new electronic fertility monitors.

New Developments in Sterilization:

Essure was approved by the
FDA in 2002 and consists of two soft metallic coils introduced hysteroscopically
in the proximal aspect of the fallopian tubes through a transcervical tubal
access catheter. Subsequently, there is a local inflammatory and fibrotic response
which leads to tubal occlusion within 3 months. Alternate contraception should
be used for 3 months after the procedure. A hysterosalpingogram performed 3
months after the procedure should confirm the tubal occlusion and proper location
of the coils. FDA approval was based on the results of two
clinical trials involving 676 women who were followed for 1-2 years after
the Essure insertion procedure and no pregnancies were detected. 4 It is expected
that about 10% of women will not be able to have the coils inserted due to
abnormal tubal anatomy. Patients are expected to go home about 45 minutes after
the procedure and return to work/ regular physical activities within 1-2 days.

New Developments in Oral Contraception :

Yasmin is a new combination
oral contraceptive with 30 mcg of ethynil estradiol and a new progestin, drospirenone,
which has antiandrogenic and antimin-eralocorticoid effects similar to endogenous
proges-terone. 5,6 This progestin attenuates the estrogen-induced stimulation
of the renin-angiotensin-aldos-terone system and blocks testosterone binding
to androgen receptors, thus having the potential to decrease blood pressure
and LDL cholesterol and increase HDL cholesterol. 6 It also has a slight diuretic
effect which counteracts the estrogen induced fluid retention. 7,8 Given this
diuretic effect and antiminer-alocorticoid activity, the manufacturer states
that this contraceptive should not be used in women with hepatic, renal or
adrenal disease and in women taking potassium sparing diuretics or any medications
that can increase potassium levels.

A multitude of oral low dose estrogen formula-tions
are now available (Alesse, Lo-Estrin 1/ 20, etc) containing 20 mcg ethynil
estradiol, which are associ-ated with less estrogen related side effects
at the expense of more intermenstrual spotting and bleeding.

Cyclessa, an oral
contraceptive with 25 mcg ethynilestradiol, offers better cycle control
than the 20 mcg estrogen contraceptives and still maintains a low incidence
of estrogen related side effects. 9

There seems to be similar efficacy and
side effect profile when active pills are used continuously for 3 months and
placebo pills are used for a week every three months to allow for withdrawal
bleeding. Many patients believe that stopping menses altogether is not \"natural\" so clinicians should counsel them that the monthly withdrawal bleeding
while taking the placebo pills in the contraceptive pack is also not \"natural\".
In women with menstrual related symptoms (anemia, endometriosis, migraines, premenstrual
syndrome, severe dysmenorrhea, menorrhagia, seizure disorder) this option can
be particularly useful. 10

Mircette, a shorter pill-free interval formulation,
has 20 mcg ethynil estradiol for 21 days, two days of placebo and 5 days of
10 mcg ethynilestradiol. It seems to offer benefits to women with estrogen
with-drawal headaches or other symptoms related to estrogen withdrawal.

New Developments
in Long-Acting Hormonal Contraception:

Lunelle is an injectable combination
of 5 mg estradiol cypionate and 25 mg medroxyprogesterone acetate which is
administered monthly (27-33 days) by intra-muscular injection into the arm,
thigh or buttocks and suppresses ovulation for up to 42 days. 11,12 It has
a similar efficacy and side effect profile with the oral contraceptives and
offers a possible compliance advantage given the once a month dosage. The
bleeding profile is same or better than oral contracep-tives. There seems
to be an excess weight gain of 2-8 lbs in Lunelle users compared to oral
contraceptives, which might be problematic in clinical use. 11

OrthoEvra
is a contraceptive patch that releases 20 mcg ethynilestradiol and 150
norelgestromine (active metabolite of norgestimate) daily. It is applied on
abdomen, buttocks, upper outer arm on torso weekly for 3 weeks a month starting
the first day of menses. Withdrawal bleeding happens during the fourth week
when the patch is not used. The patch is relatively large (2 in by 2 in) compared
to the smaller patches used for menopausal hormone replacement.

Humidity, heat and exercise do not alter the pharma-cokinetics of the patch.
13 A small percentage of patches detach (1.8%) or partially detach (2.9%) requiring
replacement. 14 Heavier women (> 198 lbs or 90 kg) experience more method
failure and should be advised to use an alternate contraceptive. 15 The efficacy
and side effect profiles are similar to oral contraceptives, with the exception
of more transient breakthrough bleeding and mastalgia during the first few
cycles on the patch. 15

Nuvaring is a flexible silicone ring with a diameter
of 2.1 inches which releases 15 mcg of ethynilestradiol and 120 mcg etonogestrel
(active metabolite of desogestrel) daily. It is placed in the upper vagina
within 5 days of the onset of menses, then worn for 3 weeks and removed the
fourth week to allow for withdrawal bleeding. If removed for intercourse,
it should be reinserted within 3 hours. The efficacy and side effect profiles
are similar to oral contraceptives with the addition of possible local irri-tation
and vaginitis. 16 Unlike the diaphragm, it does not require sizing or fitting.

New Developments in Emergency Contraception:

There are two emergency
contraception kits available by prescription which need to be used within 48-72
hours after unprotected intercourse. Preven is a combination of 0.05 mg ethynil
estradiol and 0.25 levonorgestrel administered in two doses of two tablets
each, twelve hours apart. Plan B is a progestin only formulation of 0.75 mg
levonorgestrel adminis-tered as one tablet followed by a second dose after
12 hours. It has a slightly higher efficacy than Preven and a better side effect
profile and can be administered in women who have contraindications to estrogen.
17

New Developments in Intrauterine Contraception:

Mirena is a
hormonal IUD which releases 46 mg levonorgestrel over 5 years. Women experience
heavier bleeding in the 1-2 cycles after insertion, but in time, they develop
oligo-amenorrhea with a 97% reduction of menstrual bleeding at one year of
use. This can be particularly useful in older reproductive age women with dysfunctional
uterine bleeding. 18

New Developments in Natural Family Planning:

Clearplan Easy
is an electronic fertility monitor that involves urinary testing of estrogen
metabolites which marks the start of the fertile phase and the LH surge that
takes place 36 hours before the end of the fertile phase. The results of daily
urine tests are converted into colored signals on the monitor; red for peak
fertility, yellow for intermediate and green for low fertility.

Conclusion:

There has been significant recent progress in the
field of contraception demonstrated by the current avail-ability of a multitude
of contraceptive delivery systems. Clinicians should continue their effort
of counseling patients regarding correct and consistent use of different
methods. With the advent of long acting combination hormonal methods like
the monthly injection, weekly patch and monthly ring, the historical compliance
problem with hormonal daily pills should be reduced. Since 25% of childbearing
age women rely on surgical sterilization for birth control, it is expected
that the Essure device will be widely used since it is a nonsurgical method.
The therapeutic value of Mirena progestin IUD goes beyond contraception and
has the potential to avert endometrial ablations and hysterectomies in women
with dysfunctional uterine bleeding.

REFERENCES

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14. Zacur HA, Hedon B, Mansour
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15. Zieman M, Guillebaud
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17. Randomised controlled trial of levonorgestrel
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