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Mary
V.
Seeman,
Ruth
Ross
Prescribing
contraceptives
for
women
with
schizophrenia.
Journal
of
Psychiatric
Practice
2011;
17(4):258-‐269.
DOI:
10.1097/01.pra.0000400263.52913.dc
1
Contraceptives
Abstract
Although women with serious mental illness have high rates of lifetime sexual partners,
they infrequently use contraception. Consequently, the prevalence of unwanted pregnancies
and sexually transmitted infection is high in this population. The objective of this paper is
to help clinicians recommend appropriate contraception to women with schizophrenia. The
authors reviewed recent literature on the use of contraceptive methods by women with
schizophrenia treated with antipsychotic and adjunctive medications. Contraceptive
counseling to women and their partners is an important part of comprehensive care for
women with serious and persistent mental illness. Women with schizophrenia who smoke,
are overweight, or have diabetes, migraine, cardiovascular disease, or a family history of
breast cancer should be offered non-hormonal contraception. Women with more than one
sexual partner should be advised on barrier methods in addition to any other contraceptive
measures they are using. Clinicians should be alert for potential interactions among oral
hormonal contraceptives, smoking, and therapeutic drugs. Long-lasting contraceptive
methods, such as intrauterine devices, progesterone depot injections, or tubal ligation are
reasonable options for women having no wish to further expand their families.
2
Contraceptives
Very few women with a diagnosis of schizophrenia ask their psychiatrists for contraceptive advice
and very few psychiatrists prescribe these medications. Yet unintended pregnancies in this
population have a major impact on the health of women and children, and on the cost of healthcare.
A recent study identified a number of barriers that may hinder clinicians from providing
contraceptive advice to their patients,1 including lack of contraceptive knowledge, insufficient
training, discomfort with the subject,2 and incorrect assumptions about pregnancy risk. For
example, psychiatrists may view patients with schizophrenia as asexual or too socially isolated for
interpersonal sex3 or they may wrongly believe that antipsychotic medication protects their patients
against pregnancy.4 They may also have negative perceptions of contraceptive methods or they may
prefer to wait for patients to introduce the topic. They may also see contraceptive counseling as
peripheral to the psychiatric role, delegating such discussions to the family physician, even though
many patients with schizophrenia do not see a family physician. It is also possible that discussing
contraception with psychiatric patients invokes distressing images of a bygone era when psychiatric
patients were sterilized against their will.5
Nevertheless, women who use mental health services have sexual and reproductive service
needs.6 Based on a 2009 review of 84 studies on reproductive health in women with serious mental
illness, Matevosyan concluded that the rate of lifetime sexual partners in this population is high
compared with other populations, that contraceptive usage is relatively low, and that there are high
rates of both unwanted pregnancies and sexually transmitted infections in this population.7 These
findings underscore the need for physicians to develop the skills needed to address contraceptive
and sexual safety issues with their patients. This selective review provides a brief overview of the
literature on this subject and presents clinical recommendations.
BACKGROUND
3
Contraceptives
Over 90% of the women (n = 233) reported having an active sexual life. Forty women had had their
tubes tied, mostly through their own choice, but, in 6 cases, a physician, partner, or family member
had made the decision. Of those using contraceptives (n = 35), most (n = 22) reported using oral
contraceptives, while the rest used condoms (n = 11) or an injectable contraceptive (n = 2).
However, and this speaks to inadequate counseling, almost 80% were judged to be using their
chosen method incorrectly. The rate of unplanned pregnancies in this study was high, partly, the
authors suggest, due to drug interactions between hormonal contraceptives and therapeutic drugs
that reduced the effectiveness of the contraceptives. These researchers concluded that the use of
contraceptive methods that require personal control is problematic for psychiatric patients and that
partners and/or family members need to be included in discussions about contraception.10
A systematic review of the published literature on sexually transmitted diseases (STDs) in
persons with chronic mental illness found many information gaps with respect to prevalence. 11
Although most patients with schizophrenia express concern about the risk of contracting infections
during sexual intercourse, they also report engaging in relatively unsafe sexual behavior and not
complying with contraceptive measures.12
Clinical and Social Implications of Unwanted Pregnancy and Sexually Transmitted Diseases
Unwanted pregnancy and infection, if not prevented, bring hardship not only to the woman herself
but also to her offspring. Unwanted pregnancy predicts schizophrenia-spectrum disorders in
offspring of mothers with psychosis.13 Maternal infection during pregnancy is also associated with
schizophrenia in offspring. 14,15
4
Contraceptives
of rape, since sexual assault is not rare in this population.17 Some patients, for various reasons, are
afraid to take contraceptive pills.
CONTRACEPTIVE METHODS
Many types of contraceptive methods are currently available. Psychiatrists need to be
knowledgeable about existing methods so that they can counsel their patients appropriately.18 The
following sections present a concise overview of the different methods in terms of their benefits,
drawbacks, and issues related to their use in women with schizophrenia.
Abstinence
Benefits. Sexual abstinence protects against both pregnancy and sexually transmitted disease.
Issues for women with schizophrenia. Abstinence is often the method that women with
schizophrenia opt for when they do not have a male partner and do not expect to have one. The
problem is that they may unexpectedly meet a partner or they may be the victim of non-consensual
sex.
Benefits. Women may prefer to use natural methods and, when properly used, they are very
effective, a fact that physicians may underestimate.19 Natural birth control may be a good option for
women with committed partners and women whose religious faith does not permit the use of other
methods.
Drawbacks. In order for natural methods to be effective, women need to know how to use them
correctly.20 Also, in order to educate patients about these methods, physicians themselves need to
understand them.21
5
Contraceptives
Issues for women with schizophrenia. The calculations involved may be too demanding for many
women, especially women with cognitive impairment such as is often present in schizophrenia.
Rhythm methods may not be effective in this population if antipsychotic drugs disrupt, as they often
do, the regularity of menstruation. These methods also offer no protection against STDs.
Benefits. Many women prefer female barrier methods since their use does not rely on the male
partner.
Drawbacks. Advance planning before intercourse is needed. The various female barrier methods
have a 15%--30% failure rate. Some barrier methods require fitting and maintenance and all of
these devices require some skill and experience to insert properly. Allergies to spermicides are not
rare. It has also recently been shown that spermicides may increase the risk of HIV infection,24
although new spermicides that can protect against STDs are being developed.25 Cost may also be an
issue with these methods.
Issues for women with schizophrenia. Women with schizophrenia may have difficulty ensuring
proper maintenance and use of barrier contraceptives, as well as lacking sufficient executive
functioning to plan for their use in advance.
6
Contraceptives
Drawbacks. The efficacy of condoms depends on the full co-operation of the male partner. Non-
latex condoms (for use when allergies develop to latex) have a greater failure rate than latex ones
for both infection and contraception.
Issues for women with schizophrenia. Women with schizophrenia have difficulty insisting that
their male partner wear a condom.
Vasectomy
A permanently committed male partner can undergo vasectomy. Couple sessions are indicated to
discuss this option, which would be ideal for a monogamous woman with schizophrenia.
Benefits. Oral birth control pills are 97%--99.9% effective if used correctly and consistently.
Hormonal contraceptive methods can stop menstruation for long periods, even indefinitely, a
feature that many women like. Remembering to take the pill daily is facilitated by the provision of
monthly packs.
Drawbacks. The pill does not protect against STDs, so the use of an accompanying barrier method
is required. Cost may be an issue if the woman has no insurance. Side effects, most of them caused
by the estrogen component of the pill, are concerns, especially in women who smoke, are
7
Contraceptives
overweight, suffer from diabetes, or heart disease, or are at risk for breast cancer. Some women
taking low-dose oral contraceptive pills also complain of decreased libido and arousal because of
the decrease in testosterone, and some develop dyspareunia.29 A potentially serious side effect is
vascular thrombosis, the risk of which is increased by estrogen-containing pills. It is important to
note that oral contraceptives are not associated with an increased long-term risk of death. In fact, a
net benefit was found in a recent large cohort study from the United Kingdom.30 The balance of
risks and benefits, however, may vary globally, depending on patterns of oral contraception usage
and background risk of disease.30,31 To be safe, women 35 years of age and older should be assessed
for cardiovascular risk factors including hypertension, smoking, diabetes, nephropathy, and other
vascular diseases, including migraines, prior to use of oral contraceptives.32
Issues for women with schizophrenia. For women with schizophrenia, taking a daily contraceptive
may reinforce the daily routine of taking their antipsychotic medication and may thus prove helpful
for treatment adherence, although there is no evidence of this. At the same time, remembering to
take the pill daily can be a challenge for women who do not have a daily routine.
Hormones can also interact with therapeutic medications to reduce the effectiveness either
of the contraceptive or the therapeutic agent (see discussion of Drug Interactions later in this
article).
Physicians often underestimate the impact of contraceptive methods on sexual function,
which is especially problematic for women with schizophrenia whose libido is already low because
of the medications they are taking.33
Comorbid conditions that can present problems for use of the pill, such as smoking,
obesity, diabetes, and other cardiovascular risk factors, are not rare in women with schizophrenia.
The freedom of sexual activity without pregnancy is the main advantage, but there is also potential
benefit of estrogen for schizophrenia symptoms themselves. Accumulating evidence from clinical
data and basic and experimental research, as well as epidemiologic studies, suggests that estrogens
exert therapeutic effects in schizophrenia. The onset of schizophrenia in women is about 5 years
later than in males and this has been attributed to the protective effect of estrogen. Women are
especially vulnerable to relapse of existing illness during the postpartum period when estrogen
levels have decreased, and at menopause. Severity of symptoms has also been observed to fluctuate
with menstrual cycle phases, increasing during low-estrogen phases. Intervention studies using
estrogen as a therapeutic agent have provided further support for the hypothesis that estrogen
modulates the expression of psychotic symptoms. 34—36 This, of course, must be balanced against the
known side effects and risks of hormones. The risk of vascular thrombosis is increased both by
8
Contraceptives
estrogen-containing pills and by antipsychotic medication. Estrogen use is usually considered a risk
for venous thrombosis, whereas smoking, hypertension, diabetes, the metabolic syndrome, and
hyperlipidemia (all of which can be aggravated by antipsychotics) are thought to be risks for arterial
thrombosis. A number of recent studies have recently challenged this dichotomy, and it is now
recognized that venous and arterial thromboses share risk factors and both can lead to
cardiovascular stroke.37--39
Physiologic and pharmacologic interactions between obesity and contraceptive steroids can
occur,40 which is a particular concern for women with schizophrenia, given the weight-inducing
effects of some antipsychotic medications. Obesity may result in lower blood levels of steroid
contraceptives, but the effect is thought to be relatively small. Of three studies that examined body
mass index and pregnancy rates in women taking combination oral contraceptives, only one found a
greater risk of pregnancy in overweight and obese women.41,42
Progesterone-only Contraceptives
Progesterone-only pills and long-acting progesterone injections (medroxyprogesterone acetate or
Depo-Provera) are also available.43 Depo-Provera is given every 3 months as a 150 mg
intramuscular injection.
Benefits. Depo-Provera is a very effective contraceptive, with a failure rate of less than 1%. It has
no appreciable effects on blood pressure, cholesterol, triglycerides, or thrombosis risk, an important
advantage. No significant adverse effects on growth and development have been found in children
exposed to DepoProvera. No major delays in return to fertility after stopping the injection have been
observed. The injections are not associated with any increased risk of ovarian, liver, or cervical
cancer, while the risk of endometrial cancer may be reduced.
Drawbacks. To be fully effective, the progesterone-only pill has to be taken within the same 3 hours
each day. Progesterone-only methods all cause some degree of menstrual disturbance (e.g., break-
through bleeding). They can also infrequently decrease libido and cause dyspareunia.33
DepoProvera njections are associated with weight gain, can increases truncal fat deposition, and
have been found to lowers glucose tolerance in women with diabetes.44 The injections are also
temporarily irreversible during their 3 month duration, which is a concern if problematic side effects
develop. An increased risk of breast cancer has been observed, which could be due to higher rates of
detection. Bone mineral density is decreased and there is a slightly increased risk of fractures,45
which can be decreased by not smoking and increasing calcium intake.46
9
Contraceptives
Issues for women with schizophrenia. The need to take the progesterone pill during the same time
period each day places considerable strain on women who lead irregular lives. Although they may
not enjoy needles, for women with schizophrenia who have difficulty managing other birth control
methods, an injection every 12 weeks may be ideal (but it does not protect them from sexually
transmitted disease).
Hormones can also be delivered by skin patch or subdermal implant, vaginal ring or transdermal gel
or spray. The skin patch is applied weekly for 3 weeks with 1 week off. The implant is a rod
inserted under the skin by a physician that can stay in place for up to three years. Implant removal is
technically more difficult and time-consuming than insertion. These methods are uncomfortable for
some women and they do not, of course, protect against STDs. Patches, rings and subdermal
implants are 97%--99% effective in preventing pregnancy. The hormones in patches, rings, and
implants bypass the liver and therefore are not subject to drug interactions via metabolism by liver
enzymes.
Issues for women with schizophrenia. Some women will prefer long-lasting methods that do not
require coming in for injections every 12 weeks although cost will be a problem in this population.
Intrauterine
Devices
Intrauterine devices (IUDs) are placed within the uterus by a physician. The best-known IUDs
contain copper, but progestin-impregnated IUDs (e.g., levonorgestrel IUD) are also available.
Current evidence suggests that hormonally impregnated IUDs are somewhat more effective in
preventing pregnancy than copper IUDs, although it depends on the specific devices being
compared. Continuation of use is similar among hormonal and non-hormonal IUDs.47
Benefits. Like hormones in patches, rings, and implants, hormones in IUDs bypass the liver and
therefore are not subject to drug interactions via metabolism by liver enzymes. IUDs have similar
contraceptive efficacy as combined oral contraceptives when those are used correctly, but are more
effective than oral contraception that is incorrectly used. Unfortunately, a recent study suggested
that women receive comparatively little information about IUDs.48 Problems such as difficult
insertion, pain, bleeding, and syncope are reported in less than 1.5% of cases. A copper IUD is a
10
Contraceptives
first-line contraceptive method for women with a history of deep venous thrombosis, pulmonary
embolism, or heart disease. It provides contraception for up to 10 years, with annual pregnancy
rates of less than 1 per 100 woman-years.49
Drawbacks. IUDs can be accidentally expelled from the body, sometimes without the person
realizing it. This has been reported to occur in about 5% to 10% of cases within 5 years of insertion,
and expulsion recurs in about 30% of cases. Condoms have to be used as well as the IUD to prevent
infection with sexual transmitted diseases. Although the rare intrauterine pregnancies that occur in
women using an IUD generally end in miscarriage, approximately 1 in 20 of these pregnancies is
ectopic. Uterine perforation during insertion is rare, but does occur in 0.6 to 16 per 1000 insertions
regardless of type of IUD. The risk of perforation is higher when the IUD is inserted less than 4 to 6
weeks after delivery or abortion. During the first 3 months after insertion, the risk of pelvic
infection is slightly higher than in the general population, with approximately 6 pelvic infections
per 1000 woman-years of IUD use expected. Menstrual bleeding is often heavier in women with
copper IUDs than in women who do not use IUDs, and may be accompanied by pain. The
levonorgestrel IUD tends to reduce menstrual blood loss but can cause irregular bleeding;
amenorrhoea occurs in 35% of women after 2 years of use. The levonorgestrel IUD may also have
adverse effects such as headache, acne, breast tension, and functional ovarian cysts.
Issues for women with schizophrenia. IUDs have been recommended as the most suitable
contraceptive system for women with chronic illness because they are long-lasting and require little
attention. This is especially true when the woman does not intend to become pregnant in the near
future and finds planning and remembering to take daily pills difficult.50 A chart review comparing
uses of IUDs and Depo-Provera in high risk women found that the women with IUDs were more
likely to report side effects but were less likely to discontinue use.51
Emergency Contraception
Because sexual activity is often unplanned and unpredictable among women with schizophrenia,
emergency contraception (EC) is a necessary back up. Concerns about the mechanisms of action of
EC methods are a major barrier to the widespread acceptance and use of EC. Women need to be
educated that EC pills are contraceptives, not aborticants. EC is available without a prescription and
several forms are now available.52 EC is safe and reduces the risk of pregnancy by 75%--89%. The
most widely used EC is levonorgestrel (LNG) in a single dose of 1.5 mg taken within 120 hours of
unprotected intercourse. LNG-EC delays or inhibits ovulation but has no effect once luteinizing
hormone has been released.53 It is possible to obtain the same effect by taking several regular
11
Contraceptives
combined oral contraceptive pills, an off-label use approved by the U.S. Food and Drug
administration. Ulipristal acetate was approved as EC in the United States in 2010. It also works for
up to 120 hours after intercourse.54 The copper intrauterine device (IUD) is also highly effective as
an emergency contraceptive but requires insertion by a skilled healthcare provider. If a woman is
already pregnant, EC will not harm the fetus. Temporary side effects include nausea or vomiting.
Less common side effects are headache, breast tenderness, dizziness, fluid retention, mood changes,
or abdominal cramps. These side effects rarely last more than 2 days. The next menstruation can
come later than expected.
Abortion Pills
Administration of mifepristone followed by the prostaglandin, misoprostol, has been used
successfully in the medical termination of pregnancy for over 25 years, and the method is registered
in 35 countries. However, mifepristone is not approved for emergency contraceptive use in the
United States because understanding of its mechanism of action is incomplete. Unlike other EC,
mifepristone can terminate established pregnancies.55
Surgical Methods
Surgical contraception, therapeutic abortion, and sterilization are problematic methods because of
religious, moral, and ethical concerns. Nevertheless, many countries still advocate voluntary
sterilization for women with serious mental illness. The important issue is to ensure that the woman
making the decision is fully informed of consequences and is fully competent to make the decision.
Surrogate consent is sometimes necessary but should be avoided if possible. Therapeutic abortion is
not available in many jurisdictions and may be contrary to the woman’s personal convictions and
those of her healthcare provider or institution; in these latter cases, second opinions should be
requested.
Summary of Effectiveness
Table 1 summarizes the main advantages and disadvantages of the different contraceptive methods
for women with schizophrenia. The hierarchy of contraceptive effectiveness in descending order
is:56
1. Female sterilization and long-acting hormonal contraceptives (IUDs and implants)
2. Larger copper IUDs
3. Smaller copper IUDs and short-acting hormonal contraceptives (injectables, oral
contraceptives, patch, vaginal ring)
12
Contraceptives
· Is the level of the concomitant drug increased sufficiently so that side effects will develop
or is it decreased sufficiently to undermine its efficacy?
· Is the level of the contraceptive reduced sufficiently so that it will no longer prevent
conception?
Anti-epileptic agents. The most notable interactions involve antiepileptic drugs (AEDs), which are
sometimes used as adjunctive agents in the treatment of schizophrenia or to prevent side effects of
antipsychotics.58 Combined oral contraceptives lower the levels of both valproate and lamotrigine
making them less effective.59,60 On the other hand, many AEDs (phenobarital, phenytoin,
carbamezapine, felbamate, oxcarbazepine and topiramate induce cytochrome P450 3A4, leading to
enhanced metabolism of either or both the estrogenic and progestogenic components of oral
contraceptives, thereby reducing their efficacy in preventing pregnancy.61 Benzodiazepines,
gabapentin, lamotrigine, valproic acid, levetiracetam, tiagabine, zonisamide and ethosuximide are
not associated with clinically significant pharmacokinetic interactions.62,63
Antipsychotic medications. When combination oral contraceptives are taken together with the
antipsychotic drug clozapine, which is metabolized by 3A4, 1A2, and 2C19, there is a significant
increase in clozapine blood levels, with levels almost tripling. This can result in important side
effects, including hypotension, sedation, tremor, and nausea.64 The same effect occurs when
combination oral contraceptives are combined with the antipsychotic chlorpromazine.65,66
Discontinuing contraceptives during the course of treatment with one of these antipsychotics
decreases clozapine or chlorpromazine blood levels, necessitating a compensatory increase in the
antipsychotic dose in order to maintain a therapeutic blood level. While the antipsychotic
ziprasidone is also metabolized by CYP 3A4, it does not appear to significantly inhibit this enzyme
at clinically relevant concentrations,67 so that dose adjustments are only needed for clozapine and
chlorpromazine when taken with oral contraceptives.
SMOKING
Many women with schizophrenia smoke, and pharmacodynamic interactions between nicotine and
13
Contraceptives
estrogen can produce serious adverse cardiovascular effects.68 The use of hormonal contraceptives
of any kind in women who are 35 years of age or older and smoke 15 or more cigarettes daily is
contraindicated. It has been proposed that smoking causes “sticky fibrin” to develop, which leads to
thrombotic events.69 Although smoking does not reduce the efficacy of oral contraceptives, the level
of many antipsychotics is reduced by smoking. When a woman stops smoking, the blood levels of
these antipsychotics rise. Contraceptives can also cause levels of some antipsychotics (clozapine
and chlorpromazine) to rise, which can lead to an increase of side effects.
CLINICAL RECOMMENDATIONS
Psychiatrists need to address contraception during regular psychiatric visits with all seriously ill
women in their reproductive years. Partners should also be invited to join these discussion.
14
Contraceptives
Contraceptive options can be revisited periodically in individual, family, and group settings. Non-
hormonal contraceptive measures should be recommended for women who smoke, who are
overweight or have diabetes, migraines, or cardiovascular disease, or who have a family history of
breast cancer. To prevent against infection with STDs, women with more than one sexual partner
should be advised to use barrier methods in addition to any other contraceptive measures they are
using. Clinicians should be alert for interactions among contraceptives, smoking, and therapeutic
drugs, especially when starting or stopping oral hormonal contraceptives. Long-lasting
contraceptive methods, such as IUDs, progesterone depot injections, or tubal ligation, are
reasonable options for women having no wish to further expand their families. Finally,
contraceptive counseling is an important part of comprehensive care for serious and persistent
mental illness.
15
Contraceptives
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