Oral contraceptive use in perimenopause
Andrew M. Kaunitz, MD
Jacksonville, Florida
Perimenopause represents a transition period lasting about 5 years before the permanent cessation of
spontaneous menses. During this transition, the emphasis of clinical care changes. Although women still
need effective contraception during perimenopause, issues including loss of bone mineral density, menstrual
cycle changes, and vasomotor instability also need to be addressed. Hormone replacement therapy is not
the first-line treatment for women with symptomatic perimenopause because hormone replacement therapy
neither suppresses ovulation nor provides contraception; also, it will not prevent and in fact may aggravate
unpredictable perimenopausal bleeding. Oral contraceptives offer many benefits for healthy, nonsmoking,
perimenopausal women. Oral contraceptive use by women in their 40s has been found to decrease the risk
of postmenopausal hip fractures and regularize menses in women with dysfunctional uterine bleeding,
reducing the need for surgical intervention for benign menstrual conditions. Use of oral contraceptives also
can reduce long-term risk of endometrial and ovarian cancers. There is also good evidence that oral
contraceptives relieve vasomotor symptoms in perimenopausal women. Oral contraceptives can be viewed
as a strategy not only to improve perimenopausal symptoms, provide effective contraception, and reduce
some long-term health risks, but also to enhance the quality of life for perimenopausal women. (Am J Obstet
Gynecol 2001;185:S32-7.)
Key words: Oral contraception, bone mineral density, menstrual changes, dysfunctional uterine
bleeding, vasomotor instability, triphasic norgestimate/35 µg ethinyl estradiol, monophasic
norethindrone acetate/20 µg ethinyl estradiol
Perimenopause constitutes a transition period characterized by unpredictability; 1 month does not predict the
next in terms of the menstrual cycle or other symptoms.
Overall, perimenopause occurs about 5 years before the
permanent cessation of spontaneous menses, so clinicians can anticipate that patients in their mid 40s will
begin to experience manifestations of this transition.1,2
Although the cycle length begins to shorten, the potential for ovulation and pregnancy is preserved for a number of years.1,3,4 Therefore perimenopausal women still
need effective contraception. Other issues that must be
addressed in this age group are menstrual changes, including dysfunctional uterine bleeding; vasomotor instability; and prevention of osteoporosis, cardiovascular
disease, and gynecologic cancers.
Oral contraceptive use in perimenopause
The effectiveness of oral contraceptives (OCs) is high
in perimenopausal women.5 Although perimenopausal
From the Gynecology, Menopause and Bone Density Services, Medicus
Diagnostic Center, Department of Obstetric and Gynecology, University
of Florida Health Science Center.
Reprint requests: Andrew M. Kaunitz, MD, Department of Obstetrics
and Gynecology, University of Florida Health Science Center, 653-1 W
8th St, Jacksonville, FL 32209.
Copyright © 2001 by Mosby, Inc.
0002-9378/2001 $35.00 + 0 6/0/116525
doi:10.1067/mob.2001.116525
S32
women tend to be less fertile6 and are also better
pill-takers than are younger women, they are still at risk
for unintended pregnancy and therefore require contraception. Yet only 4% of women in the United States aged
45 to 50 years reported in a recent survey that they were
using the pill.7 The dominant method used by older
women is sterilization, which has a higher long-term rate
of failure than was believed previously.8 Many older reproductive-age women are reluctant to use OCs because
they fear serious health risks such as cancer and cardiovascular disease.9-11 Another concern, not only among
teenagers but also among perimenopausal women, is
weight gain. Perimenopausal women are not likely to use
OCs successfully unless clinicians address such fears and
educate patients about the many benefits of continuing
or initiating OC use during the perimenopause.
Contraception. Many perimenopausal women fail to
appreciate the continuing need for effective contraception, yet statistics suggest that 80% of women between the
ages of 40 and 44 can conceive.12 Consequently, older
women have a high rate of unintended pregnancy. Data
from the National Survey of Family Growth show that
51% of pregnancies that occurred among women aged 40
and older during 1994 were unintended; 65% of these
unintended pregnancies ended in abortion.13 Because
lack of cycle predictability is the rule in this age group
and unanticipated ovulation may occur, contraception
must be practiced if pregnancy is not desired.1
Kaunitz S33
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Am J Obstet Gynecol
Fig 1. Incidence of breakthrough bleeding or spotting at each cycle. Asterisk, Significantly less breakthrough bleeding/spotting at each cycle with triphasic norgestimate/35 µg ethinyl estradiol versus norethindrone acetate/20 µg
ethinyl estradiol (P < .001). NGM, Norgestimate; EE, ethinyl estradiol; NETA, norethindrone acetate. Adapted from
Sulak P, Lippman J, Siu C, Massaro J, Godwin A. Clinical comparison of triphasic norgestimate/35 µg ethinyl estradiol and monophasic norethidrone acetate/20 µg ethinyl estradiol: cycle control, lipid effects, and user satisfaction.
Contraception 1999; 59:161-6. Copyright 1999, with permission from Elsevier Science.
Bone mineral density and prevention of postmenopausal osteoporotic fractures. Women attain peak
bone mineral density between ages 20 and 40, after
which age-associated losses are about 1% per year.14
Bone loss accelerates during perimenopause and
menopause,14, 15 and annual losses of 3% to 5% may
occur in the 5 years after the onset of menopause.14 One
well-established risk factor for decreased bone mineral
density is the existence of a hypoestrogenic state, such
as anorexia nervosa,14 exercise-induced amenorrhea,14
early oophorectomy,14 premature ovarian failure,14
hyperprolactinemia,14 chemotherapy or radiation therapy,16,17 and gonadal dysgenesis.18
By taking OCs, a 45-year-old woman can better maintain
her bone mineral density. Prospective studies of perimenopausal women have found that OC users can preserve bone mineral density, whereas bone loss has been
observed in nonusers.19,20 These findings suggest that premenopausal use of OCs can prevent the accelerated bone
turnover and reverse the decrease in bone mineral density
that accompany declining ovarian function.20 Moreover,
the longer the duration of exposure to OCs, the greater is
the positive effect on bone mineral density.21-24 Recently, a
large case-control study in Sweden showed that women
who took OCs in their 40s decreased their risk of postmenopausal hip fractures by 30% compared with those
who had never used OCs (Table I).25
Menstrual cycle changes. Bleeding changes represent
one of the most common reasons for which perimenopausal women consult a clinician. Such changes
Table I. Decreased hip fracture risk with oral contraceptive use
Age at oral
contraceptive use
Multivariate any
oral contraceptive
Never used
<30 y
30-39 y
≥40 y
1.0 (referent)
1.3 (0.8-2.1)
0.8 (0.6-1.2)
0.7 (0.5-0.9)
Odds ratio
(95% confidence interval)
≥50 µg ethinyl estradiol
oral contraceptive
1.0 (referent)
1.1 (0.6-2.0)
0.8 (0.5-1.1)
0.6 (0.4-0.9)
Adapted with permission from Michäelsson K, Baron JA,
Farahmand BY, Persson I, Ljunghall S. Oral-contraceptive use
and risk of hip fracture: a case-control study. Lancet 1999;
353:1481-4. ©1999 by The Lancet Ltd.
raise concerns about the presence of cancer or other
underlying disease and cause patient anxiety. Erratic
bleeding in perimenopausal women reflects the less predictable ovulatory pattern characteristic of this transition.
Usually the cycle length shortens by 2 to 7 days, although
longer cycles or irregular menses are possible.6 There are
also changes in the quality of bleeding (heavier cycles initially, then lighter flow) and spotting before menses.6
This dysfunctional uterine bleeding not only is annoying
for women but also can put them at increased risk for endometrial hyperplasia.2
For decades OCs have been used to control uterine
bleeding and regularize menses. Now there are data showing that use of a specific OC formulation regularizes
menses in women complaining of dysfunctional uterine
bleeding.26 In a double-blind, placebo-controlled, multi-
S34 Kaunitz
August 2001
Am J Obstet Gynecol
Figure available in print only
Fig 2. Oral contraceptives decrease number and severity of hot flashes in perimenopausal women. Randomized,
double-blind, placebo-controlled, 6-cycle trial. EE, Ethinyl estradiol; NETA, norethindrone acetate. Adapted with
permission from Casper RF, Dodin S, Reid RL, and Study Investigators. The effect of 20 µg ethinyl estradiol/1mg
norethidrone acetate (Minestrin), a low-dose oral contraceptive, on vaginal bleeding patterns, hot flashes, and quality of life in symptomatic perimenopausal women. Menopause 1997; 4:139-47.
Table II. Impact of low-dose oral contraceptives on lipid
profiles in premenopausal women: randomized, open-label,
6-cycle trial in women aged 18-50 years; lipid changes
baseline to final visit
Median % change
Lipid
High-density
lipoprotein–
cholesterol
HDL2
Apo A-1
Triphasic
norgestimate/
35 µg ethinyl estradiol
Norethindrone
estradiol acetate/
20 µg ethinyl estradiol
4.5%*
–4%
25%†
17.9%*
13.3%
9.8%
Adapted from Sulak P, Lippman J, Siu C, Massaro J, Godwin A.
Clinical comparison of triphasic norgestimate/35 µg ethinyl
estradiol and monophasic norethidrone acetate/20 µg ethinyl
estradiol: cycle control, lipid effects, and user satisfaction. Contraception 1999; 59:161-6. Copyright 1999, with permission from
Elsevier Science.
HDL2, High-density lipoprotein–variant 2.
*P < .001.
†P < .004.
center trial, 201 women with metrorrhagic, menometrorrhagic, oligomenorrheic, or polymenorrheic dysfunctional
uterine bleeding were randomized to receive an OC
(triphasic norgestimate/35 µg ethinyl estradiol) or
placebo for 3 cycles. For each subtype of dysfunctional
uterine bleeding, improvement was noted for subjects
treated with OCs. Overall, significantly fewer women receiving OC than those receiving placebo reported abnormal bleeding (P < .001). Regarding the effect of
dysfunctional uterine bleeding on quality of life, the
women who received OCs also had greater improvement
from baseline in physical function (eg, self-care, walking,
lifting, bending, exercise) than subjects given placebo.
Data from a 6-cycle randomized clinical trial in premenopausal women show that rates of breakthrough
bleeding with this 35-µg estrogen formulation are one
third lower than with a 20-µg estrogen formulation
(monophasic norethindrone acetate/20 µg ethinyl estradiol) (Fig 1).27 These observations provide high-quality evidence that the 35-µg estrogen OC formulated with
triphasic norgestimate represents a sensible choice for
women diagnosed with irregular bleeding, including perimenopausal women.
In addition to the treatment of dysfunctional uterine
bleeding, OCs represent an appropriate first-line therapy for primary dysmenorrhea and heavy flow/menorrhagia (including women with uterine fibroids),
although these indications for use are not approved by
the Food and Drug Administration.28-30 Rates of hysterectomy for benign menstrual conditions, particularly
fibroids and dysfunctional uterine bleeding, peak
among women in their 40s.31 Thus OCs can be viewed as
a strategy not only to improve perimenopausal symptoms, provide effective contraception, and diminish the
risk of fractures and gynecologic cancers, but also as a
way to reduce the need for gynecologic surgery for benign menstrual conditions.
Lipid profiles in women using oral contraceptives. A randomized study of women between the ages of 18 and 50
showed that the triphasic norgestimate/35-µg ethinyl
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Am J Obstet Gynecol
estradiol OC produced considerably more desirable
lipoprotein changes than the monophasic norethindrone
acetate/20-µg ethinyl estradiol OC (Table II).27 The 35-µg
ethinyl estradiol OC had significantly (P ≤ .001) greater
beneficial effects on high-density lipoprotein cholesterol,
high-density lipoprotein–variant 2, and apoprotein A-1
than the 20-µg ethinyl estradiol OC. Whether these findings are clinically relevant to the average perimenopausal
woman is not known; however, for patients with a history
of smoking or dyslipidemia and those with a family history
of premature coronary artery disease, selection of an OC
formulation that provides a more favorable lipoprotein
profile would appear prudent.
Vasomotor symptoms. Approximately 85% of perimenopausal women experience symptoms of vasomotor
instability (ie, hot flashes, night sweats, sleep disturbances).6 The intensity, duration, and frequency of these
symptoms are highly variable; some women experience
one or two hot flashes daily whereas others may have 40
per day.6 There is evidence showing that OCs relieve vasomotor symptoms in perimenopausal women.19,32 In a
3-year, prospective cohort study comparing 100 perimenopausal women treated with a triphasic OC (ethinyl
estradiol 30/40/30 µg/levonorgestrel 0.05/0.075/0.125
mg) with a similar number of age-matched untreated
women, 90% of the OC users obtained complete relief of
vasomotor symptoms after 2 months’ use, and the remaining 10% responded after 3 months.19 By contrast,
60% of untreated women had no improvement in vasomotor symptoms during these 3-month observations. The
failure to use blinding or a placebo group, however, limits the credibility of this study’s findings.
A placebo-controlled, double-blind, randomized, parallel group study in 132 perimenopausal women showed
that a low-dose, monophasic OC (20 µg ethinyl estradiol/norethindrone acetate 1 mg) also decreased hot
flashes.32 Among the 65% of subjects who experienced at
least one hot flash daily (38 OC, 36 placebo), OC users
experienced approximately 50% fewer hot flashes over
the 6-month study period than placebo users (Fig 2). Similarly, the mean severity (rank: mild = 1, moderate = 2, severe = 3) of hot flashes among OC users was half that of
placebo users; mean severity scores were 66.9 and 131.2,
respectively. However, these differences were not statistically significant in this small clinical trial.
Evaluation and management of perimenopausal
women
Prevention of cardiovascular disease. Clinical experience suggests that the perimenopausal woman is much
more receptive to recognizing her own mortality than are
teenage girls, many of whom consider themselves invulnerable. Older women recognize that cardiovascular risk
reduction is important; they will pay closer attention to
lifestyle issues such as smoking cessation, diet, exercise,
Kaunitz S35
Table III. Benefits of oral contraceptive use in perimenopausal women
Effective contraception (if needed)
Treatment of irregular menses/dysfunctional uterine bleeding, menorrhagia, and/or dysmenorrhea
Reduction in vasomotor symptoms
High bone density/fewer fractures
Prevention of ovarian and endometrial cancers
Treatment of acne
and weight control to achieve reductions in cardiovascular risk. The guidelines of the American College of Obstetricians and Gynecologists indicate that regular
cholesterol screening every 5 years is appropriate in this
age group.33
Prevention of bone loss. As with cardiovascular disease,
lifestyle issues are key factors in maintaining good bone
mineral density before menopause and preventing postmenopausal fractures. Adequate dietary intake of calcium and vitamin D, avoidance of excess alcohol or
caffeine, smoking cessation, and weight-bearing exercise
all represent important strategies to prevent bone loss in
perimenopausal women.33,34 Selective use of bone density testing, on the basis of the presence of risk factors, is
recommended. As indicated earlier, OCs can provide a
powerful tool for maintaining or even increasing bone
mineral density in women in their 40s and for preventing
fractures later in life.
Prevention of cancers. Cancer screening and prevention are primary considerations among perimenopausal
women. After 3 consecutive annual normal cervical cytology screenings in a patient at low risk, clinicians may use
their own discretion to determine when another screening is necessary.33 All dysfunctional or abnormal bleeding
should be evaluated in the office by endometrial sampling to rule out the presence of endometrial hyperplasia.2,35 Different professional societies have varying
recommendations for mammographic screening in the
fifth decade of life. The American College of Obstetricians and Gynecologists recommends mammography
every 1 to 2 years until age 50 and yearly thereafter.33 Although women are more focused on prevention of gynecologic cancers, colorectal cancer is the third leading
cause of cancer-related deaths in women (after lung and
breast cancer).36 Clinicians need to increase patient
awareness of colon cancer and colon cancer screening,
especially because the incidence of this cancer increases
with age.36 The American College of Obstetricians and
Gynecologists recommends fecal occult blood testing for
routine screening, and sigmoidoscopy every 3 to 5 years
after the age of 50.33 Alternatively, colonoscopy can be
performed at age 50 and, if the result is negative, repeated every 5 years. Over the next decade, colonoscopy,
because of its superior sensitivity, may become the screening test of choice for colon cancer.37 The anchorwoman
Katie Couric’s historic television broadcast of her March
S36 Kaunitz
2000 colonoscopy likely raised consciousness regarding
colon cancer screening among many women in the
United States.
Hormonal management of perimenopausal symptoms.
Clinicians are becoming increasingly aware that conventional menopausal hormone replacement therapy (HRT)
is not first-line therapy for perimenopausal women. Because HRT does not suppress ovulation, it does not provide
contraception and will not prevent unpredictable perimenopausal bleeding. In terms of osteoporosis prevention, HRT may have a less favorable impact on femoral
neck bone mineral density than OCs.38 Moreover, OCs
offer several additional benefits to perimenopausal women
(Table III). As discussed earlier, treatment of benign menstrual conditions is very important for perimenopausal patients, as are reduction in vasomotor symptoms,
stabilization of bone mineral density with prevention of
later fractures, and other noncontraceptive benefits.
Women of all ages are concerned about weight gain,
and 53% of those aged 35 to 45 believe that OC use
causes weight gain.39 However, a pooled analysis of data
from two recent double-blind, randomized, placebocontrolled clinical trials found otherwise. A total of 228
women were randomized to a triphasic triphasic norgestimate/35-µg ethinyl estradiol OC, whereas 234 received placebo for up to 6 cycles; weight gain was the
same in both groups, reported by only about 2% of subjects in each group.40 Similar data from the Postmenopausal Estrogen/Progestin Interventions trial
showed that women randomized to oral conjugated
equine estrogen therapy (0.625 mg/d) with or without
added progestin gained 1.0 kg less on average at the end
of 3 years than those assigned to placebo (P = .006).41
Nevertheless, it is a difficult task to inform women that
the use of OCs or HRT will not cause excess weight gain.
When should a perimenopausal woman receiving OCs
be transitioned to HRT? Traditionally, reproductive endocrinologists have advised that levels of follicle-stimulating hormone should be measured during the pill-free
interval. However, a single follicle-stimulating hormone
assessment to determine menopausal status is unreliable.42-46 Furthermore, when women of this age are using
OCs, follicle-stimulating hormone levels remain suppressed, not for just 1 week but for many weeks after discontinuation, making follicle-stimulating hormone
testing even less predictive in this setting. A preferable approach is to continue combination OCs in healthy nonsmoking women until age 55 or older, when the
probability of permanent cessation of ovulation is high.
As menopause is reached, women can be transitioned
from OCs to HRT, if they so choose, without any pill-free
days or the need for expensive laboratory tests that are
not dependable. New HRT formulations allow perimenopausal women receiving OCs transitioning to HRT
to continue using the same progestin.
August 2001
Am J Obstet Gynecol
Conclusions
For women and their clinicians, the perimenopausal
transition signals a time of changing clinical emphasis
and lifestyle. Because benign menstrual disorders are
common in this age group, their prevention and treatment is a primary issue. Women in their 40s are more willing than younger women to focus on disease prevention
and may likewise be more receptive to making the
lifestyle modifications needed to reduce the risk of cardiovascular disease, as well as to prevent bone loss. They
also are more highly motivated to participate in routine
cancer screening programs. For many perimenopausal
patients, OCs containing 30 to 35 µg ethinyl estradiol
represent a sound choice, and studies have shown that
one such formulation, triphasic norgestimate/35 µg
ethinyl estradiol, regularizes dysfunctional bleeding, provides good cycle control, has a favorable impact on the
lipoprotein profile, and does not cause weight gain. By
educating perimenopausal patients about the contraceptive and noncontraceptive benefits of OCs, clinicians can
help many more women in their 40s to initiate and remain on OCs. Such education also provides an opportunity to help women anticipate menopause and weigh the
pros and cons of future HRT.
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