7/28/2019 Smoking Lowers the Age at Natural Menopause
Among.1
1/2
Menopause: The Journal of The North American Menopause
SocietyVol. 19, No. 2, pp. 119/120DOI:
10.1097/gme.0b013e3182426af9* 2012 by The North American Menopause
Society
EDITORIAL
Smoking lowers the age at natural menopause among smokers
and raises important questions
Menopause refers to the permanent cessation of
menses. Natural menopauseVthat is, menopause
that is not caused by surgery, chemotherapy, or
radiationVis a landmark event in a womans life and in
womens health, but it is impossible to know precisely when
it has occurred because it can only be defined
retrospectively
after 12 months have elapsed since the last menstrual
period.
Many of the questions that women may have about meno-
pause could arise before menopause actually occursVthat is,
during the menopausal transition. Large, methodologically
rigorous, and multidisciplinary studies such as the Study of
Womens Health Across the Nation (SWAN) are now pro-
viding a clearer picture of the menopausal transition. On
av-
erage, that transition starts at around age 47 years and
lasts
for approximately 4 years.1 During the menopausal
transition,
hot flashes, sleep disturbances, vaginal dryness, and dyspa-
reunia, as well as other symptoms that could be caused by
menopause or aging, can emerge and persist in ways that
markedly affect quality of life.2
In this issue of Menopause, Sun et al3 report the results of
a meta-analysis that shows that smokers undergo menopause
at younger ages than nonsmokers do.
3
Previous publicationshave addressed this association, but few
have attempted to
quantify it; the meta-analysis of Sun et al3 included data
from
11 reports with sufficient detail to calculate a summary
mea-
sure. Among six studies that measured age at menopause on a
continuous scale, the weighted mean difference in age at
natural
menopause between smokers and nonsmokers wasj1.12 years
(95% CI, j1.80 to j0.44 y). That is, menopause occurred
1.12 years earlier among smokers than nonsmokers, and that
difference was statistically significant. Among five studies
that
only provided categorical ages at natural menopause, smokers
were 26% more likely (95% CI, 9%-40%) than nonsmokers
to have become postmenopausal before age 50 years (ie,
Bearly[ natural menopause) than at or after age 50 years
(ie,Blate[ natural menopause). Sun et al3 identified
significant
heterogeneity between studies, assessed the potential effects
of
that heterogeneity, and concluded that the overall results
were
robust. Similarly, they found no evidence of publication
bias
among the included studies.
Meta-analysis can serve one of two important functions.4
The first is to use the large sample size obtained through
combining studies to generate a (more) precise measure of
association between exposure and outcome. Most published
meta-analyses fall into this category. These meta-analyses
are
most useful when the previously published studies had small
sample sizes, were limited by low statistical power, or gen-
erated imprecise measures of association that raised
questions
about whether the association was spurious or potentially
real.
Previous publications had reported that age at natural meno-
pause was approximately 1 year lower among smokers than
nonsmokers,2 but this new meta-analysis by Sun et al3
further
solidifies that difference to be 1.12 years, or
approximately
13.5 months. The second purpose of a meta-analysis is to use
the collection of combined study datasets to identify
factors
within studies that generated heterogeneity across studies.
Fewer meta-analyses pursue just this second function, and
ideally, most meta-analyses would include aspects of both.4
Sun et al3 did just that by presenting different summary
mea-
sures for studies with categorical versus continuous ages at
natural menopause and by conducting sensitivity analyses to
account for potential heterogeneity.
The analysis of Sun et al3 was based on a simple dichotomy
of ever smokers versus never smokers. A 2008 systematic
review of 109 studies reported that virtually every study
that
has examined this question found a lower age at natural
menopause among current smokers than nonsmokers, butit is less
clear whether there is a dose-response between
increased smoking exposure (eg, longer durations or more
intense smoking) and younger age at natural menopause.5
Two recent studies reported that the association with age
at natural menopause was driven by current smoking, rather
than by prolonged or more intense smoking.6,7 This could re-
flect measurement error: ever smoking and current smoking
are relatively easy to recall and report, but details on how
many cigarettes were smoked and when may be more prone to
inaccurate recall and reporting. Therefore, there remains a
need for studies to evaluate current versus former smoking,
duration of smoking, intensity of smoking, and exposure to
passive smoke in more detail. Progress there could provideuseful
information for women and their healthcare providers
as well as uncover clues about the potential mechanisms be-
hind this association.
A key question is how generalizable the findings from
Sun et al3 are. Most of the studies included in the
meta-analysis
of Sun et al3 included only white women, but there is a
grow-
ing body of evidence to suggest that the timing of and symp-
toms associated with menopause can vary across racial/ethnic
groups.8 Some of these differences are cultural and social,
but
others almost certainly have genetic and biologic
components.
Menopause, Vol. 19, N o. 2, 2012 119
Copyright 2012 The North American Menopause Society.
Unauthorized reproduction of this article is prohibited.
7/28/2019 Smoking Lowers the Age at Natural Menopause
Among.1
2/2
Meta-analyses are, of course, limited by the data and
studies
that are available at that time, but future studies should
continue
to address these differences.
Studies such as SWAN have shown that menopause itself
and the age at which it occurs are the culminations of a
dynamic transition marked by menstrual cycle irregularity, a
range of potential symptoms, and the potential for difficult
decision-making regarding the risks and benefits of meno-pausal
hormone therapy, which is the most effective treat-
ment of menopausal symptoms.2 Smokers reach the end of
that transition 1 year earlier than nonsmokers do, but what
happens along the way? Does the menopausal transition begin
sooner among smokers than nonsmokers? Is the meno-
pausal transition shorter among smokers than nonsmokers?
Are symptoms or responses to treatment affected by smoking?
Because symptoms can persist after menopause, are post-
menopausal symptoms among smokers any different from
postmenopausal symptoms among nonsmokers? Indeed, the
overall predictors of the trajectory of the menopausal tran-
sition are not well understood: den Tonkelaar et al9
reported
that a later age at menopause was not associated with the
duration of the menopausal transition.9 Using data from the
SWAN, Gold et al10 reported that passive smoking but not
current smoking was associated with a higher prevalence of
vasomotor symptoms at baseline10 and that current smoking
was associated with increased frequency of symptoms during
follow-up.8 Could this indicate that the biologic mechanisms
behind the symptoms are also accelerating the transition to
menopause? The more complete picture of the menopausal
transition that is now available should permit innovative
studies of how smoking affects that transition, from start
to
finish.
Another unresolved question is what a smokers youngerage at
natural menopause means for her overall health after
menopause. As noted by Sun et al,3 age at natural menopause
is associated with health outcomes that are clearly
associated
with smoking. An earlier natural menopause increases the
risk of cardiovascular disease, venous thrombosis, and
osteo-
porosis and increases the risk of overall mortality by
approx-
imately 2% per year, but it also decreases the risk of
breast,
uterine, and hepatocellular cancers. The decline of endoge-
nous estrogens associated with earlier menopause is con-
sidered a probable mechanism for those risks, and the
antiestrogenic properties of smoking have been suggested as
a
reason for the earlier menopause among smokers, although
some recent data contradict that view.10
Does the combinationof earlier estrogen withdrawal and current
smoking further
increase a womans risk of cardiovascular disease, venous
thrombosis, or overall mortality? Better data on these ques-
tions could identify new opportunities for primary, second-
ary, and tertiary prevention that improves overall health
status among postmenopausal women.
Quitting smoking is still the best thing a smoker can do
for her health. The results from Sun et al3 provide more
evi-
dence that if a woman who smokes has not quit smoking by
the time she reaches menopause, her menopause is likely tohave
occurred roughly 1 year earlier than it would have had
she not smoked. What the 1-year difference in age at natural
menopause meant for her menopausal transition and what it
means for her future postmenopausal health are important
questions to answer.
Acknowledgments: I dedicate this commentary to the late
MaryFranR. Sowers, PhD, a mentor whose work I admired and whose
con-tributions to womens health were numerous and substantial.
Financial disclosure/conflicts of interest: None reported.
James V. Lacey Jr., PhDDepartment of Population SciencesBeckman
Research InstituteCity of Hope, Duarte, California
REFERENCES
1. McKinlay SM. The normal menopause transition: an
overview.Maturitas 1996;23:137-145.
2. Col NF, Fairfield KM, Ewan-Whyte C, Miller H. In the clinic.
Meno-pause. Ann Intern Med2009;150:ITC4-1-ITC4-15; quiz
ITC4-16.
3. Sun L, Tan L, Yang F, et al. Meta-analysis suggests that
smoking isassociated with an increased risk of early natural
menopause. Menopause2012;19:126-132.
4. Rothman KJ. Meta-analysis. In: Rothman KJ, Greenland S, eds.
Mod-ern Epidemiology, 2nd ed. Philadelphia, PA: Lippincott-Raven,
1998:643-673.
5. Parente RC, Faerstein E, Celeste RK, Werneck GL. The
relationshipbetween smoking and age at the menopause: a systematic
review.Maturitas 2008;61:287-298.
6. Kinney A, Kline J, Levin B. Alcohol, caffeine and smoking in
relationto age at menopause. Maturitas 2006;54:27-38.
7. van Asselt KM, Kok HS, van Der Schouw YT, et al. Current
smoking atmenopause rather than duration determines the onset of
natural meno-
pause. Epidemiology 2004;15:634-639.
8. Gold EB, Colvin A, Avis N, et al. Longitudinal analysis of
the associationbetween vasomotor symptoms and race/ethnicity across
the menopausaltransition: Study of Womens Health Across the Nation.
Am J Public
Health 2006;96:1226-1235.9. den Tonkelaar I, te Velde ER, Looman
CW. Menstrual cycle length
preceding menopause in relation to age at menopause. Maturitas
1998;29:115-123.
10. Gold EB, Block G, Crawford S, et al. Lifestyle and
demographic fac-tors in relation to vasomotor symptoms: baseline
results from the Studyof Womens Health Across the Nation. Am J
Epidemiol 2004;159:1189-1199.
120 Menopause, Vol. 19, No. 2, 2012 * 2012 The North American
Menopause Society
EDITORIAL
Copyright 2012 The North American Menopause Society.
Unauthorized reproduction of this article is prohibited.
