scientific interest may be partly attributable to the
previous consensus that the female orgasm has no
clear role in reproduction. This view was challengedby research showing that the orgasm helped facilitate
sperm retention (Further evidence for the orgasm’s reproductive role
comes from studies linking it with the menstrual cycle(
More recently, this was corroborated in other studiesshowing that desire for pregnancy subconsciously
predicted timing of the female orgasm to be just afterthat of the male Studies such as
these are obviously difficult to conduct, and there is
still a lack of agreement among experts about the role
1Twin Research and Genetic Epidemiology Unit, St Thomas’ Hospital,
While differences in sexual function between
2Primary Care Sciences Research Centre, Keele University,
women were known to exist, these have been largely
attributed to cultural, religious and psychological
*Author for correspondence (tim.spector@kcl.ac.uk)
factors. No study has explored family history or gene-
Orgasmic dysfunction in females is commonly
tic factors—which might indicate or refute a biological
reported in the general population with little
or evolutionary basis for the variation. We therefore
consensus on its aetiology. We performed a
performed a classical twin study comparing the simi-
classical twin study to explore whether there
larities in identical and non-identical twins to explore
were observable genetic influences on femaleorgasmic dysfunction. Adult females from the
whether there were observable genetic influences on
TwinsUK register were sent a confidential survey
variation in female orgasmic function.
including questions on sexual problems. Com-plete responses to the questions on orgasmicdysfunction were obtained from 4037 women
consisting of 683 monozygotic and 714 dizygotic
Subjects for this study were monozygotic (MZ) and dizygotic (DZ)
pairs of female twins aged between 19 and 83
twins enlisted from the TwinsUK registry—the largest adult twin
years. One in three women (32%) reported never
or infrequently achieving orgasm during inter-
population has been involved in a wide range of studies on commontraits and diseases () ranging from catar-
course, with a corresponding figure of 21%
acts and blood clotting to musical ability (
during masturbation. A significant genetic influ-
ence was seen with an estimated heritability for
this registry have been shown to be comparable to the age-matched
difficulty reaching orgasm during intercourse of
general population for a broad variety of medical and behavioural
34% (95% confidence interval 27–40%) and 45%
traits After obtaining ethical approval from
(95% confidence interval 38–52%) for orgasm
the St Thomas’ Hospital ethics committee, a postal self-completionquestionnaire was sent to 3654 pairs of female twins aged between
during masturbation. These results show that
19 and 83 years including questions relating to sexual behaviour.
the wide variation in orgasmic dysfunction in
Complete confidentiality was assured and the twins were unaware
females has a genetic basis and cannot be
of any specific hypotheses. Zygosity was established by using
attributed solely to cultural influences. These
standardized questions that have over 95% accuracy
results should stimulate further research into
and further confirmed in 54% of the pairs by multiplex
the biological and perhaps evolutionary pro-
Orgasmic dysfunction was defined primarily using two questions
cesses governing female sexual function.
on frequency of orgasm during intercourse and masturbation. The
Keywords: twin studies; sexual dysfunction;
questions were, ‘Overall, how frequently do you experience anorgasm during intercourse?’ and ‘Overall, how frequently do you
experience an orgasm during masturbation by yourself or apartner?’ Responses were on a seven-point scale labelled as in
An individual’s phenotype is the result of the effects of both
genotype and environment. To study the sources of individualdifferences (i.e. the variance) in a phenotype, genetically related
Until recently, little research has explored female
subjects are required, and twins are ideal. MZ twin pairs share all
of their genes and DZ twin pairs share, on average, 50% of their
commonly report sexual dysfunction. For example,
segregating genes. Assuming that both types of twins share equallysimilar family environments, one can assert that any greater
over 50% of women in the UK report at least one
similarity between MZ twins than between DZ twins is a result of
sexual problem lasting a month or more during the
genetic influences. The similarities are estimated using the intra-
class correlation coefficient (ICC). Standard variance componentsmodel fitting was used to quantify the influences, and is based on
quarter have never or rarely achieved orgasm during
comparison of the covariance (or correlation) of a trait between
MZ and DZ twins ). This permits separation
is controversy over whether the problem has a real
of the observed phenotypic variance into additive and dominant
medical basis, or whether it has partly been created
genetic effects, and shared and unique environmental effects. Thesignificance of genetic and environmental factors as components of
by the media, pharmaceutical advertising and cultural
the observed variance is assessed by removing each sequentially
from the full model and testing the deterioration in fit of the
male sexual function is widely accepted (with a recent
various sub-models by hierarchic c2-tests. A heritability estimatecan be generated, defined as the proportion of total variation
increase following the release of drugs like Viagra),
that can be explained by genetic variance. Details of the
the female orgasm is less well studied. This lack of
analytical methods used are discussed in more detail in a paper by
Table 1. Details of twins studied by zygosity.
a p-values corrected for the relatedness of twins. b Range.
by either method (12% and 13%, respectively;
Table 2. Reported frequency (%) of experiencing orgasm
The ICCs for frequency of orgasm during inter-
course and masturbation were higher for MZ pairs
(31% and 39%, respectively) than for DZ pairs (10%
and 17%; pZ0.0001), suggesting a clear genetic
influence for both. Variance components modelling
revealed that the effects of the shared environment
and dominant genetic effects could be dropped from
the model without significant loss of fit, and provided
a quantitative estimate of additive genetic variance
(heritability) of 34% (95% confidence interval
27–40%) for orgasm during intercourse and 45%
a Excludes those not sexually active and missing responses.
(95% confidence interval 38–52%) for orgasm during
masturbation (see ). The remainder of thevariance was a result of random error and non-shared
. Preliminary analyses were carried out with
environmental factors. There was no significant effect
STATA software, while all genetic modelling was carried out with the
variance components program MX GUI v. 1.4.06 (
4. DISCUSSIONThis study shows that there is a significant genetic
component to variation in female orgasmic function
The questionnaire was returned by 4037 women,
that has not been reported previously. We believe our
comprising 1697 complete pairs (and 643 whose co-
results to be generalizable to singletons based on the
twin did not reply). A subset of 683 MZ pairs and
714 DZ twin pairs responded fully to the orgasmic
) and previous comparison studies of twins and
dysfunction questions, with no difference in respon-
dents between the groups. Details of the sample are
for complete pairs is comparable with the typical
response for medically oriented twin surveys, and
twin groups were similar in terms of divorce (26%
there was no evidence for an age bias. Further
and 25%, respectively), number of sexual partners
evidence for the generalizability of the findings comes
(means of between 4 and 5) and age (49 and 50
from the similarities in prevalence figures reported
years, respectively). The sample of respondents did
not appear to be biased towards younger subjects; the
average age of respondents was 50 years, the same as
variation in ability to orgasm can be explained by
for all the twins to whom the questionnaire was sent.
underlying genetic variation, with little or no role for
Of the sample, 98% sample reported being heterosex-
the shared environment (e.g. family environment,
ual and sexually active at some point.
religion, social class or early education). These herit-
The reported frequencies of experiencing orgasm
ability findings are in a similar range (35–60%) to
through intercourse and masturbation are shown in
other behavioural and complex traits such as
migraine, blood pressure, anxiety or depression and
unable to achieve orgasm during intercourse more
than a quarter of the time, and half of these women
). This is despite the greater difficulty in obtain-
(16% overall) never reached orgasm during inter-
ing information on aspects of sexual relationships
course. Conversely, 14% of women always experi-
compared with obtaining data, for example, on
enced orgasms during intercourse. More women were
able to orgasm during masturbation, with 34% always
). Our data lend support to the idea that
reaching orgasm. However, 21% were still unable to
variation in female orgasmic ability has a biological
orgasm more than a quarter of the time, two-thirds of
whom never achieved orgasm during masturbation.
As in all studies of this nature, there are limitations
There was no difference in the proportion of MZ and
to our study. There is potential for recall bias—but
DZ twins who never or infrequently reached orgasm
this would only have affected the results if there were
Table 3. Genetic modelling and estimates of heritabilities (given as additive genetic effects with 95% CI).
(A, additive genetic effects; C, common environmental effects; E, unique environmental effects; D, dominant genetic effects. Bold indicates best-fitting model and principal result.)
a systematic bias; for example, if MZ twins who
particularly its role in increasing fertility (
replied were more likely to show similar direction of
) and even in selecting sexually proficient mates
recall bias to their co-twin than DZ pairs. There was
no evidence of this, nor was there evidence of a
showing that genetic factors are the predominant
response difference in MZ or DZ twins, and the
measurable influence on female orgasmic function
subjects were not aware of any specific hypotheses.
will perhaps stimulate more research into understand-
Ideally, we would have used a more standardized
ing the underlying biological basis of the female
detailed questionnaire such as the GRISS
orgasm and sexual dysfunction. This will become
increasingly important, particularly as hormonal
intercourse frequency and sexual satisfaction. Use of
therapies for women (such as testosterone patches)
a questionnaire like this may have provided more
may be licensed shortly for a condition we know little
specific answers. However, such instruments and
investigations are lengthy, and inclusion may havereduced the response and hence the number of
The TwinsUK cohort collection is supported by the Well-
come Trust, the Chronic Disease Research Foundation and
errors resulting from the method of classification in
the ARC. We thank the twins for their invaluable help andAnn Johnson for help with the questionnaire and Dr Jannini
this study are unlikely to be different among MZ and
DZ twins. Such errors would result in an under-estimate of the genetic component, and the heritablecomponent may have been higher with more preciseinstruments.
Andrew, T., Hart, D. J., Snieder, H., de Lange, M.,
There is poor understanding of the physiology of
Spector, T. D. & MacGregor, A. J. 2001 Are twins andsingletons comparable? A study of disease-related and
sexual function and the microanatomy of female
lifestyle characteristics in adult women. Twin Res. 4,
sexual organs. Proposed biological influences include
anatomical variations such as the controversial pre-
Baker, R. R. & Bellis, M. A. 1995 Human sperm competition:
sence of Skene’s glands (G-spot) in the vaginal wall.
copulation, masturbation, and infidelity. London: Chapman
Recent work has found that nitric oxide type 5
phosphodiesterase pathways involved in male sexual
Berman, J. R., Berman, L. & Goldstein, I. 1999 Female
excitement are also present in women and may
sexual dysfunction: incidence, pathophysiology, evalu-
function similarly (D’Amati et al. ). This
ation, and treatment options. Urology 54, 385–391.
is partly supported by the partial success of clinical
Caruso, S., Intelisano, G., Lupo, L. & Agnello, C. 2001
Premenopausal women affected by sexual arousal dis-
trials in women of Viagra—a phosphodiesterase
order treated with sildenafil: a double-blind, cross-over,
placebo-controlled study. Br. J. Obstet. Gynaecol. 108,
important biological factors include androgen levels
or receptors, or natural variations in pleasure centres
D’Amati, G., di Gioia, C. R., Bologna, M., Giordano, D.,
in the brain, resulting from dopamine or other
Giorgi, M., Dolci, S. & Jannini, E. A. 2002 Type 5
phosphodiesterase expression in the human vagina.
All of these processes are probably mediated to some
extent by genetic variations. Other associated factors,
D’Amati, G., di Gioia, C. R., Proietti Pannunzi, L., Pistilli,
such as differences between individuals in anxiety and
D., Carosa, E. & Jannini, E. A. 2003 Functionalanatomy of the human vagina. J. Endocrinol. Invest. 26,
Davis, S. R. 2004 The use of testosterone after menopause.
contribute to the genetic component of orgasmic
De Lange, M., Snieder, H., Ariens, R. A., Spector, T. D. &
The physiological and evolutionary role of the
Grant, P. J. 2001 The genetics of haemostasis: a twin
female orgasm is highly speculative and controversial,
Drayna, D., Manichaikul, A., de Lange, M., Snieder, H. &
Morris, D. 1967 The naked ape. London: Cape.
Spector, T. 2001 Genetic correlates of musical pitch
Moynihan, R. 2003 The making of a disease: female sexual
recognition in humans. Science 291, 1969–1972.
Dunn, K. M., Croft, P. R. & Hackett, G. I. 1999
Neale, M. C. & Cardon, L. R. 1992 Methodology for genetic
Association of sexual problems with social, psychologi-
studies of twins and families. Dordrecht, The Netherlands:
cal, and physical problems in men and women: a cross
sectional population survey. J. Epidemiol. Community
Pfeiffer, E., Verwoerdt, A. & Davis, G. C. 1972 Sexual
Dunn, K. M., Jordan, K., Croft, P. R. & Assendelft, W. J. J.
2002 Systematic review of prevalence studies of common
Rijsdijk, F. V., Snieder, H., Ormel, J., Sham, P., Goldberg,
sexual problems. J. Sex Marital Ther. 28, 399–422.
D. P. & Spector, T. D. 2003 Genetic and environmental
Fox, C. A., Wolff, H. S. & Baker, J. A. 1970 Measurement
influences on psychological distress in the population:
general health questionnaire analyses in UK twins.
human coitus by radio-telemetry. J. Reprod. Physiol.
Rust, J. & Golombok, S. 1985 The Golombok–Rust
Hammond, C. J., Snieder, H., Spector, T. D. & Gilbert,
inventory of sexual satisfaction. Br. J. Clin. Psychol. 24,
C. E. 2000 Genetic and environmental factors in age-
related nuclear cataracts in monozygotic and dizygotic
Sarna, S., Kaprio, J., Sistonen, P. & Koskenvuo, M. 1978
twins. New Engl. J. Med. 342, 1786–1790.
Diagnosis of twin zygosity by mailed questionnaires.
Johnson, W. T. & DeLamater, J. D. 1976 Response effects
in sex surveys. Public Opin. Q. 40, 165–181.
Shifren, J. L., et al. 2000 Transdermal testosterone treat-
MacGregor, A. J., Snieder, H., Schork, N. J. & Spector,
ment in women with impaired sexual function after
T. D. 2000 Twins. Novel uses to study complex traits
oophorectomy. New Engl. J. Med. 343, 682–688.
and genetic diseases. Trends Genet. 16, 131–134.
Singh, D., Meyer, W., Zambarano, R. J. & Hurlbert, D. F.
Matteo, S. & Rissman, E. F. 1984 Increased sexual activity
1998 Frequency and timing of coital orgasm in women
during the midcycle portion of the human menstrual
desirous of becoming pregnant. Arch. Sex. Behav. 27,
Mercer, C. H., Fenton, K. A., Johnson, A. M., Wellings,
Spector, T. D. & MacGregor, A. J. 2002 The St Thomas’
K., Macdowall, W., McManus, S., Nanchahal, K. &
UK adult twin registry. Twin Res. 5, 440–443.
Erens, B. 2003 Sexual function problems and help
Walsh, K. E. & Berman, J. R. 2004 Sexual dysfunction in
seeking behaviour in Britain: national probability sample
the older woman: an overview of the current under-
standing and management. Drugs Aging 21, 655–675.
One of the primary roles of Emergency Medical Ser-vices is to provide emergency care for life-threatening medical events. This section reviews clinical and system considerations in the EMS care of these time-critical conditions. Altered Mental Status/Altered Level of Consciousness INTRODUCTION patient as possible from the scene. Because the patient often cannot provide an adequate history, fi
Relationship of Type II Diabetes and Metformin Use to Ovarian Cancer Progression, Survival, and Chemosensitivity Iris L. Romero, MD, MS, Anna McCormick, MD, DO, Kelsey A. McEwen, BS, SeoYoung Park, PhD,Theodore Karrison, PhD, S. Diane Yamada, MD, Silvana Pannain, MD, and Ernst Lengyel, MD, PhD OBJECTIVE: To estimate whether metformin use by and the diabetic patients who did not use metf