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Department of Pediatric Endocrinology and Institut National de la Santé et de la Recherche Médicale U561 (J.-C.C., J.-L.C.) and Department of Biostatistics (C.E., E.E., J.C.), Groupe Hospitalier Cochin-Saint Vincent de Paul and Université Paris V, 75014 Paris, France; Department of Pediatric Endocrinology (M.T.), Hôpital des Enfants, 31059 Toulouse, France; Department of Pediatric Endocrinology (J.L.), Hôpital Robert Debré, 75935 Paris, France; Department of Pediatric Endocrinology (S.C.), Hôpital Armand Trousseau, 75571 Paris, France; Department of Pediatric Endocrinology (M.N.), Hôpital Debrousse, 69322 Lyon, France; and Department of Pediatric Endocrinology (R.B.), Hôpital de Bicêtre, 94275 Le Kremlin Bicêtre, France
Address all correspondence and requests for reprints to: Professor Jean-Claude Carel, Pediatric Endocrinology, Hôpital Robert Debré, 48, boulevard Sérurier, 75935 Paris Cedex 19, France. E-mail: carel{at}paris5.inserm.fr.
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Abstract |
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Objective: The objective of the study was to identify the determinants of self-esteem, social adjustment, and initiation of sex life in patients with Turner syndrome, particularly those related to pubertal management.
Design: This was a prospective evaluation, the StaTur study.
Setting: The study was conducted with a population-based registry of GH-treated patients.
Participants: Participants included 566 young adult women with Turner syndrome, aged 22.6 ± 2.6 yr (range, 18.3–31.2).
Main Outcome Measures: Measures used in the study were Coopersmith’s Self-Esteem Inventory, Social Adjustment Scale Self-Report, questions on sexual experience, and extensive data on pediatric management.
Results: Low self-esteem was associated with otological involvement and limited sexual experience. Low social adjustment was associated with lower paternal socioeconomic class and an absence of sexual experience. Late age at first kiss or date was associated with cardiac involvement and a lack of spontaneous pubertal development. Age at first sexual intercourse was related to age at puberty and paternal socioeconomic class. Delayed induction of puberty had a long-lasting effect on sex life. Height and height gain due to GH treatment had no effect on outcomes.
Conclusions: Puberty should be induced at a physiologically appropriate age in patients with Turner syndrome to optimize self-esteem, social adjustment, and initiation of the patient’s sex life. Therapeutic interventions altering normal pubertal development in other groups of patients should be reconsidered in light of these findings.
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Introduction |
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As for all chronic diseases of childhood, the medical treatment of Turner syndrome should aim to reduce the impact of this condition on psychosocial functioning, in both childhood and adulthood. However, the impact of management on psychosocial outcomes has not been systematically evaluated for Turner syndrome. In a previous study, we observed that health-related quality of life was similar in adult women with Turner syndrome treated with GH in childhood and the general population (11). We identified several components of the disease or consequences of medical management as factors associated with low health-related quality of life scores: cardiac and otological involvement, induction of puberty after the age of 15 yr, and higher expectations from GH treatment. In contrast, height or height gain from treatment had no influence (11). Other aspects of psychosocial functioning, such as self-esteem and social adjustment, have not been systematically evaluated in patients with Turner syndrome (12, 13, 14, 15). It is therefore important to analyze the influence of management options in childhood on these dimensions to help pediatricians make the best choices concerning the management of their patients.
The factors determining the onset of sexuality in humans are poorly characterized, and attention has mostly focused on behavioral, environmental, and psychosocial determinants (16). The timing of puberty affects the onset of sexuality in the general population (16, 17, 18). Several medical interventions affect the timing of puberty, but their effects on sexual behavior have not been studied (19, 20). Estrogen replacement in hypogonadal girls has a modest short-term effect on sexual behavior (21). Therefore, Turner syndrome, in which puberty is medically induced in most cases, provides a model to investigate the influence of the timing of puberty on the onset of sexuality.
In this study, we evaluated self-esteem, social adjustment, and sexuality, together with their determinants, in a population-based cohort of Turner syndrome patients treated with GH in France.
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Patients and Methods |
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Data collected
Data relating to features associated with Turner syndrome, growth, and treatments were collected throughout childhood and adolescence (9, 22). In 2001, a postal questionnaire was sent to all patients older than 18 yr on March 31, 2001. This survey included the Coopersmith’s Self-Esteem Inventory (SEI) (23) and the Social Adjustment Scale Self-Report (SAS-SR) (24) in addition to the quality of life questionnaire Short Form 36 of the Medical Outcome Study and the General Health Questionnaire 12 (GHQ-12), a measure of psychological distress (11, 25). It also dealt with demographic characteristics, current health status (morbidity, medication), sexual experience, and expectations from GH treatment. The SEI contains 58 trait-descriptive sentences to which subjects respond by indicating whether the sentences describe them. Scoring is based on a 26-item general subscale and on three 8-item subscales evaluating self-esteem in the social, family, and working areas. The total SEI score is the sum of the four subscales and ranges between 0 and 50. Higher scores indicate higher self-esteem. The SAS-SR questionnaire consists of 54 questions measuring instrumental and communicative role performance over the past 2 wk. It includes questions on work, social and leisure activities, relationships with family, marital partner, children, and perception of economic functioning. Each item is scored on a 5-point scale with higher scores indicating lower social adjustment.
Sexual experience was assessed by means of several questions, asking whether the young women had experienced kissing or dating and had had sexual intercourse (yes/no and age at the first time), from which we constructed two categorical variables. The first, called lifetime sexual experience, classified women as having: 1) no experience of kissing or dating; 2) kissing or dating experience but no experience of intercourse; 3) experience of sexual intercourse but no experience of living with a male partner; or 4) experience of sexual intercourse and currently living with a male partner. The second variable, sexual intercourse experience at the age of 20 yr, took into account the age of participants (with its obvious effect on sexual experience). Because normative national data indicate that 85% of women have experienced sexual intercourse by the age of 20 yr (26), we divided participants into three categories: 1) those who had had sexual intercourse before the age of 20 yr; 2) those over the age of 20 yr who had not had sexual intercourse before the age of 20 yr; and 3) women under the age of 20 yr with no experience of sexual intercourse, for whom no conclusion can be drawn. To evaluate the potential influence of the center at which patients had been followed up, we categorized them according to their size (large, n = 6, 188 patients; medium, n = 12, 181 patients; and small, n = 94, 197 patients). Body mass index (BMI) at the time of the questionnaire or adult height measurement was categorized in three tertiles (<20.5, 20.5–25, > 25 kg/m2) and expressed in SD score (SDS) using national normative data (27).
Statistical analysis
We quantified the relationships between subscores for the SEI and SAS-SR questionnaires, clinical and demographic characteristics, and sexual experience by means of univariate linear regression. Variables identified as significant in this univariate analysis were then included in a multiple regression model with a backward selection procedure (28).
Sexuality was analyzed by means of survival analysis, using first kiss or date or first sexual intercourse as the event considered. Given that events had not occurred in all women, we used age at time of the survey as censored time for these observations. Survival curves were derived from Kaplan-Meier estimates (29). Multivariate analyses used the Cox proportional hazards regression model (30), with a backward stepwise selection procedure. We defined P < 0.05 as statistically significant. Calculations were performed with SAS software (SAS Institute Inc., Cary, NC).
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Results |
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The flow chart describing enrollment of patients is presented in Fig. 1
. As described previously, participants (n = 566) and nonparticipants (n = 325) were similar in all characteristics except for adult height, participants being a mean of 2.7 cm taller than nonparticipants (11). Details on GH treatments and height outcomes have also been described earlier (9, 11). Medical and demographic characteristics and scores for the SEI and SAS-SR subscales are presented in Table 1. Women with Turner syndrome had low SEI scores, particularly for the general and social scales. Pubertal onset was defined as the time of spontaneous breast development or initiation of sex steroid treatment. Pubertal onset was medically induced in 405 patients at 14.9 ± 1.0 yr and spontaneous in 127 (missing data in 34). Of these 127 patients, 61 required sex steroids later, for pubertal development to complete. The mean BMI was 23.5 ± 4.3 kg/m2 or 1.0 ± 1.6 SD score.
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Five of the 38 variables tested were retained in the multivariate models (Table 2). Women with a high GHQ-12 score had low self-esteem, as estimated from all SEI components. Otological abnormalities were associated with low self-esteem in all but one dimension (work). Lifetime sexual experience was associated with the overall SEI scale and two of the four SEI subscales, with scores increasing with sexual experience. Earlier menarche was associated with lower self-esteem for the work dimension only, but age at onset of puberty (B2 stage) was not a predictor of SEI scores. Patients in the highest BMI tertile group had a lower general SEI score, compared with those of the middle BMI tertile group. Several variables were not associated with SEI scores. These variables included karyotype, participant’s professional situation, age at which the questionnaire was completed, height or parameters associated with GH treatment, genital malformations in patients with a 45,X/46,XY karyotype, size of the center, type of estrogen used, and delay to progestin treatment.
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Eight of the 38 potentially explanatory variables tested were retained in the multivariate models (Table 3). As expected, socioeconomic variables influenced social adjustment. Older participants had lower scores on the family scale. Categorical GHQ-12 score was correlated with all dimensions of social adjustment. Otological involvement had a minor effect. Lifetime sexual experience was associated with overall and social-leisure SAS-SR scale scores. In contrast to what was observed with the SEI scale, increasing sexual experience had no effect, suggesting an all-or-nothing effect of kissing or dating. Interestingly, women over the age of 20 yr at the time of the survey who had never had sexual intercourse or who had begun their sex lives late had higher scores on the work scale. Several variables were not associated with SAS-SR scores. These variables included adult height or estimated height gain, dysmorphic features, age at menarche, karyotype, cardiac involvement, genital malformations, size of the center, type of estrogen used, and delay to progestin treatment.
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Because sexuality was found an important determinant of self-esteem and social adjustment, we constructed Kaplan-Meier curves for the occurrence milestones in the development of sexuality (Figs. 2 and 3). In univariate analysis, age at first kiss or date was associated with age at the onset of puberty, induced vs. than spontaneous puberty, and ocular or cardiac involvement. In the final multivariate Cox model, induced (as opposed to spontaneous) puberty [hazard ratio (HR) 0.68 (95% confidence interval [CI] 0.50–0.93)], and cardiac involvement [HR 0.57 (95% CI 0.39–0.83)] were associated with age at first kiss or date. Age at first kiss or date was not associated with paternal socioeconomic class, dysmorphic features, adult height, or BMI.
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Discussion |
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Self-esteem was found to be low in several clinic- or support group-based samples of patients with Turner syndrome (31, 32). However, these studies were not population based, included patients from a wide range of age groups without taking age into account, and did not analyze factors associated with self-esteem and those related to pediatric care in particular. Ross et al. (32) suggested that the initiation of estrogen therapy was directly associated with an increase in self-esteem in 16-yr-old adolescents with Turner syndrome. Participants in our study were a mean of 6 yr older than the patients in Ross’s study. This may account for our finding no effect of age at the onset of puberty on self-esteem. We demonstrated that otological involvement was a major, unrecognized factor affecting self-esteem, suggesting that ear infections during childhood should be aggressively managed. The other main factor associated with self-esteem was sexual experience, which increased self-esteem. Overweight was associated with lower self-esteem as also reported in the non-Turner population (33). The strong association between GHQ-12 scores and self-esteem illustrate the fact that psychological distress and self-esteem are strongly interrelated. Inclusion of GHQ-12 scores in the explanatory models of self-esteem determinants allowed us to adjust for the level of psychological distress and decrease the risk of false-positive relationship in the multivariate analysis.
Previous clinic-based studies based on small samples have reported that Turner syndrome patients have a limited social life, with satisfactory adjustment to this situation. A high proportion of older individuals with Turner syndrome are reported to hold university degrees and be employed below their academic level (2, 3). We found that sexual experience affected social adjustment, but, in contrast to what was observed for self-esteem, kissing or dating experience had an all-or-nothing effect. Sexual experience before the age of 20 yr was negatively associated with social adjustment at work, even after adjustment for educational level. Similarly to self-esteem, inclusion of the GHQ-12 score in the models allowed to adjust for the level of psychological distress.
Our findings concerning the effect of sexual experience on psychosocial adaptation led us to investigate the factors associated with the initiation of sexual activity. Individuals with Turner syndrome are known to have their first sexual experience later, to be less likely to establish a steady relationship with a partner, and to be less sexually active than women from the general population (reviewed in Ref. 31). One study, including 80 women with Turner syndrome and a mean age of 34 yr, reported that 55% of these women had experience of sexual intercourse, with a mean age at first intercourse of 23 yr (34). In our study, 30% of the participants had had sexual intercourse by the age of 20 yr vs. 85% of women of the general population in France at the same age (26). Cardiac involvement was associated with dating beginning later, as would be expected given the severe adolescent morbidity associated with cardiac involvement. Age at the onset of puberty and type of puberty (spontaneous vs. induced), two closely related variables (9), were associated with age at first kiss or date. Differences were primarily associated with sustained spontaneous ovarian activity and persisted well after the age of 18 yr, when all participants had been exposed to estrogens. Androgen levels are reportedly low in adult women with Turner syndrome (35), and androgens play a role in female libido (36). It would therefore be of interest to evaluate the possible effects of androgen substitution on the initiation of sexual activity and psychosocial components in adolescents with Turner syndrome.
Daughters of manual workers tended to be older than daughters of non-manual workers at the time of first sexual intercourse, whereas in the general population, women from families with a low socioeconomic status tend to have sexual intercourse earlier (16, 17, 37, 38). This suggests that in patients from families with a higher socioeconomic status, the influence of Turner syndrome on relationships with the opposite sex is somewhat limited by coping strategies. Therefore, psychological counseling should particularly focus on women from lower socioeconomic status families. Age at puberty affected age at first sexual intercourse, and this effect persisted at least until the age of 25 yr when pubertal development had been underway for at least 7 yr in all girls. It is not possible to distinguish between psychosocial (i.e. having an age-appropriate physical development and therefore a better interaction with peers) and biological effects (i.e. a direct effect of sex steroids on the brain) based on our data. Nevertheless, our findings suggest that there may be a time window during which sex steroids must act on the brain at puberty to facilitate sexual behavior (39). Indeed, most studies in animal models (for male animals in most cases) have suggested that there is such a time window and that the consequences for sexual behavior of a lack of gonadal hormones during adolescence are irreversible (40).
Height and dysmorphic features were not associated with self-esteem and social adjustment, consistent with our results on health-related quality of life and calling into question the value of GH treatment (8). Furthermore, the lack of effect of height and dysmorphic features on sexual experience should help patients and health care providers to fight existing prejudices.
Several methodological aspects merit consideration. First, there may be differences regarding the studied outcomes between the patients who did not participate in the study (31%) and those who did. Nevertheless, we obtained a response rate of 69%, which is within acceptable standards for an unsolicited nominative questionnaire. Second, self-esteem and social adjustment measures might have been too crude to evidence small differences. However, the validity and reliability of the SAS-SR and SEI questionnaires have been well established (23, 24), and these instruments have largely been used in nonpatient populations and in diverse psychiatric samples (41, 42) in both English and French (43, 44). Third, our study included only young adult patients with Turner syndrome who were living in France and had been treated with GH. Some conclusions may thus not be applicable to non-GH-treated patients or in different cultural contexts. Last, some of the observations regarding the influence of sexual life on psychosocial adjustment are probably not specific to Turner syndrome and should be evaluated in other patient and nonpatient groups.
The validity of Turner syndrome as a model for studying the influence of the timing of puberty on the initiation of sexual activity and its psychosocial consequences could be questioned. However, our findings call into question several practices in which pubertal timing is manipulated, generally as a means of controlling height. High-dose estrogen treatment is used to reduce height and GnRH agonists are used to increase it (19, 20, 22). Our data suggest that the long-term consequences of these interventions may extend well beyond the intended effect, calling into question the value of their continued use.
We conclude that puberty should be induced at a physiologically appropriate age in patients with Turner syndrome to optimize self-esteem, social adjustment, and the initiation of sexual activity. Psychological support and counseling should be offered to patients, focusing particularly on those from families with a low socioeconomic status. Our findings show that the long-term analysis of carefully followed cohorts of patients with chronic childhood diseases can bring to light unexpected observations that might improve pediatric care. They also call into question the use of drugs affecting the timing of puberty in patients with spontaneous puberty that would otherwise occur at a normal age.
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Acknowledgments |
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The following clinicians were involved in the follow-up of a significant number of children in the study: Pascal Barat, Sabine Baron, Pascale Berlier, Philippe Bernard, Anne-Marie Bertrand, Hélène Bony-Trifunovic, Michel Bost, Bernard Boudailliez, Maryvonne Bouchard, Jean Caron, Jean-Pierre Charvet, Pierre Chatelain, Maurice Chupin, Michel Colle, Jean-Benoît Cotton, Paul Czernichow, Albert David, Michel David, Marc De Kerdanet, Francois Despert, Pierre Doyard, Christine Fedou, Anne Fjellestad-Paulsen, Patrick Garandeau, Philippe Garnier, Frédéric Huet, Jean-Claude Job, Michel Lecornu, Bruno Leheup, Anne Lienhardt, Jean-Marie Limal, Guy-André Loeuille, Eric Mallet, Georges Malpuech, Roger Mariani, Chantal Metz, Catherine Naud-Saudreau, Jean-Louis Nivelon, Sylvie Nivot, Christian Pauwels, Marc Pétrus, Catherine Pienkowski, Olivier Puel, Odile Richard, Pierre Rochiccioli, Gilbert Simonin, Sylvie Soskin, Véronique Sulmont, Charles Sultan, E. Thibaud, Jean-Edmond Toublanc, Kathy Wagner, Jacques Weill, and Catherine Wémeau.
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Footnotes |
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Conflicts of interest with several GH manufacturers: J.-C.C., M.T., J.L., S.C., M.N., R.B., and J.-L.C. have been investigators of several clinical trials of GH, have received fees for speaking at meetings and symposia, and have been invited to national and international meetings. C.E., E.E., and J.C. have no conflict of interest.
First Published Online May 23, 2006
Abbreviations: BMI, Body mass index; CI, confidence interval; GHQ-12, General Health Questionnaire 12; HR, hazard ratio; SAS-SR, Social Adjustment Scale Self-Report; SDS, SD score; SEI, Self-Esteem Inventory.
Received December 7, 2005.
Accepted May 15, 2006.
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This article has been cited by other articles:
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  C. A. Bondy and for The Turner Syndrome Consensus Study Group Care of Girls and Women with Turner Syndrome: A Guideline of the Turner Syndrome Study Group J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 10 - 25. [Abstract] [Full Text] [PDF]
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, Proportion of women without experience of sexual intercourse at the age of 20 yr in the general population in France (