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Shyness, Social Anxiety, and Impaired Self-esteem in Turner Syndrome and Premature Ovarian Failure

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Peter J Schmidt
Peter J Schmidt
Peter J Schmidt
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Graca Cardoso at Universidade NOVA de Lisboa
Graca Cardoso
Judith L Ross at Thomas Jefferson University
Judith L Ross
Nazli Haq
Nazli Haq
Nazli Haq
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that is reduced with testosterone replacement.
7
Because both
Turner syndrome groups in this study had ovarian failure,
sex ster oids ar e not likely contributors to the present findings.
Limitations of this study include a relatively small sample
size. As an obser vational study, results could be due to un-
measured confounders. The cross-sectional design limits in-
ferences about causality. While interpretation of the P val-
ues should consider that there were 6 comparisons, the
parallel increases in plasma lipids and abdominal adiposity
are biologically consistent. Additional research is needed to
confirm these findings and to extend them to X chromo-
some effects in normal men and women.
However, these results suggest a role of X chromosome
gene dosage in metabolic regulation that could be ex-
plained by the imprinting (silencing) of maternally trans-
mitted X-linked genes that normally prevent visceral fat ac-
cumulation, or imprinting of paternally transmitted X-linked
genes that normally promote visceral fat accumulation. Iden-
tification of these putative imprinted X-linked genes and
elucidation of the epigenetic mechanisms involved in their
differential expression could have implications for cardio-
vascular health.
Phillip L. Van, MS
Vladimir K. Bakalov, MD
Developmental Endocrinology Branch
National Institute of Child Health and Human Development
National Institutes of Health
Bethesda, Md
Andrew R. Zinn, MD, PhD
McDermott Center for Human Growth and Development
University of Texas Southwestern Medical School
Dallas
Carolyn A. Bondy, MD
bondyc@mail.nih.gov
National Institute of Child Health and Human Development
National Institutes of Health
Bethesda
Author Contributions: Dr Bondy had full access to all of the data in the study and
takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Zinn, Bondy.
Acquisition of data: Van, Bakalov, Zinn, Bondy.
Analysis and interpretation of data: Van, Bakalov, Zinn, Bondy.
Drafting of the manuscript: Van, Zinn, Bondy.
Critical revision of the manuscript for important intellectual content:Van, Bakalov,
Zinn, Bondy.
Statistical analysis: Van, Bakalov, Bondy.
Obtained funding: Bondy.
Administrative, technical, or material support: Bondy.
Study supervision: Bondy.
Financial Disclosures: None reported.
Funding/Support: This research was supported by the Intramural Research Pro-
grams of the National Institute of Child Health and Human Development.
Role of the Sponsor: The sponsor had no role in the design and conduct of the
study; collection, management, analysis, and interpretation of the data; or prepa-
ration, review, and approval of the manuscript.
Acknowledgment: We thank the study participants; Eileen Lange, RN, and the staff
of the NIH clinical research center for their care of our patients; and Purita Ramos,
BS, for assistance with X chromosome genotyping. Ms Ramos is supported by NIH
grant NS35554.
1. Carr MC, Hokanson JE, Zambon A, et al. The contribution of intra-abdominal
fat to gender differences in hepatic lipase activity and low/high density lipopro-
tein heterogeneity. J Clin Endocrinol Metab. 2001;86:2831-2837.
2. Cooley M, Bakalov V, Bondy CA. Lipid profiles in women with 45,X vs 46,XX
primary ovarian failure. JAMA. 2003;290:2127-2128.
3. Wilkins JF. Genomic imprinting and methylation: epigenetic canalization and
conflict. Trends Genet. 2005;21:356-365.
4. Skuse DH, James RS, Bishop DV, et al. Evidence from Turner’s syndrome of an
imprinted X-linked locus affecting cognitive function. Nature. 1997;387:705-708.
5. James RS, Coppin B, Dalton P, et al. A study of females with deletions of the
short arm of the X chromosome. Hum Genet. 1998;102:507-516.
6. NIH Clinical Center Test Guide. Available at: http://cclnprod.cc.nih.gov/dlm
/testguide.nsf. Accessed February 11, 2006.
7. Wu FCW, von Eckardstein A. Androgens and coronary artery disease. Endocr
Rev. 2003;24:183-217.
Shyness, Social Anxiety, and Impaired
Self-esteem in Turner Syndrome
and Premature Ovarian Failure
To the Editor: Shyness and social anxiety are reported in
women with Turner syndrome (TS).
1
Possible contribu-
tors include physical stigmata, such as short stature and neck-
webbing, chromosomally-based deficits in social cogni-
tion, and premature ovarian failure with infertility. To
investigate the potential role of premature ovarian failure
and infertility, we compared measures of psychosocial dis-
tress in women with TS, women with spontaneous karyo-
typically normal premature ovarian failure (POF), and
healthy controls.
Methods. Participants in this institutional review board–
approved study were recruited through National Institutes
of Health (NIH) Web sites and newspapers and provided writ-
ten informed consent. Inclusion criteria for patients with
TS and POF are described elsewhere.
2
Daily hormone therapy
Table. X Chromosome Parental Origin and Metabolic Profile
Mean (SD)
P
Value*X
M
X
P
All patients, No. 62 27
Age, y 30.7 (10.9) 26.7 (11.6) .11
BMI 27.6 (6.3) 25.2 (6.3) .15
Fasting glucose, mg/dL 83 (10) 82 (7) .68
Fasting insulin, µU/mL 8.2 (7.0) 8.1 (4.6) .95
Triglycerides, mg/dL 131 (62) 100 (50) .01
Total cholesterol, mg/dL 208 (40) 189 (43) .02
LDL-C, mg/dL 137 (41) 113 (44) .004
HDL-C, mg/dL 58 (13) 61 (17) .17
Patients aged ⱖ18 y, No. 40 16
Age, y 34.1 (9.3) 32.2 (10.1) .51
BMI 28.6 (7.8) 27.4 (7.1) .59
Total body fat by DXA, % 37.1 (7.6) 36.3 (8.1) .27
Total abdominal fat, mL 78.3 (49.0) 57.7 (36.0) .005
Visceral abdominal fat, mL 24.8 (19.4) 13.9 (8.0) ⬍.001
Abbreviations: BMI, body mass index, calculated as weight in kilograms divided by the
square of height in meters; DXA, dual-energy x-ray absorptiometry; HDL-C, high-
density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; X
M
, mater-
nally inherited X chromosome; X
P
, paternally inherited X chromosome.
SI conversions: To convert glucose to mmol/L, multiply by 0.0555; to convert triglycer-
ides to mmol/L, multiply by 0.0113; to convert total cholesterol, HDL-C, and LDL-C
to mmol/L, multiply by 0.0259.
*Group means were compared by 1-way analysis of variance/analysis of covariance fol-
lowed by Fisher protected least-significant-difference tests. Age and BMI were used
as covariates in comparing metabolic and adiposity measures. Two-sided P values
were calculated for age, BMI, fasting glucose, and fasting insulin; all other P values
are 1-sided.
LETTERS
1374 JAMA, March 22/29, 2006—Vol 295, No. 12 (Reprinted) ©2006 American Medical Association. All rights reserved.
at National Institute of Hlth, on March 21, 2006 www.jama.comDownloaded from
was taken by 99% of the women with TS and 90% with POF
but was discontinued 2 weeks before evaluation.
Control participants were recruited from the local com-
munity and were paid a small stipend. They were required
to have regular menstrual cycles, take no medications, and
have no current or past medical or psychiatric conditions.
Control participants were interviewed during the follicular
phase of their menstrual cycle.
Testing was performed in the NIH Clinical Research Cen-
ter between January 2001 and January 2004. Participants
completed 4 rating scales previously validated in commu-
nity populations: the shyness scale,
3,4
social anxiety scale,
5
Rosenberg’s self-esteem scale,
6
and the Center for Epide-
miologic Studies–Depression Scale.
7
From an initial sample
of 103 women with TS, 100 fully completed all the sur-
veys; and from an initial sample of 128 women with POF,
100 completed all surveys. Age and marital status did not
differ significantly between participants and nonparticipants.
Group means were compared using analysis of variance with
age and body mass index (calculated as weight in kilograms
divided by the square of height in meters) as covariates. Mul-
tiple linear regr ession was used to examine the effects of age,
years of education, years of hormone therapy (as a measure
of duration of ovarian failure), and marital status on scores.
For comparisons of rating scale scores between women with
TS and those with POF, sample sizes of 96 to 104 women per
group provided 90% power to detect a differ ence of 10% or
greater on any of the rating scales with ␣ =.05. Analyses ex-
cluding women with TS younger than 18 years showed simi-
lar results and are not reported. All analyses were performed
using Stat View 5.0.1 (SAS Institute Inc, Cary, NC).
Results. There were group differences in the percentage
of participants taking thyroid or antidepressant medica-
tion (T
ABLE 1). However, all women were euthyroid, and
these medications were continued during the study. More
women with POF were married, likely reflecting their ini-
tial presentation of infertility.
Turner syndrome and POF groups scored significantly
higher on the shyness scale, social anxiety scale, and the Cen-
ter for Epidemiologic Studies–Depression Scale, and lower
on the self-esteem scale compared with controls (T
ABLE 2).
However, there were no significant differences between the
TS and the POF groups for the scores on any of these scales.
Age, years of education, years of hormone therapy, and mari-
tal status did not contribute to score variations in TS or POF.
Comment. In this study population, 2 dissimilar groups
of women who had experienced premature ovarian failure
had similar psychosocial profiles, with increased shyness,
social anxiety, and depression, and decreased self-esteem com-
pared with women with healthy ovarian function. These re-
sults are not likely to be due to ovarian hormone defi-
ciency because the majority of women in both groups were
taking hormone therapy. Short-term cessation of hormone
therapy should not result in changes in these scales that mea-
sure chronic social distress. Although our results do not pro-
Table 1. Characteristics of Women With Turner Syndrome,
Karyotypically Normal Premature Ovarian Failure, and Healthy
Controls
Turner
Syndrome
(n = 100)
Premature
Ovarian Failure
(n = 100)
Healthy
Controls
(n = 35)
Age, mean (SD) [range], y 34.7 (11.6)
[16-61]
30.9 (5.7)
[19-42]
35.8 (9.6)
[19-50]
Ethnicity, No. (%)*
White 91 (91) 85 (85) 23 (66)
Black 1 (1) 8 (8) 9 (26)
Asian 3 (3) 3 (3) 2 (6)
Hispanic 5 (5) 4 (4) 1 (2)
BMI, mean (SD) 27.6 (6.5) 23.6 (4.4) 23.2 (4.0)
Height, mean (SD), cm 146.2 (10.0) 165.0 (7.5) 160.8 (6.2)
Hormone therapy duration,
mean (SD), y
14.6 (10.7) 4.9 (4.4) NA
Taking thyroid medication, No. (%)† 33 (33) 7 (7) 0
Taking antidepressant medication,
No. (%)†
14 (14) 13 (13) 0
Education, mean (SD), y 16.3 (2.1) 17.0 (2.8) 17.0 (2.6)
Currently married, No. (%) 31 (31) 85 (85) 15 (43)
Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by the square
of height in meters); NA, not applicable.
*Race/ethnicity based on patient self-identification using National Institutes of Health cat-
egories.
†All women were euthyroid. Antidepressant and thyroid hormone medications were con-
tinued during this study.
Table 2. Results of Psychological Tests
Mean Score (95% CI)
P Value*
TS POF Healthy Controls
TS vs
Healthy Controls
POF vs
Healthy Controls TS vs POF
Shyness scale† 34.4 (32.3-36.6) 31.9 (29.3-33.3) 23.8 (20.8-26.8) ⬍.001 ⬍.001 .11
Social anxiety scale‡ 23.0 (20.3-25.8) 21.9 (18.8-23.7) 10.8 (8.7-13.5) ⬍.001 ⬍.001 .58
Rosenberg’s self-esteem scale§ 31.6 (30.5-32.6) 32.5 (31.7-33.7) 36.4 (35.0-37.6) ⬍.001 ⬍.001 .20
Center for Epidemiologic
Studies–Depression Scale 㛳
10.1 (8.6-11.9) 11.9 (9.7-13.9) 3.3 (1.8-4.3) ⬍.001 ⬍.001 .13
Abbreviations: CI, confidence interval; POF, premature ovarian failure; TS, Turner syndrome.
*Comparison of group means by analysis of variance with age and body mass index as covariates.
†Scale ranges from 14 to 70, with scores of higher than 35 indicative of clinically significant shyness.
3,4
‡Scale ranges from 0 to 80, with higher scores indicating more severe social anxiety.
5
§Scale ranges from 10 to 40, with higher scores indicating greater self-esteem.
6
㛳Scale ranges from 0 to 60, with scores of 16 or higher consistent with major depression.
LETTERS
©2006 American Medical Association. All rights reserved. (Reprinted) JAMA, March 22/29, 2006—Vol 295, No. 12 1375
at National Institute of Hlth, on March 21, 2006 www.jama.comDownloaded from
vide an explanation for this symptom profile, uncontrolled
studies
8
suggest infertility as a factor.
Study limitations include the use of self-selected groups
that were primarily white, relatively well-educated, and took
the initiative to participate in NIH protocols; as such, they
may not be representative of other women with premature
ovarian failure. Control participants were screened for the
absence of psychiatric illness so their rating scale scores could
have been biased toward less distress than those from a gen-
eral population. As a cross-sectional study, conclusions about
causality cannot be made and, as an observational study, as-
sociations could be due to unmeasured confounding. To con-
firm these findings, it is important to study other groups,
such as young women with ovarian failure secondary to can-
cer or cancer therapy. Nevertheless, these results suggest that
clinicians should consider these psychosocial issues in ad-
dition to the medical consequences for patients with pre-
mature ovarian failure.
Peter J. Schmidt, MD
peterschmidt@mail.nih.gov
Graca M. P. Cardoso, MD
Behavioral Endocrinology Branch
National Institute of Mental Health
National Institutes of Health
Bethesda, Md
Judith L. Ross, MD
Department of Pediatrics
Thomas Jefferson University
Philadelphia, Pa
Nazli Haq, MA
David R. Rubinow, MD
Behavioral Endocrinology Branch
National Institute of Mental Health
Carolyn A. Bondy, MD
Developmental Endocrinology Branch
National Institute of Child Health and Human Development
National Institutes of Health
Bethesda, Md
Author Contributions: Dr Schmidt had full access to all the data in the study and takes
responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Schmidt, Ross, Rubinow, Bondy.
Acquisition of data: Schmidt, Cardoso, Ross, Haq, Bondy.
Analysis and interpretation of data: Schmidt, Cardoso, Ross, Rubinow, Bondy.
Drafting of the manuscript: Schmidt, Cardoso, Bondy.
Critical revision of the manuscript for important intellectual content: Schmidt,
Haq, Rubinow.
Statistical analysis: Schmidt, Cardoso, Ross, Haq, Rubinow, Bondy.
Obtained funding: Schmidt.
Administrative, technical, or material support: Schmidt.
Study supervision: Schmidt.
Financial Disclosures: None reported.
Funding/Support: This work was supported by the Intramural Research Programs
of the National Institute of Mental Health and National Institute of Child Health
and Human Development and supported in part by grant NS42777 from the Na-
tional Institutes of Health (Dr Ross).
Role of the Sponsors: The sponsors had no role in the design and conduct of the
study; collection, management, analysis, and interpretation of the data; and the
preparation, review, or approval of the manuscript.
Acknowledgment: We thank the study participants and are grateful to Eileen Lange,
RN, CCRP, and Vien Vanderhoof, LNP, for recruiting and caring for our patients.
We also thank Lawrence Nelson, MD, for pioneering research on premature ovar-
ian failure and Vladimir K. Bakalov, MD, for informal uncompensated statistical
consultation.
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Endocrinol Metab. 2003;88:5717-5722.
3. Watson AK, Cheek JM. Shyness situations: perspectives of a diverse sample of
shy females. Psychol Rep. 1986;59:1040-1042.
4. Heiser NA, Turner SM, Beidel DC. Shyness: relationship to social phobia and
other psychiatric disorders. Behav Res Ther. 2003;41:209-221.
5. Mattick RP, Clarke JC. Development and validation of measures of social pho-
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6. Hensley WE, Roberts MK. Dimensions of Rosenburg’s self-esteem scale. Psy-
chol Rep. 1976;38:583-584.
7. Radloff L. The CES-D Scale: a self-report depression scale for research in the
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8. Greil AL. Infertility and psychological distress: a critical review of the literature.
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Depression Among Pregnant Rural South African
Women Undergoing HIV Testing
To the Editor: Rates of human immunodeficiency virus (HIV)
infection in southern Africa are high, with up to 45% of preg-
nant women being HIV-positive.
1
Depression is associated
with lowered adherence to antiretroviral medication
2
and
poor use of antenatal care.
3
It frequently persists into the
postnatal period, raising the risk of adverse child out-
comes.
3
Because little is known about the rates of depres-
sion among women undergoing HIV testing in prevention
of mother-to-child transmission programs (PMTCT), we un-
dertook this prevalence study. A secondary aim was assess-
ment of perceptions among these women about adverse con-
sequences of an HIV diagnosis, and whether these perceptions
were related to depression status.
Methods. This study was conducted in rural northern Kwa-
Zulu-Natal, South Africa, a region with a very high HIV preva-
lence.
1
A consecutive sample of women offered PMTCT dur-
ing routine antenatal care at 3 representative clinics
4
was
invited to participate. Women were eligible if this was their
first HIV test in the current pregnancy and they had not pre-
viously tested HIV-positive. Written informed consent was
obtained and approval was granted by the Ethics Review
Board of the University of KwaZulu-Natal and the Oxford
Tropical Research Ethics Committee. Enrollment was ob-
tained from 242 (82%) of the eligible women. Reasons for
nonparticipation included insufficient time, nonreturn af-
ter requesting opportunity to discuss with family, and un-
willingness to participate in research. Ethics boards did not
permit collection of any other comparison data from
nonparticipants.
Depressive symptoms wer e assessed with the Edinburgh
Postnatal Depression Scale (EPDS). It has specificity and
sensitivity greater than 76%,
5
has been validated antena-
tally and postnatally,
6
and has been validated in a black
South African population.
7
Depression was defined by a
score of 13 or above.
6
Any patient reporting recent
thoughts of self-harm was referred for intervention. A
9-item questionnaire scored in 3 domains (health care
access, financial resources, and social support) was used to
elicit women’s perceptions of the consequences of an HIV
LETTERS
1376 JAMA, March 22/29, 2006—Vol 295, No. 12 (Reprinted) ©2006 American Medical Association. All rights reserved.
at National Institute of Hlth, on March 21, 2006 www.jama.comDownloaded from
... Previous studies have also demonstrated that women with POI would suffer more frequent and severe symptoms of depression than age-matched women without POI. 7,17 Unlike women who do not suffer from POI, the symptoms of depression were not limited to the period of their transition through perimenopause in patients with POI. 18 Another key factor associated with the prevalence of depression is marital status, and some previous studies have repeatedly shown that people who are divorced, separated, single, and widowed have poorer mental health than married women. ...
... Loss of fertility is highly distressing and increases the risk of psychological problem, including anxiety, in women with POI/POF. 17,24 Women with both idiopathic and iatrogenic POI exhibited more severe anxiety than women without POI. 16,25 However, a recent study showed that the severity of anxiety among women with POI was not significantly different from age-matched women without POI. ...
... Many previous studies have reported greater levels of depression and lower levels of self-esteem in women with POI. 11,17,24,44,45 In line with these findings, our results confirmed supported that POI/POF could increase the risk of depression. The association between the POI/POF and depression is likely related to the loss of fertility potential and ovarian steroid deficiency. ...
Premature Ovarian Insufficiency Is Associated with Increased Risk of Depression, Anxiety, and Poor Life Quality: A Systematic Review and Meta-analysis
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Background Premature ovarian insufficiency (POI) seriously affects the reproductive health of women. Several studies have been conducted to show that POI appears to be associated with psychological and psychosocial problems, but whether POI increases the risk of mental health problems has not been identified. Therefore, this meta-analysis provides a preliminary systematic assessment of the studies published to date on the impact of POI on women’s mental health. Methods We implemented a systematic search for studies on this topic up to October 2022. Pooled odds ratios (ORs) and 95% confident intervals (CIs) of prevalence were used to assess the impacts of POI on various psychological factors, and the publication bias was assessed by Egger’s test. Results A total of 15 articles comprising 5820 participants were included in this meta-analysis. POI was found to be related to higher risk of 13 psychological and psychosocial problems identified and classified into 3 domains: depression (OR = 1.61; 95% CI: 1.11-2.33), anxiety (OR = 3.74; 95% CI: 1.78-7.87), and poor life quality (OR = 2.55, 95% CI: 1.63-3.97). Conclusion This meta-analysis reveals that women with POI have an increased risk of depression, anxiety, and poor life quality. The marital status of POI may be a possible influencing factor for depression, meaning that the unmarried status in POI is at high risk of psychological and psychosocial problems. We should pay attention to the mental health of women with POI who were unmarried.
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... Conversely, individuals with lower resilience may struggle to overcome negative emotions when under stress (Ong et al., 2006). Additionally, high-resilience individuals facing adversity or stressful events, such as quarantine measures implemented to prevent the spread of pandemics, tend to have a stronger positive social orientation and a more positive attitude towards negative events, which can reduce their negative emotions (Pinquart, 2009;Schmidt et al., 2006). These findings support the idea that individuals with higher psychological resilience experience lower levels of depression (Barzilay et al., 2020;Serrão et al., 2021). ...
Psychological resilience and depression among college students during the COVID-19 pandemic: The mediating role of self-forgiveness and the moderating role of isolation
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Previous research has consistently reported a negative association between psychological resilience and depression. However, the potential impact of other variables, such as self-forgiveness and isolation, on this relationship remains unexplored. The aim of this study was to investigate the mediating role of self-forgiveness and the moderating role of isolation in the association between psychological resilience and depression among college students in China. A total of 1,274 college students in China completed a screening questionnaire that included measures of psychological resilience, self-forgiveness, depression, and isolation. After excluding invalid data, 1,220 valid responses were used for the moderated mediation analysis. The results of the mediation analysis indicated that self-forgiveness had a significant mediating effect on the relationship between psychological resilience and depression (ES = − .40). Furthermore, the moderated mediation analysis revealed that isolation significantly moderated the first half of the mediating path and the direct path of the mediating model. These results provided a theoretical foundation for enhancing individual psychological resilience and self-forgiveness as coping mechanisms to manage depression in negative situations, as well as highlighting the negative impact of isolation on individual mental health. Moreover, the findings highlighted the importance of emphasizing the cultivation of psychological resilience and self-forgiveness as integral components of therapeutic programs to optimize their efficacy.
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... (Table S1) Impaired fertility represents the most distressing consequence of POI, imposing a significant psychological burden on young women. The presence of impaired fertility and the fear of premature aging are linked to a loss of emotional control, diminished self-esteem, social anxiety, and an increased incidence of depressive symptoms [85]. Currently, there are no clearly effective interventions to enhance residual ovarian function, with the primary approach being the use of donated eggs to improve the conception rate among women with POI (van Kasteren and Schoemaker 1999; [86]. ...
Premature ovarian insufficiency: a review on the role of tobacco smoke, its clinical harm, and treatment
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Premature ovarian insufficiency (POI) is a condition in which the quantity of follicles and the quality of oocytes gradually decrease. This results in an estrogen secretion disorder and abnormal follicle development, which can lead to related diseases, early onset of menopause, sexual dysfunction, and an increased risk of cardiovascular issues, osteoporosis, and depression, among others. This disease significantly impacts the physical and mental health and overall quality of life of affected women. Factors such as genetic abnormalities, oophorectomy, radiotherapy for malignancy, idiopathic conditions, and an unhealthy lifestyle, including smoking, can accelerate the depletion of the follicular pool and the onset of menopause. Extensive research has been conducted on the detrimental effects of tobacco smoke on the ovaries. This article aims to review the advancements in understanding the impact of tobacco smoke on POI, both in vivo and in vitro. Furthermore, we explore the potential adverse effects of common toxicants found in tobacco smoke, such as polycyclic aromatic hydrocarbons (PAHs), heavy metals like cadmium, alkaloids like nicotine and its major metabolite cotinine, benzo[a]pyrene, and aromatic amines. In addition to discussing the toxicants, this article also reviews the complications associated with POI and the current state of research and application of treatment methods. These findings will contribute to the development of more precise treatments for POI, offering theoretical support for enhancing the long-term quality of life for women affected by this condition.
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... Our findings showing a stable, overall effect of TS on the brain are consistent with previous studies documenting alterations in the amygdala, and gray matter of the pericalcarine, parietal and postcentral cortices of females with TS (Good et al., 2003;Kesler et al., 2004;Molko, 2004). Alterations in the frontal cortex and amygdala may be associated with the high prevalence of anxiety (McCauley et al., 1987;Schmidt et al., 2006) and social dysfunction in this population Lepage, Dunkin, et al., 2013;McCauley et al., 1987;Romans et al., 1998). Parietal and postcentral alterations, in turn, may be related to TS-associated deficits in visuospatial and sensory processing, respectively (Jajor et al., 2019;McCauley et al., 1987;Murphy et al., 1994). ...
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Turner syndrome (TS) is a common sex chromosome aneuploidy in females associated with various physical, cognitive, and socio-emotional phenotypes. However, few studies have examined TS-associated alterations in the development of cortical gray matter volume and the two components that comprise this measure-surface area and thickness. Moreover, the longitudinal direct (i.e., genetic) and indirect (i.e., hormonal) effects of X-monosomy on the brain are unclear. Brain structure was assessed in 61 girls with TS (11.3 ± 2.8 years) and 55 typically developing girls (10.8 ± 2.3 years) for up to 4 timepoints. Surface-based analyses of cortical gray matter volume, thickness, and surface area were conducted to examine the direct effects of X-monosomy present before pubertal onset and indirect hormonal effects of estrogen deficiency/X-monosomy emerging after pubertal onset. Longitudinal analyses revealed that, whereas typically developing girls exhibited normative declines in gray matter structure during adolescence, this pattern was reduced or inverted in TS. Further, girls with TS demonstrated smaller total surface area and larger average cortical thickness overall. Regionally, the TS group exhibited decreased volume and surface area in the pericalcarine, postcentral, and parietal regions relative to typically developing girls, as well as larger volume in the caudate, amygdala, and temporal lobe regions and increased thickness in parietal and temporal regions. Surface area alterations were predominant by age 8, while maturational differences in thickness emerged by age 10 or later. Taken together, these results suggest the involvement of both direct and indirect effects of X-chromosome haploinsufficiency on brain development in TS.
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... The prevalence of POI is 1-3% in women below 40 years of age and around 0.1% in women under 30 (2). This disorder affects women physically, psychologically, socially, and sexually and results in irregular menstruation, symptoms of premature menopause, infertility, osteoporosis, endocrine and cardiovascular diseases (3), anxie-ty, depression (4)(5)(6)(7), and impaired self-esteem (8)(9)(10). Although the final outcome of POI in women culminates in its adverse effects on general health, sexual and reproductive health, and consequently reduced quality of life (11)(12)(13), one of the worst adverse consequences is the threat to the female identity as a result of women perception and experience of altered womanhood after diagnosis of POI (14). ...
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Full-text available
  • Feb 2023
Background: Premature ovarian insufficiency (POI) occurs in women before the age of 40. Although the outcomes of POI in women include its adverse effects on general health, sexual-reproductive health, and finally reduced quality of life. One of the first adverse consequences is a threat to female identity of the patients. The purpose of the present study was to investigate the perception and experience of women with POI about female identity. Methods: In this qualitative study, interviews were conducted with 15 women having POI. Data included participants' recorded voices that were analyzed using conventional content analysis. Results: After content analysis of the interviews with a focus on the perception and experience of women with POI about female identity, four categories emerged; they included the failure in realization of motherhood dream, the importance of menstruation, construction of female identity, and attempts to normalize the situation. Conclusion: After analyzing the emerged categories obtained by interviewing with POI women, it seems that physicians need to pay special attention to the distortion of the female identity of these patients and educate the medical team about the importance of the effect of treatment on improving their emotional health.
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Clinical Practice Guidelines for the Care of Girls and Women with Turner Syndrome
Article
  • May 2024
Turner syndrome affects 50 per 100,000 females, affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and US culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: 1) diagnosis and genetics, 2) growth, 3) puberty and estrogen treatment, 4) cardiovascular health, 5) transition, 6) fertility assessment, monitoring, and counselling, 7) health surveillance for comorbidities throughout the lifespan, and 8) neurocognition and its implications for mental health and well-being. Each group produced proposals for the present guidelines, which were meticulously discussed by the entire group. Four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with systematic review of the literature. The guidelines project was initiated by the European Society for Endocrinology and the Pediatric Endocrine Society, in collaboration with members from the European Society for Pediatric Endocrinology, the European Society of Human Reproduction and Embryology, the European Reference Network on Rare Endocrine Conditions, the Society for Endocrinology, and the European Society of Cardiology, Japanese Society for Pediatric Endocrinology, Australia and New Zealand Society for Pediatric Endocrinology and Diabetes, Latin American Society for Pediatric Endocrinology, Arab Society for Pediatric Endocrinology and Diabetes, and the Asia Pacific Pediatric Endocrine Society. Advocacy groups appointed representatives for pre-meeting discussions and the consensus meeting.
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An extra X chromosome among adult women in the Million Veteran Program: A more benign perspective of trisomy X
Article
  • Mar 2024
  • AM J MED GENET C
Despite affecting in 1 in every 1000 females, remarkably little is known about trisomy X syndrome (47,XXX), especially among older adults who are undiagnosed. In this study, we aimed to determine the prevalence of 47,XXX among females enrolled in the Million Veterans Program (MVP; mean age 50.2 ± 13.6 years), and compare broad health outcomes between females with 47,XXX and 46,XX matched controls. We identified 61 females with an additional X chromosome, corresponding to a prevalence of 103 per 100,000 females; 27.9% had been clinically diagnosed. Females with 47,XXX had taller stature (+6.1 cm, p < 0.001), greater rate of outpatient encounters ( p = 0.026), higher odds of kidney disease (odds ratio [OR] = 12.3; 95% confidence interval [CI] 2.9–51.8), glaucoma (OR = 5.1; 95% CI 1.5–13.9), and congestive heart failure (OR = 5.6; 95% CI 1.4–24.2), and were more likely to be unemployed ( p = 0.008) with lower annual income ( p = 0.021) when compared with 46,XX controls of the same age and genetic ancestry. However, there were no differences in the rates of other encounter types, Charlson Comorbidity Index, all other medical and psychological diagnoses, military service history or quality of life metrics. In conclusion, in this aging and predominately undiagnosed sample, 47,XXX conferred few differences when compared with matched controls, offering a more reassuring perspective to the trisomy X literature.
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MAY THE SYSTEMIC IMMUNE-INFLAMMATION INDEX BE AN INDICATOR OF PREMATURE OVARIAN FAILURE?
Article
Full-text available
  • Feb 2023
Aim: This study aimed to determine whether there was a correlation between the systemic immune-inflammation index and ovarian reserve markers such as follicle stimulant hormone, estradiol, and anti-müllerian hormone. Methods: The study comprised 65 people with premature ovarian insufficiency and 71 controls with similar demographics. The concentrations of hemoglobin, hematocrit, platelets, white blood cells, neutrophils, and lymphocytes were evaluated. The neutrophil leukocyte ratio, platelet lymphocyte ratio, and systemic immune-inflammation index were calculated. The antral follicle count reserves of all patients were evaluated by transvaginal ultrasonography. An independent t-test was used for the comparison of the study and control groups. Correlations between variables were analyzed using Pearson's correlation test. A p value of 0.05 was considered significant. Results: The results of the neutrophil-to-lymphocyte ratio and the platelet-lymphocyte ratio showed a significant difference between the groups (p = 0.043). The Systemic Immune Inflammation Index value was the statistically significant difference found between the groups. There was a significant positive correlation between the systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, platelet-lymphocyte ratio, and follicle stimulant hormone, while a significant negative correlation was found between the systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, platelet-lymphocyte ratio, antral follicle count, and anti-mullerian hormone. Conclusions: Our study was the first in this field to reveal the relationship between premature ovarian failure and the systemic immune-inflammation index. According to our study results, the systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, and platelet-lymphocyte ratio are significantly higher in individuals with ovarian failure. It can be used as a marker for the diagnosis of premature ovarian insufficiency.
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Premature Ovarian Insufficiency
Article
  • Feb 2023
Natural menopause typically occurs between the ages of 46 to 55 years. Premature ovarian insufficiency or premature menopause refers to compromised ovarian follicular activity, occurring spontaneously or because of medical interventions, prior to the age of 40 years. The premature loss of estrogen leads to bothersome menopause symptoms and predisposes the women to multiple long-term health risks including a higher mortality risk. Hormone replacement therapy used until the natural age of menopause can help manage the symptoms effectively and can mitigate the long-term risk of estrogen deprivation to some extent. However, hormone replacement therapy is underutilized in this population due to the inappropriate extrapolation of potential risks that have been demonstrated with hormone therapy use in women after natural menopause. There is a large unmet need for educating patients and providers regarding the impact of premature ovarian insufficiency and the compelling need for its appropriate management.
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Neuropsychological and mental health concerns in a multicenter clinical sample of youth with turner syndrome
Article
  • Jan 2023
Clinical practice guidelines for individuals with Turner syndrome (TS) recommend screening for neuropsychological concerns (NC) and mental health concerns (MHC). However, current provider screening and referral patterns for NC and MHC are not well characterized. Additionally, prevalence of and risk factors for NC and MHC vary across studies. This multicenter chart review study examined the prevalence, risk factors for, and management of NC and MHC in a cohort of 631 patients with TS from three pediatric academic medical centers. NC and/or MHC were documented for 48.2% of patients. Neuropsychological evaluation recommendations were documented for 33.9% of patients; 65.4% of the sample subsequently completed these evaluations. Mental health care recommendations were documented in 35.0% of records; subsequent documentation indicated that 69.7% of these patients received such services. Most notably, rates of documented MHC, NC, and related referrals differed significantly by site, suggesting the need for standardized screening and referral practices. TS diagnosis in early childhood was associated with an increased risk of NC. Spontaneous menarche was associated with increased risk of MHC. Younger age at growth hormone initiation was associated with both increased risk of isolated NC and co‐occurring NC and MHC. Mosaic karyotype was associated with decreased risk of NC and MHC.
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Infertility and psychological distress: A critical review of the literature
Article
Full-text available
  • Dec 1997
This essay reviews the literature on the social psychological impact of infertility, paying special attention to the relationship between gender and the infertility experience. It is convenient to divide the literature into articles which explore the possibility that infertility may have psychological causes (Psychogenic Hypothesis) and those which examine the psychological consequences of infertility (Psychological Consequences Hypothesis). The psychogenic hypothesis is now rejected by most researchers, but a related hypothesis, which states that stress may be a causal factor in infertility, is worthy of exploration. The descriptive literature on the psychological consequences of infertility presents infertility as a devastating experience, especially for women. Attempts to test the psychological consequences hypothesis have produced more equivocal results. In general, studies which look for psychopathology have not found significant differences between the infertile and others. Studies which employ measures of stress and self-esteem have found significant differences. The psychological consequences literature is characterized by a number of flaws, including over sampling of women, small sample size, non-representative samples, failure to study those who have not sought treatment, primitive statistical techniques, and an over-reliance on self-reports. Studies on infertility and psychological distress need to take into consideration both the duration of infertility and the duration of treatment. Finding an appropriate set of "controls" is a particularly intractable problem for this area of research. In general, the psychological distress literature shows little regard for the social construction of infertility. By taking what should be understood as a characteristic of a social situation and transforming it into an individual trait, the literature presents what is essentially a medical model of the psycho-social impact of infertility. Most researchers conclude that infertility is a more stressful experience for women than it is for men. Most studies have found that the relationship between gender and infertility distress is not affected by which partner has the reproductive impairment. Future research needs to be better informed by theoretical considerations. Scholars need to pay more attention to the way the experience of infertility is conditioned by social structural realities. New ways need to be developed for better taking into account the processual nature of the infertility experience. Efforts need to be make to include under-studied portions of the infertile population. Finally, more effort needs to be made to better integrate the empirical study of the experience of infertility with important social policy questions.
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Selective Reduction in Cortical Bone Mineral Density in Turner Syndrome Independent of Ovarian Hormone Deficiency
Article
Full-text available
  • Jan 2004
Women with Turner syndrome (TS) are at risk for osteoporosis from ovarian failure and possibly from haploinsufficiency for bone-related X-chromosome genes. To establish whether cortical or trabecular bone is predominantly affected, and to control for the ovarian failure, we studied forearm bone mineral density (BMD) in 41 women with TS ages 18-45 yr and in 35 age-matched women with karyotypically normal premature ovarian failure (POF). We measured BMD at the 1/3 distal radius (D-Rad(1/3); predominantly cortical bone) and at the ultradistal radius (UD-Rad; predominantly trabecular bone) by dual x-ray absorptiometry. Women with TS had lower cortical BMD compared with POF (D-Rad(1/3) Z-score = -1.5 +/- 0.8 for TS and 0.08 +/- 0.7 for POF; P < 0.0001). In contrast, the primarily trabecular UD-Rad BMD was normal in TS and not significantly different from POF (Z-score = -0.62 +/- 1.1 for TS and -0.34 +/- 1.0 for POF; P = 0.26). The difference in cortical BMD remained after adjustment for height, age of puberty, lifetime estrogen exposure, and serum 25-hydroxyvitamin D (P = 0.0013). Cortical BMD was independent of serum IGF-I and -II, PTH, and testosterone in TS. We conclude that there is a selective deficiency in forearm cortical bone in TS that appears independent of ovarian hormone exposure and is probably related to X-chromosome gene(s) haploinsufficiency.
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The CES-D Scale: A Self-Report Depression Scale for Research in the General Population
Article
  • Jun 1977
  • APPL PSYCH MEAS
The CES-D scale is a short self-report scale designed to measure depressive symptomatology in the general population. The items of the scale are symptoms associated with depression which have been used in previously validated longer scales. The new scale was tested in household interview surveys and in psychiatric settings. It was found to have very high internal consistency and adequate test- retest repeatability. Validity was established by pat terns of correlations with other self-report measures, by correlations with clinical ratings of depression, and by relationships with other variables which support its construct validity. Reliability, validity, and factor structure were similar across a wide variety of demographic characteristics in the general population samples tested. The scale should be a useful tool for epidemiologic studies of de pression.
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Development and validation of measures of social phobia scrutiny fear and social interaction anxiety 1 1 Editor’s note: This article was written before the development of some contemporary measures of social phobia, such as the Social Phobia and Anxiety Inventory (Turner et al., 1989). We have invited this article for publication because of the growing interest in the scales described therein. S.T
Article
  • Apr 1998
  • BEHAV RES THER
The development and validation of the Social Phobia Scale (SPS) and the Social Interaction Anxiety Scale (SIAS) two companion measures for assessing social phobia fears is described. The SPS assesses fears of being scrutinised during routine activities (eating, drinking, writing, etc.), while the SIAS assesses fears of more general social interaction, the scales corresponding to the DSM-III-R descriptions of Social Phobia—Circumscribed and Generalised types, respectively. Both scales were shown to possess high levels of internal consistency and test–retest reliability. They discriminated between social phobia, agoraphobia and simple phobia samples, and between social phobia and normal samples. The scales correlated well with established measures of social anxiety, but were found to have low or non-significant (partial) correlations with established measures of depression, state and trait anxiety, locus of control, and social desirability. The scales were found to change with treatment and to remain stable in the face of no-treatment. It appears that these scales are valid, useful, and easily scored measures for clinical and research applications, and that they represent an improvement over existing measures of social phobia.
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Shyness Situations: Perspectives of a Diverse Sample of Shy Females
Article
  • Dec 1986
To determine whether shyness-eliciting situations identified by college students would generalize to a mote diverse sample, data were gathered from 187 shy females (14 to 58 yr. of age) who responded to a popular magazine's article about shyness. Coding of responses about shyness situations gave a set of categories highly congruent with previous research involving students. Engaging in conversations and encountering strangers or unfamiliar surroundings seem particularly problematic situations for shy people.
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Psychosocial Adjustment of Adult Women with Turner Syndrome
Article
This paper presents results from a detailed assessment of the psycho-social adaptation of a group of adult women with Turner syndrome. Thirty subjects, 21 to 48 years of age, participated in an evaluation of social and psychiatric status. The evaluation included a semi-structured interview designed to assess current social functioning and past psychiatric and social history. Subjects completed two self-report questionnaires as well: the Tennessee Self-Concept Scale and the Carroll Rating Scale for Depression. The results reveal a significant subgroup of subjects reporting major psychiatric difficulties and endorsing a considerably impaired sense of self-esteem. These women presented as very dissatisfied with themselves and their lives. These findings are not consistent with previous reports in which women with Turner syndrome have been described as having an unusually high tolerance for stress and being emotionally inert.
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Dimensions of Rosenburgs self - esteem scale
Article
  • May 1976
The dimensions of Rosenburg's scale of self-esteem (1965) were investigated via principal components and oblique factor analysis. Data from 479 students in a basic speech course yielded a two-factor solution. As the two factors appeared to identify only a response set, it was concluded the scale was unidimensional.
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Development and validation of measures of social phobia scrutiny fear and social interaction anxiety
Article
  • May 1998
  • BEHAV RES THER
The development and validation of the Social Phobia Scale (SPS) and the Social Interaction Anxiety Scale (SIAS) two companion measures for assessing social phobia fears is described. The SPS assesses fear of being scrutinised during routine activities (eating, drinking, writing, etc.), while the SIAS assesses fear of more general social interaction, the scales corresponding to the DSM-III-R descriptions of Social Phobia--Circumscribed and Generalised types, respectively. Both scales were shown to possess high levels of internal consistency and test-retest reliability. They discriminated between social phobia, agoraphobia and simple phobia samples, and between social phobia and normal samples. The scales correlated well with established measures of social anxiety, but were found to have low or non-significant (partial) correlations with established measures of depression, state and trait anxiety, locus of control, and social desirability. The scales were found to change with treatment and to remain stable in the face of no-treatment. It appears that these scales are valid, useful, and easily scored measures for clinical and research applications, and that they represent an improvement over existing measures of social phobia.
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Shyness: Relationship to social phobia and other psychiatric disorders
Article
  • Mar 2003
  • BEHAV RES THER
The relationship between shyness, social phobia and other psychiatric disorders was examined. The prevalence of social phobia was significantly higher among shy persons (18%) compared with non-shy persons (3%). However, the majority of shy individuals (82%) were not socially phobic. A significant and positive correlation was found between the severity of shyness and the presence of social phobia, but the data suggest that social phobia is not merely severe shyness. Social phobia was also positively and moderately correlated with introversion and neuroticism. Thus, shy persons with social phobia were shyer, more introverted, and more neurotic than other shy people, but none of these factors was sufficient to distinguish shy persons with social phobia from those without social phobia. The proportion of the shy group with psychiatric diagnoses other than social phobia was significantly higher than among the non-shy group, indicating that various diagnostic categories are prominent among the shy. The results are discussed in terms of the overlap in shyness and social phobia and the relationship of shyness to other psychiatric diagnoses and personality dimensions.
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