Management of Turner syndrome in adults

INTRODUCTION — Turner syndrome is one of the most common chromosomal anomalies in humans and represents an important cause of short stature and primary ovarian insufficiency (POI; early menopause) in females. It is caused by loss of part or all of an X chromosome.

This topic will review the management of adult women with Turner syndrome. The clinical manifestations and diagnosis of Turner syndrome and management in children and adolescents are reviewed separately. (See "Management of Turner syndrome in children and adolescents" and "Clinical manifestations and diagnosis of Turner syndrome".)

TRANSITION TO ADULT CARE — The transition from pediatric care to adult care is a crucial period during the health care management of the Turner syndrome patient. Unfortunately, few girls with Turner syndrome go on to receive optimal care and surveillance as adults [1,2]. Loss to follow-up is common, leading to insufficient monitoring of comorbidities and lack of estrogen therapy or other interventions [2,3].

A toolkit to assist with the transition to adult care was developed by the Endocrine Society in 2016 and includes forms for assessing patient readiness, knowledge, and skills, general recommendations to the adult care provider, and a summary of screening recommendations (table 1) [4].

In addition to discussing medical conditions associated with Turner syndrome (table 2), other important issues to address with the patient during the transition period include:

●Strategies and resources for managing learning difficulties, which continue into adult life. These resources may include educational consulting and support, as well as vocational counseling. (See 'Neuropsychiatric' below.)

●Resources for psychosocial support. The team should specifically encourage the patient to engage with Turner syndrome support groups for emotional support and to help empower the patient to stay engaged with their health maintenance. (See 'Neuropsychiatric' below.)

As patients transition to adult providers, the communication and counseling should be tailored to the patient's maturity level and is ideally achieved by a multidisciplinary specialty team that includes adult and pediatric endocrinology, mental health, and obstetrics and gynecology providers [5-8]. In one retrospective cohort study of 82 patients with Turner syndrome receiving care at a multidisciplinary specialty clinic, patients were more likely to be started on estrogen therapy and have comorbidities identified than similar women receiving care at primary care facilities [8].

APPROACH TO THE ADULT PATIENT WITH TURNER SYNDROME

Goals — The overarching goals of caring for the adult patient with Turner syndrome include:

●Management of cardiovascular disorders (congenital and noncongenital), as well as continued surveillance to monitor for valvular disease and to detect aortic root dilatation or other cardiovascular anomalies (algorithm 1 and table 3). (See 'Cardiovascular health' below.)

●Long-term treatment with estrogen-progestin therapy to prevent adverse consequences of estrogen deficiency including bone loss and a possible increased risk for early coronary heart disease, excess mortality, cognitive decline, and dementia. (See 'Estradiol therapy' below.)

●Management of fertility issues and potential for pregnancy if desired (which is associated with a high risk of cardiac complications). (See 'Management of fertility and pregnancy' below.)

●Surveillance for and management of comorbidities that may include autoimmune thyroid disease, type 2 diabetes mellitus, hearing loss, and abnormal liver enzymes (table 2) [9]. (See 'Surveillance for comorbidities' below.)

Cardiovascular health — Cardiovascular disease presents the most serious health problem for adult women with Turner syndrome and substantially contributes to the increased mortality rates for affected individuals. The morbidity and mortality are due to increased risks for cardiovascular malformations, compounded by renal abnormalities and hypertension, leading to increased risk for aortic dilatation and dissection [10]. (See "Clinical manifestations and diagnosis of Turner syndrome", section on 'Cardiovascular disease'.)

Monitoring/surveillance — Ideally, all patients with Turner syndrome, especially those with identified cardiac anomalies, should have ongoing care with a cardiologist, preferably one who has expertise in congenital heart disease [10,11]. (See "Clinical manifestations and diagnosis of Turner syndrome", section on 'Cardiovascular disease'.)

Blood pressure should be monitored annually, and patients should undergo a full cardiac examination, with additional imaging studies (transthoracic echocardiography or, and often more desirable, cardiac magnetic resonance imaging [MRI]) to monitor valvular disease and to detect aortic root dilatation or other cardiovascular anomalies (algorithm 1 and table 1) [12-16]. If aortic dilatation is identified, patients should be re-evaluated to optimize medical treatment. Management may include beta blockers, exercise restriction, and aggressive blood pressure control, as outlined in a statement on cardiovascular health in Turner syndrome from the American Heart Association [17].

Electrocardiography with QTc measurement is done at diagnosis, and repeat assessment will depend on the presence or absence of QT prolongation or other arrhythmia. Repeat electrocardiography should also be done one to two weeks after initiation of therapy with QT-prolonging drugs. (See "Management of Turner syndrome in children and adolescents", section on 'Management of specific cardiovascular abnormalities' and 'Other management issues' below.)

The imaging studies are done to detect cardiovascular anomalies such as coarctation of the aorta, bicuspid aortic valve, or partial anomalous pulmonary venous return (PAPVR). Cardiac MRI is valuable for both screening and surveillance, especially to detect abnormalities such as a dilated aorta and elongated transverse aortic arch, as well as milder aortic coarctation and PAPVR.

Repeat imaging with echocardiography and cardiac MRI is performed periodically. The frequency of imaging studies depends upon the presence or absence of existing cardiovascular abnormalities, such as coarctation of the aorta, bicuspid aortic valve, or hypertension, and the aortic size index (ASI) (algorithm 1). For example, women without cardiovascular abnormalities on MRI at baseline and whose ASI is <2 cm/m² are considered low risk. Imaging studies for these women are recommended every 5 to 10 years. Imaging studies are recommended more often for those at moderate to high risk, as outlined in the algorithm (algorithm 1).

In addition, imaging studies are recommended before attempting pregnancy and/or if hypertension develops (table 3) [12,15,16]. (See 'Management of fertility and pregnancy' below.)

An overview of the management of coarctation of the aorta in women, including management before and during pregnancy, is discussed separately. (See "Management of coarctation of the aorta".)

Women with Turner syndrome are also at substantially increased risk for noncongenital cardiovascular disease, which is an important contributor to their excess mortality. Therefore, all women should have close monitoring and vigorous intervention for cardiovascular risk factors, including hypertension, dyslipidemia, prediabetes, or diabetes mellitus. (See 'Mortality' below and 'Surveillance for comorbidities' below and "Clinical manifestations and diagnosis of Turner syndrome", section on 'Cardiovascular disease'.)

Management

Aortic dilatation — If serial imaging shows a marked increase in aortic diameter that leads to an ASI >95^th to 99^th percentile (≥2.3 cm/m²), patients should be evaluated to optimize medical treatment and to lessen the risk of aortic events, although data on this issue are limited [18-20] (algorithm 1). Because dissection of the aorta may occur at smaller aortic dimensions in Turner syndrome patients and at an earlier age, it is reasonable to begin prophylactic antihypertensive therapy earlier than for other patient groups [16]. (See "Management of Turner syndrome in children and adolescents", section on 'Hypertension'.)

If aortic dilatation is identified on imaging, management may include beta blockers, exercise restriction, and aggressive blood pressure control, similar to management of this issue in patients with Marfan syndrome. Any complaint of chest pain should be evaluated urgently by a specialist because it may be a symptom of early dissection. (See "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders" and "Clinical features and diagnosis of acute aortic dissection".)

Elective surgical repair may be an option for some patients, particularly if aortic dilation is rapidly expanding (ie, an increase of more than 0.5 cm in one year). The techniques used and perioperative care are similar to those used for other patients with aortic dilatation and dissection.(See "Management of Turner syndrome in children and adolescents", section on 'Hypertension' and "Management of Marfan syndrome and related disorders" and "Management of thoracic aortic aneurysm in adults".)

Hypertension — Hypertension is reported in 30 to 50 percent of adult Turner syndrome patients and is associated with an increased risk of stroke and aortic dissection (table 2) [16] (see "Clinical manifestations and diagnosis of Turner syndrome", section on 'Hypertension'). Blood pressure should therefore be monitored at every clinical visit; ideally, blood pressure should be measured manually because automated blood pressure monitoring may result in falsely high readings. Twenty-four-hour Holter monitoring may be helpful to confirm hypertension in certain patients who are particularly anxious in the clinician's office.

If hypertension develops, treatment should be initiated, including lifestyle modification and weight loss if indicated. Patients should also be evaluated for causes of hypertension such as kidney disease, obstructive uropathy, and previously undetected coarctation of the aorta.

Most experts suggest starting therapy for blood pressures that are persistently in the hypertensive range and targeting a low-normal blood pressure [16,18]. Hypertension is defined as blood pressure >130/80 mmHg for adults and children >13 years [21]. Initial therapy usually consists of beta blockers, unless otherwise contraindicated, due to their favorable effect on aortic dilatation in Marfan syndrome, although evidence in Turner syndrome is limited [6,7]. Angiotensin-converting enzyme (ACE) inhibitors are a reasonable alternative. (See "Management of Marfan syndrome and related disorders", section on 'Drug therapy'.)

Other management issues

●Patients found to have coarctation of the aorta should almost always undergo surgical correction. (See "Clinical manifestations and diagnosis of coarctation of the aorta" and "Management of coarctation of the aorta", section on 'Choice of intervention'.)

A percutaneous stenting approach of aortic coarctation in Turner syndrome patients can be effective, but it is associated with serious morbidity and mortality [22].

●For those with a conduction abnormality shown on an electrocardiogram (prolonged QTc interval), drugs that prolong QTc interval should be avoided (eg, antifungal agents, such as fluconazole; metronidazole; fluoroquinolones, such as ciprofloxacin; macrolide antibiotics, such as azithromycin; certain human immunodeficiency virus (HIV) antiviral agents; and others). (See "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management" and "Management of Turner syndrome in children and adolescents", section on 'Management of specific cardiovascular abnormalities'.)

●Antimicrobial prophylaxis is not required for most Turner syndrome patients with valvular heart disease, including those with bicuspid aortic valve. This is based on the 2007 American Heart Association (AHA) guidelines on the prevention of bacterial endocarditis, which recommend that only patients with the highest risk for the development of endocarditis receive antimicrobial prophylaxis [23]. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

Mortality — Overall mortality rates in patients with Turner syndrome are increased approximately threefold when compared with the general population. Cardiovascular disease accounts for approximately 40 percent of deaths, but the excess risk occurs for most major causes of death [24,25]. The increased mortality is seen at all ages, but it is highest in older adulthood (figure 1) [25]. Estrogen deficiency is also thought to play a role. The excess mortality of Turner syndrome is discussed in detail separately. (See "Clinical manifestations and diagnosis of Turner syndrome", section on 'Mortality' and 'Estradiol therapy' below.)

Reproductive health

Estradiol therapy — Unless there is an absolute contraindication, such as breast cancer, women with Turner syndrome should receive estradiol therapy to prevent bone loss and reduce the risk of osteoporosis, cardiovascular disease, and urogenital atrophy and to maintain sexual health and quality of life (table 2). The clinical consequences of long-term estrogen deficiency and the practical aspects of estrogen therapy in women with primary ovarian insufficiency (POI) are reviewed in detail separately. (See "Clinical manifestations and diagnosis of primary ovarian insufficiency (premature ovarian failure)", section on 'Bone loss and osteoporosis' and "Management of primary ovarian insufficiency (premature ovarian failure)", section on 'Importance of estrogen therapy'.)

Estradiol therapy may also be important to reduce the increased mortality risk seen in women with Turner syndrome. Although most of the excess mortality is due to cardiovascular complications, estradiol deficiency throughout life may play a role in the noncongenital cardiovascular complications. (See 'Mortality' above and "Clinical manifestations and diagnosis of Turner syndrome", section on 'Mortality'.)

Estradiol regimens for adult women with Turner syndrome are the same as for other women with POI and are reviewed separately (see "Management of primary ovarian insufficiency (premature ovarian failure)", section on 'Importance of estrogen therapy'). We prefer transdermal estradiol patches (100 mcg per patch is a reasonable dose for young adult women with Turner syndrome) along with micronized progesterone (200 mg daily for 12 days) administered orally (table 4).

While some women with early POI and residual ovarian function sometimes use combined oral contraceptives (COCs) for contraception, most women with Turner syndrome have complete ovarian failure and do not require contraception. In addition, limited data suggest women with Turner syndrome are at increased risk for venous thromboembolism [26], and therefore, COCs should be avoided. (See "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Cardiovascular effects'.)

Duration — In young women with POI, including those with Turner syndrome, we suggest continuing estradiol-progestin therapy until age 50 or 51 years, the average age of menopause, to mimic the estradiol secretion of women with functioning ovaries. (See "Management of primary ovarian insufficiency (premature ovarian failure)".)

Unfortunately, many women do not receive the appropriate duration of hormone therapy. In a report of 50 adult women with Turner syndrome with a mean age of 40 years, only 34 (68 percent) were still taking estrogen. Among the 16 women not taking estrogen, 11 had stopped because they were unaware of the health benefits of estrogen and five were advised against its use by their clinicians [27]. Six of 16 women in the non-estrogen group had osteoporosis (three with vertebral compression fractures), compared with 0 of 34 in the estrogen group.

In a second study of 78 patients with Turner syndrome referred to an adult specialty clinic (median age 28.5 years), 37 percent had either stopped estrogen on their own or had been advised to stop by their clinicians [6]. One-third of the women had already experienced osteoporosis-related fractures.

Safety — Many women express concerns about the potential risks of cardiovascular complications and breast cancer with long-term estrogen therapy because of reports from the Women's Health Initiative (WHI), a study of menopausal hormone therapy (MHT) in older postmenopausal women (average age 63 years) (see "Menopausal hormone therapy: Benefits and risks"). However, the results of the WHI are not clinically relevant for young women with POI due to Turner syndrome or other causes of POI, in whom the benefits of MHT outweigh the risks.

Data from women with Turner syndrome further include the following:

●In a report of 62 patients with Turner syndrome who had been on hormone therapy for 20 to 40 years, no cases of breast cancer were identified [28]. (See "Management of primary ovarian insufficiency (premature ovarian failure)".)

●There had been concern that treatment with estrogen might worsen hepatic disease in patients with elevated liver enzymes. However, in a study of 80 women (ages 17 to 49 years) with Turner syndrome, 44 percent of whom had elevated liver enzymes, hormone therapy (estrogen plus progestin) was associated with improvement in liver enzymes [29].

Management of fertility and pregnancy — Most women with Turner syndrome are infertile because of ovarian follicular depletion. Spontaneous pregnancies are occasionally seen, and a number of women now undergo in vitro fertilization (IVF) with donor oocytes to try to conceive. However, there is an increased risk of aortic dissection or rupture in women with Turner syndrome during pregnancy or in the immediate postpartum period [30]; the risk of death may be as high as 2 percent. For women with mosaic Turner syndrome, experimental techniques include cryopreservation of oocytes (if there is evidence of remaining ovarian follicles based on anti-müllerian hormone [AMH] and follicle-stimulating hormone [FSH] levels) [31] or cryopreservation of ovarian tissue [32].

Preconception counseling and evaluation — Because of the potential risk of aortic dissection, women with Turner syndrome must undergo a complete medical evaluation before attempting pregnancy, with particular attention paid to cardiovascular and renal function [16,33]. One group, the American Society of Reproductive Medicine (ASRM), considers Turner syndrome a relative contraindication for pregnancy, but an absolute contraindication if there is a documented cardiac anomaly [33].

A consensus meeting that included expert input from cardiologists, medical and reproductive endocrinologists, and maternal-fetal medicine experts published clinical practice guidelines in 2017 [16]. Major recommendations related to pregnancy included:

●Women with Turner syndrome should be counseled about the high cardiovascular risks associated with pregnancy.

●Imaging of the thoracic aorta and heart with transthoracic echocardiography (TTE) and cardiac MRI must be performed within two years before planned pregnancy or assisted reproductive technologies (ART).

●ART or spontaneous conception should be avoided in women with an ascending ASI of >2.5 cm/m² or an ascending ASI 2 to 2.5 cm/m² with associated risk factors for aorta dilatation, which include bicuspid aortic valve, elongation of the transverse aorta, coarctation of the aorta, and hypertension.

●Additional recommendations regarding the risks and precautions for pregnancy in women with Turner syndrome can be found in the 2017 Turner syndrome clinical practice guidelines publication [16].

Spontaneous pregnancies — As noted, most women with Turner syndrome are infertile because of ovarian follicular depletion, but occasional spontaneous pregnancies occur. In one cohort of 480 women with Turner syndrome, 27 women (5.6 percent) had a total of 52 spontaneous pregnancies [34-37]. Predictors of pregnancy included spontaneous menarche and mosaic karyotype. Of the 52 pregnancies, there were 16 miscarriages (30.8 percent), one intrauterine fetal death related to severe growth restriction, five pregnancy terminations, and 30 live births (in 18 women). These pregnancies are associated with a higher prevalence of hypertensive disorders of pregnancy, including preeclampsia and eclampsia.

IVF with cryopreserved oocytes — Some postpubertal adolescents or women with Turner syndrome and mosaic karyotypes retain sufficient ovarian function to produce oocytes with ovarian stimulation followed by oocyte retrieval and cryopreservation for later in vitro fertilization (IVF). In a study of 35 cycles of IVF in 22 women with mosaic Turner syndrome using autologous oocytes, the live birth rate was only 5.7 percent [38]. (See "Management of Turner syndrome in children and adolescents", section on 'Cryopreservation of ovarian tissue or oocytes'.)

IVF with donor oocytes — In vitro fertilization (IVF) with donor oocytes results in considerably better pregnancy rates than IVF with autologous oocytes [16,39,40]. However, as noted, there are significant cardiac risks associated with pregnancy in all women with Turner syndrome. Therefore, this approach should only be considered after careful counseling and a thorough evaluation by a multidisciplinary team that includes maternal-fetal medicine specialists, reproductive endocrinologists, and cardiologists with experience in managing patients with Turner syndrome [16,41,42]. (See 'Preconception counseling and evaluation' above.)

Single embryo transfer is mandatory in these patients, given the increased medical risks associated with multiple gestations. The rate of cesarean section is also quite high in these pregnancies.

The management of coarctation prior to and during pregnancy in all women is discussed separately. (See "Management of coarctation of the aorta", section on 'Pregnancy'.)

Outcomes — In a systematic review of 11 studies including 179 patients with Turner syndrome undergoing IVF with donor oocytes, the following results were seen [16]:

●The pooled clinical pregnancy rate per embryo transfer was 28 percent (similar to women without Turner syndrome).

●The incidence of hypertensive disorders of pregnancy was between 35 and 67 percent in singleton pregnancies (versus 13 to 39 percent in women without Turner syndrome) and as high as 100 percent in multiple pregnancies.

●The reported incidence of preeclampsia ranged from 18 to 44 percent and 75 to 100 percent in singleton and multiple pregnancies, respectively.

●The cesarean delivery rate for singleton pregnancies was 82 to 100 percent (versus 31 to 85 percent for women without Turner syndrome). The increased frequency is related to maternal cardiac disease as well as cephalopelvic disproportion in women with short stature.

In a cohort study published after the pooled analysis [39], 106 women with Turner syndrome underwent IVF with oocyte donation, resulting in 122 deliveries. Outcomes included multiple gestations in 7.4 percent and hypertensive disorder of pregnancy in 35 percent, including preeclampsia in 20.5 percent. Ten women had a known cardiac defect before pregnancy, although only 49 percent had a prepregnancy cardiac evaluation within two years before pregnancy and only 29 percent had an echocardiogram or cardiac MRI during pregnancy. Potentially life-threatening complications occurred in four patients (3.3 percent). In spite of suboptimal preconception evaluation and screening, no maternal deaths were reported. The rate of multiple gestations in this study was lower than what is typically reported in oocyte donation studies of women without Turner syndrome; single embryo transfer is mandatory with Turner syndrome, but not with other patients.

Medical management during pregnancy — The medical management of pregnant women with Turner syndrome focuses on blood pressure control. Recommendations for antihypertensives do not differ from those for pregnant women who do not have Turner syndrome. (See "Treatment of hypertension in pregnant and postpartum patients".)

Because of the high risk of preeclampsia, women should receive 75 mg aspirin daily from 12 weeks of gestation until delivery. In addition, ultrasound screening for intrauterine growth restriction (IUGR) is typically done, given the increased risk in this population. In one report of 93 women with Turner syndrome who conceived with donor oocytes, the frequency of IUGR was 27.5 percent (26 of 93 pregnancies) [43,44]. (See "Preeclampsia: Prevention", section on 'Low-dose aspirin' and "Fetal growth restriction: Screening and diagnosis".)

Delivery — A delivery plan should be made by a multidisciplinary team consisting of at least an obstetrician/maternal-fetal medicine specialist, cardiologist, and anesthesiologist, all with expertise in pregnancy in the context of maternal heart disease and/or aortopathy. Clinical practice guidelines suggest that women with an ascending ASI >2.5 cm/m² undergo cesarean delivery [16]. Vaginal delivery is the preferred mode of delivery in other women, with cesarean delivery for standard obstetric indications.

Surveillance for comorbidities — Women with Turner syndrome should be seen on a yearly basis for physical examination and biochemical testing for thyroid disease, glucose intolerance, dyslipidemia, and liver abnormalities [9]. In addition, screening for hearing loss and cardiovascular anomalies should be done at regular intervals. Detailed recommendations have been published by the International Turner Syndrome Consensus Group (algorithm 1 and table 1) [16].

Routine laboratory monitoring is recommended, as outlined in the table (table 1):

Diabetes mellitus — Fasting plasma glucose, glycated hemoglobin (A1C), and lipid panel annually to monitor for metabolic syndrome and diabetes mellitus. Guidance on nutrition and physical activity should be provided to all patients and particularly to those with evidence of metabolic syndrome (table 1) [13,14]. (See "Clinical manifestations and diagnosis of Turner syndrome", section on 'Metabolic syndrome and diabetes mellitus'.)

Patents should also be weighed every year. Weight management is an essential health intervention as many comorbidities are obesity related.

Liver disease — Liver aminotransferases (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and gamma glutamyl transpeptidase [GGTP]) annually (table 1) (see "Clinical manifestations and diagnosis of Turner syndrome", section on 'Abnormal liver enzymes'). In most patients, the aminotransferase elevations remain mild. Referral to a liver disease specialist should be considered for those patients with rising aminotransferase concentrations. If significant elevations are confirmed, liver ultrasonography may be performed to screen for steatosis, nodules, or portal hypertension and to assess liver stiffness.

Autoimmune hypothyroidism — Thyroid function (thyroid-stimulating hormone [TSH] and free thyroxine [T4]) annually (table 1). (See "Clinical manifestations and diagnosis of Turner syndrome", section on 'Autoimmune disorders'.)

Celiac disease — Clinical practice guidelines suggest screening by measuring tissue transglutaminase immunoglobulin (Ig) A antibodies (tTG-IgA, usually combined with total IgA), beginning in early childhood (around two years of age) and repeating every two years throughout childhood (table 1) [12,16]. During early adulthood, screening should be repeated if symptoms suggestive of celiac disease arise. The risk of celiac disease is modestly increased in Turner syndrome, with approximately 4 to 6 percent of patients affected. (See "Clinical manifestations and diagnosis of Turner syndrome", section on 'Autoimmune disorders'.)

Bone health — Bone mineral density (BMD) should be evaluated using dual-energy x-ray absorptiometry (DXA) at the first visit with the adult provider. In addition, serum 25-hydroxyvitamin D should be measured every three to five years in adult patients (table 1) [16]. Maintaining recommended serum levels of 25-hydroxyvitamin D is important because girls and women with Turner syndrome have an increased risk of fracture even with a normal BMD. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Criteria to define optimal 25(OH)D'.)

Women with Turner syndrome have an increased risk for osteoporosis and fractures. Contributors include inadequate estrogen therapy and probably an estrogen-independent defect in cortical bone in these patients. Important preventive measures include optimal estrogen replacement and counseling to ensure recommended intake of calcium and vitamin D and weightbearing exercise. Women who meet these goals typically have normal BMD and are able to maintain this long term [45]. (See "Clinical manifestations and diagnosis of Turner syndrome", section on 'Osteoporosis and bone health'.)

Conventional BMD measurements (eg, DXA) can underestimate the true bone density of individuals with short stature [46]. However, we can use DXA scans to monitor bone density in response to estrogen therapy. If BMD is abnormal, further evaluation and treatment are the same as for other patients with low bone density or osteoporosis. If BMD is low when the patient is first evaluated, we suggest performing a DXA every five years once adult estradiol replacement therapy has been instituted. If BMD is normal, additional follow-up is done when the patient stops estradiol replacement (around 50 years of age). (See "Evaluation and treatment of premenopausal osteoporosis".)

Audiology testing — Regular evaluation of hearing (every three to five years) is essential for women with Turner syndrome (table 1) [12,14,16]. Sensorineural hearing impairment, predominantly at a frequency of 1000 to 2000 Hz (sensorineural dip), has been noted in more than 50 percent of adult Turner syndrome patients. This sensorineural hearing loss may be superimposed on conductive loss due to frequent otitis media in childhood and may also be complicated by the development of cholesteatoma in some patients. Early detection of hearing impairment and treatment with hearing aids is important to minimize the adverse effects on learning and social function [47]. (See "Clinical manifestations and diagnosis of Turner syndrome", section on 'Hearing and ear abnormalities'.)

Neuropsychiatric — Neuropsychology and allied behavioral health services should be integrated into the care for girls and women with Turner syndrome [16]. Most individuals with Turner syndrome have normal intelligence, but girls with a ring X chromosome have a higher risk for intellectual disabilities [48]. Some patients may have attention deficit disorder and difficulties with visual-spatial organization (including problems with mathematics and reverse parallel-parking), social cognition, and nonverbal problem-solving tasks. Cognitive behavioral therapy may be helpful for those with executive function issues (table 1) [16]. (See "Clinical manifestations and diagnosis of Turner syndrome", section on 'Psychologic and educational issues'.)

Skin — A yearly skin exam should be done to assess for keloid and changes in pigmented nevi (table 1). (See "Clinical manifestations and diagnosis of Turner syndrome", section on 'Skin'.)

RESOURCES AND INFORMATION — Information and support for patients and their families can be obtained from:

Turner Syndrome Society of the United States

Tel: 1-800-365-9944

Turner Syndrome Foundation

Tel: 1-800-594-4585

Turner Syndrome Society of Canada

Tel: 1-800-465-6744

Turner Syndrome Society of UK

Tel: +44-0141-952-8006

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Turner syndrome".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Turner syndrome (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Turner syndrome is one of the most common chromosomal anomalies in humans and represents an important cause of short stature and primary ovarian insufficiency (POI) in females. It is caused by loss of part or all of an X chromosome. (See 'Introduction' above.)

●Cardiovascular disease presents the most serious health problem for women with Turner syndrome and substantially contributes to the increased mortality rates for affected individuals. The morbidity and mortality are due to increased risks for cardiovascular malformations, compounded by renal abnormalities and hypertension, leading to increased risk for aortic dilatation and dissection. (See 'Cardiovascular health' above.)

Ideally, all patients with Turner syndrome (especially those with identified cardiac anomalies) should have ongoing care with a cardiologist, preferably one who has expertise in congenital heart disease.

Imaging with transthoracic echocardiography and cardiac magnetic resonance imaging (MRI) is performed periodically. The frequency of imaging studies depends upon the presence or absence of existing cardiovascular abnormalities, such as coarctation of the aorta, bicuspid aortic valve, or hypertension, and the aortic size index (ASI) (algorithm 1). (See 'Monitoring/surveillance' above.)

●Women with Turner syndrome have POI, also known as premature ovarian failure. Unless there is an absolute contraindication, we suggest estradiol-progestin therapy to reduce the risk of osteoporosis and urogenital atrophy and to maintain sexual health (Grade 2B). We suggest that these women continue therapy until the average age of menopause (ie, approximately 50 or 51 years) (Grade 2B). (See 'Estradiol therapy' above.)

●Most women with Turner syndrome are infertile but can achieve fertility with in vitro fertilization (IVF) with donor oocytes. However, there are serious cardiovascular risks during and after pregnancy, the most important of which is the risk of aortic dissection. Cardiovascular evaluation is essential before considering pregnancy (algorithm 1). (See 'Management of fertility and pregnancy' above.)

●In addition to monitoring for cardiovascular complications, patients with Turner syndrome should have ongoing monitoring for other important health issues (table 1). (See 'Surveillance for comorbidities' above.)