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Departments of Molecular Medicine and Surgery (A.N., L.F., H.Fa., M.T.) and Women and Child Health (K.H.), Karolinska Institutet, SE-171 76 Stockholm, Sweden; Pediatric Surgery (A.N.), Astrid Lindgren Children Hospital, and Department of Endocrinology, Metabolism and Diabetes (H.Fa., M.T.), Karolinska University Hospital, SE-171 76 Stockholm, Sweden; Pediatric Surgery (G.H.), Queen Silvia Children’s Hospital, SE-416 85 Gothenburg, Sweden; Department of Clinical Sciences (L.F.), Karolinska Institutet, Danderyds Hospital, Division of Psychiatry, SE-182 87 Stockholm, Sweden; and Departments of Endocrinology (H.Fi.) and Obstetrics and Gynecology (P.O.J.), Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden
Address all correspondence and requests for reprints to: Agneta Nordenskjöld, CMM 02, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. E-mail: agneta.nordenskjold{at}ki.se.
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Abstract |
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Objective/Patients: A follow-up study on 62 CAH women aged 18–63 yr and 62 age-matched controls to correlate findings of both operative method and mutation was performed.
Design: Semistructured interviews were performed in cases and controls, as well as a gynecological examination in the cases. The results were correlated with disease-causing mutations and earlier surgical procedures if performed.
Setting: The study was conducted at university hospital referral clinics.
Main Outcome Measures: Gynecological examination in all cases correlated to previous surgery (n = 49), type of mutation, and questionnaire responses.
Results: Half of the CAH women claimed that the disease affected their sex life. The women were less satisfied with their genitals, whether operated or not. Clitoris size and functions were affected by the surgical method. Five women had a clinically evident vaginal stenosis on examination. However, almost half of patients experienced a narrow vagina. The overall psychosexual aspects of life were affected in these patients with later sexual debut, fewer pregnancies and children, and an increased incidence of homosexuality. These quality of life factors were correlated to the severity of the mutations.
Conclusions: The overall quality of life in adult women with CAH is affected both by the type of mutation and operative procedure. Indications for clitoroplasty should be restrictive. Medical, surgical, and psychological treatment should be centralized.
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Introduction |
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Several techniques have been used to correct clitoral hypertrophy. In the past, clitoral amputation was performed, but with increasing awareness of the importance of the clitoris for female sexuality, more refined procedures were developed. Great efforts are now made to provide satisfactory cosmetic result without sacrificing sensation and vascularity of the clitoris by removing erectile subtunical tissue, sparing as much as possible of the dorsal nerves, and perform a ventral glans reduction if needed (14).
Traditionally, vaginoplasty was performed using two basic procedures. The cutback vaginoplasty is a simple opening of a short common channel and the flap vaginoplasty using perineal skin to widen the introitus, reviewed by Rink and Adams (15).
Follow-up studies on women with CAH are important and increase general knowledge to improve treatment. They are also helpful in providing information to patients and families. The knowledge of long-term outcome is especially crucial for patients who are treated in early childhood and who will not fully benefit from their surgical treatment until they are sexually active. Several studies have included few and often only young adult patients, and are devoid of mutation data. The immediate correlation between phenotype and genotype is recognized, but it is not known whether the severity of mutation also correlates to later quality of life factors for the patients. In this Swedish study, 62 adult women with CAH were investigated concerning gynecological status and psychosexual conditions of life, and both factors were correlated to earlier surgical treatment and the type of mutation.
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Subjects and Methods |
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All CAH women were analyzed for mutations with the mildest of the two mutations as representative of the genotype (mutation). There were 14 women who had a salt-wasting (SW), potentially life-threatening form of CAH (corresponding to no enzyme activity), 15 had an I2splice-mutation [a few percentage of normal enzyme activity, mutation that causes clinical phenotypes of either SW or simple virilizing (SV)], 27 had mutations corresponding to the SV form of CAH, and six had the nonclassical (NC) form. In two of the cases, the classification was based on clinical data due to the mutation being unique and not previously characterized (L308F and R233G). Age of onset and initial symptom varied with the severity of the mutation as previously described (16).
All women were examined as outpatients between October 2002 and January 2005. They filled in a semistructured questionnaire (120 questions) concerning social life, fertility, sexuality, surgery, and the function of the clitoris and vagina, as well as satisfaction with the result and how they had experienced the health care as children. Furthermore, the women were asked about their opinion concerning timing of feminizing surgery. An English translation of the questionnaire can be provided on request. An endocrinologist performed physical examination, and blood and urine were sampled (16).
A gynecologist and a pediatric surgeon examined the women with CAH, but not the controls, to evaluate the cosmetic result of the external genitalia (photographed when permitted by the patient), as well as the size and function of the clitoris and vagina. The women’s subjective experience of clitoral sensitivity was tested with a small cotton stick on defined genital regions with the sensitivity of the left inner thigh as a reference point. The medical history charts concerning all surgical procedures were studied with the permission of the cases and were evaluated for comparison with the postoperative result. All these results have also been correlated to mutation data, categorized in four genotypic groups: SW, I2splice, SV, and NC. We also compared women older and younger than 30 yr. The Research Ethics Committees in Stockholm and Gothenburg approved the study. All participants gave written informed consent.
Statistics
The CAH patients were individually matched with control women, and, thus, data were considered as paired. In comparisons between the CAH patients and their controls, the McNemar or Sign test was performed for categorical data and the paired t test or Wilcoxon matched pair test for continuous data. The differences between the pairs were recorded according to the following when data are nominal or ordinal: –1 or +1 for discordant pairs, and 0 for equal pairs. If the variables were continuous, the differences were calculated from the data. The 
2 test was used to compare different subgroups with respect to the differences in pairs for categorical data, and the Mann-Whitney U, Kruskal-Wallis, or two-sample t test for continuous data. A P value less than 0.05 was considered statistically significant.
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Results |
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All medical histories concerning surgical procedures were requested (n > 154), and all but five were retrieved. The missing ones were predominantly the first surgical procedure on the oldest cases. The correlation between mutation and initial Prader stage is summarized in Table 1
. A total of 49 CAH women was surgically corrected with clitoroplasty and/or vaginoplasty. There were 16 who were operated on only once, and of those 10 were operated on at puberty. Fourteen were operated on twice, and four each was operated on three and four times, respectively. There were 11 women who had had surgery between five and more than 10 times. Nine patients had their primary operation at puberty, and 25 (51%) had complementary surgery at puberty. In the SW and I2splice genotype groups, the girls were most frequently operated (28 of the 29) on as well as reoperated on, and with the highest rate of complications, such as fistulas. The date of the last surgery occurred between 1 and 49 yr ago at examination and only eight within the last 5 yr. A summary of the operative procedures and mutations is presented (Fig. 1).
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Surgery of the clitoris
Clitoroplasty was performed on 38 girls. The first operation was usually performed from 6 months to 9 yr of age. Three women chose to be operated on due to a large clitoris between the age of 17 and 20 yr.
There were four main procedures used to diminish the size of the clitoris: amputation, placing the corpora sc without any resection (recession), raphy with ventral resection and forming a hairpin structure of the remains, and partial corporal body resection (15, 17). The surgical procedures to reduce the size of the clitoris were chosen depending on the year the surgery was performed and depending on local tradition. Amputation (n = 8) was performed mainly during the 1970s in six different cities and by eight different surgeons. Recession of the clitoral body (n = 12) was mainly performed in one pediatric surgery department and by four different surgeons around 1970. Partial corporeal resection, the method of choice since approximately 1975, was performed in 18 cases by 10 different surgeons (pediatric or plastic surgeons) in four different hospitals. Altogether, 19 surgeons performed the first feminizing surgery in 12 different clinics. Nine women had their clitoris reoperated on, and three women were reoperated on twice due to an unsatisfactory result.
The length of the clitoris was correlated to the surgical procedure, and, unless amputated, it was longer than a normal-sized clitoris: 16 ± 4.3 mm, as reported by Verkauf et al. (18); or 19.1 ± 8.7 mm, as reported by Lloyd et al. (19) (Table 2). Normal-sized clitoris was found in 17 cases (six nonoperated). In eight cases the clitoris was subnormally sized (<11.5 mm) (four amputated, one not operated). In 36 (or 27) cases, the clitoris was larger than normal [>20.5 mm (or > 28 mm)], and of these, 17 (or 14) were not operated on, two (or one) were amputated, eight (or six) had been operated on with partial resection, and eight (or six) with the sc recession method.
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). The difference becomes significant when all surgical procedures are considered (P = 0.006), and when surgery and nonsurgery are compared (P = 0.07; Fisher’s exact test). These five women had either been amputated, or operated on twice or three times on the clitoris. The women that had the clitoris operated on indicated a reduced sensitivity in the genital region, with lesser sensitivity on the clitoris. This was more pronounced when comparing amputated and sc placed clitoris with nonoperated clitoris.
In addition, different surgical procedures affected sensitivity differently. The women that had been amputated described diminished sensitivity of the glans region of clitoris compared with nonoperated, but sensitivity was preserved dorsally. A sc placed clitoris (no resection) was also described as less sensitive, probably due to scarred tissue, but all could experience orgasm. The best procedure for preserving sensitivity was partial corporeal reduction with preservation of the innervation of the glans, however, sensitivity in individual cases was sometimes affected. We also analyzed if reoperation (n = 12) affected the sensitivity, but this could not be shown.
In six cases, the women described that they had never achieved orgasm. Two of these women were clitoris amputated, three were partially resected (once or twice), and the remaining one was not operated. These women displayed individually a diminished sensitivity in the clitoris region. Overall, CAH women (whether operated or not, whether younger or older age group) did not differ from controls in the ability to achieve orgasm (Tables 2 and 3).
Vaginoplasties
The 41 vaginoplasties were either performed as a simple cleavage (n = 24), a dorsal flap (n = 10), or a combination of techniques. There were 12 who were reoperated on in puberty, 20 were primarily operated on in early childhood, and seven had their first operation at puberty, resulting in reoperation in 12 of 32 (37.5%). Cleavage was performed as a single operative procedure in 11 of the 24 cases. No "pull-through" procedures were done. However, cutaneous (n = 1) and intestinal vaginas (n = 1) were performed in two cases.
CAH women and controls had a different impression of the size of the vagina, which was not correlated to the surgical method (Table 4). The introitus of vagina was most often regarded as too small or tight (45.6%) by CAH women, whereas none in the control group had that impression. There were 14 women that reported that they had used a dilator periodically, with good results in all but two. The gynecological examination confirmed vaginal stenosis in five cases, three of them were operated with the cleavage method. In all cases the vaginal depth was normal. Altogether, 20 of 34 CAH patients that had been operated on regarded their vagina as too tight, but also five of the 21 nonoperated. More complaints were registered in patients operated with the cleavage method than in patients operated with other techniques (Table 4). There was a tendency of less frequent usage of tampons in the CAH group, as would be expected. Seven women that did not use tampons were in five cases operated with a flap vaginoplasty.
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). Vaginal discharge and smelling were not a problem unless there was a fistula. There was no significant difference concerning the function of vagina regarding the ability of penetration of an erect penis or a finger. This was not possible for six and three women, respectively, and stenosis was confirmed at gynecological examination in five patients. The lubrication during sexual arousal is normal compared with controls. However, in the few cases (n = 4) of decreased lubrication, three were operated with the flap method. Sensitivity at the sides of the vagina was also diminished after surgery. In general, women with CAH were less satisfied with their vagina compared with controls but not correlated to surgical procedure or older or younger age group (Table 4 and Fig. 2).
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Cosmetic appearance
The women were satisfied with the external appearance of the labia majora, but in four cases the labia were described as thin, and in five cases as "scrotal-like." In 46 cases, we have documented the external genitalia with photographs and judged the photographs anonymously according to a five-point scale. The female gynecologist, male endocrinologist, and two female pediatric surgeons gave a mean validation of 2.0, 3.0, and 3.3 points, respectively. The highest scores were given in the nonoperated group. The cosmetic appearance was not as anatomically satisfactory when examined in a gynecological position due to unsatisfactory size and location of clitoris, as well as scarred tissue, and this differed according to surgical procedure.
Results from self-report questionnaires on quality of life and psychosexuality
Of CAH women, 45% were married or living in a heterosexual relationship as opposed to 68% of controls. There were 39% that had no steady relationship compared with only 18% of controls (P = 0.03, McNemar test). In the CAH group, slightly less persons were engaged in caring professions like nursing and slightly more persons were engaged in blue collar work. Altogether, the socioeconomic status and education level are relatively homogenous in this group as well as in Sweden as a whole.
Half of the CAH women state that the disorder had affected their sex life. The age of menarche did not differ from controls, unless type of mutation was considered (later age of menarche in the more severe mutations). A larger proportion of CAH women had never been pregnant (74%), had no children (76%), or had fewer children compared with controls (36 and 50%, respectively; Table 5), and was comparable to other studies (22, 23). The sexual debut (in 50 of 59 answers) occurred later in life, especially in women older than 30 yr. These differences were even more pronounced when compared with severity of mutation, as indicated in Table 5. The sexual debut also had a tendency to be postponed if surgery had been performed, although not significantly. Heterosexuality was recorded in 41 of 52 (80%) CAH women compared with 60 of 61 (98%) controls (P < 0.005, marginal homogeneity test) compared with 97.6% in a recent national survey in Sweden. The experience of medical checkups was regarded as "mostly positive," and that did not differ concerning type of surgical procedure. Most CAH women preferred early timing of surgery (n = 20), whereas some also advocated surgery at puberty when proper information can be given (n = 9). According to the CAH women, the information about CAH has mainly been focused on the lifelong medication, and many would have appreciated an information leaflet on gynecological, surgical, and psychosexual issues.
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Discussion |
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Surgery
This study of CAH women represents a follow-up of surgery, performed during four decades in Sweden, by many surgeons in different departments. We sometimes had difficulties interpreting the operative procedure from the charts because it was not always clearly described. During the years after the surgery of these CAH women, other surgical procedures have been introduced, such as the Passerini-Glazel procedure (24) and total/partial urogenital mobilization (15, 25, 26), and these novel procedures have also been subject to shorter follow-up studies. In addition, a better understanding of the genetic background of sex development, improved diagnostics, and these better surgical techniques has changed indications and timing of surgery (27). Still, some lessons can be learned from studying patients in a longer lifetime perspective.
The goal with clitoroplasty is to achieve normal size of the clitoris and a good function in adulthood. All women in the control group considered that they have a normal-sized clitoris, which is in contrast with the nonoperated women with CAH, who in almost half of the cases considered the clitoris too large. Furthermore, among the operated women, less than 60% were satisfied with the size of their clitoris, and the rest considered the clitoris either too small or too large. We observed differences in the sensitivity for light touch of the clitoris and a risk of diminished sensitivity after surgery. The importance of sparing the dorsal nerves is evident by preserved sensitivity, especially the dorsal region, even after amputation of the clitoris, as was pointed out by Schober et al. (28). Most women regarded the clitoris as "important for lust," but women that had the clitoris amputated or reoperated on were not of that opinion. There was no significant difference in the ability to have achieved orgasm, but five of the six CAH women, who could not have orgasm, had the clitoris operated. This is not as devastating as described earlier when surgery resulted in an inability to achieve orgasm in 39% after surgery (12). However, our results indicate that the sensitivity of the genital region may be compromised by surgery. Thus, our data confirm that feminizing surgery should be restrictive and calls for specialization of the surgeons that are to perform this type of surgery (9).
The rate of redo vaginoplasty varies in different studies between 12 and 89% (5, 6, 7, 8, 29). In our study 37.5% were reoperated due to vaginal stenosis, and an additional 14 women had used a dilator. None of the control women regarded their vagina as tight/small in comparison to half of the CAH women, thus indicating that treatment often has to be repeated until a good function is achieved, as pointed out by Azziz et al. (29). The minor differences in the result with different surgical methods most probably reflect a more severe malformation from the start and would nowadays be operated with other methods. Painful intercourse was more common in CAH (15 of 50), but not as common as described by Gastaud et al. (22). In this study the meatus was often located in the vagina, which is not the goal of surgery, and can be avoided with a pull-through technique and urogenital mobilization. However, location of the meatus appeared not to cause any disturbances.
Cosmetic appearance
The cosmetic appearance of the external genitals in a normal standing position was often satisfactory in the CAH women. However, the clitoral region and the labia minora were often characterized by scarred and irregular tissues, in addition to a nonanatomical size and location of clitoris, thus confirming the result by Creighton et al. (7). These problems can be a burden for the women. It was quite common to express a feeling of embarrassment toward sexual partners, which may be a reason for postponing sexual debut. Therefore, this aspect should be treated with respect by pediatric surgeons. Patients should also be informed about the normal appearance of female genitalia (19).
Psychosexual aspects
We have clearly shown that many aspects of quality of life are affected by CAH, such as sexual debut, fertility, partnership, and sexual relationships as was also shown in recent studies (30, 31). The incidence of homosexuality and bisexuality is significantly higher than in controls, which is consistent with a study by Dittman et al. (32) and a recent study by Gastaud et al. (22). These results suggest that bisexuality and homosexuality may have a biological background and that there is a need for continuous psychological support during upbringing.
Conclusions
The overall quality of adult life in women with CAH is affected both by the type of mutation as well as the operative procedure in itself. Whether operated or not, the CAH women were often less satisfied with the genital function and appearance. Indications for surgery should be restrictive given the risk for diminished sensitivity of the clitoris. Given the results from this study and having met these women, we, as others before us, strongly argue that the medical, surgical, and psychological treatment be centralized to specialized teams.
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Acknowledgments |
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Footnotes |
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Disclosure Summary: The authors have nothing to declare.
First Published Online November 20, 2007
Abbreviations: CAH, Congenital adrenal hyperplasia; NC, nonclassical; SV, simple virilizing; SW, salt-wasting.
Received March 12, 2007.
Accepted November 8, 2007.
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