Controversies on clitoroplasty

Abstract

A review of the literature regarding the current state of knowledge of the anatomic and physiologic features of the female clitoris was conducted. Based on this evaluation, operations on the clitoris were reviewed. The anatomic and physiologic reconstruction problems of surgical techniques for female pseudohermaphroditism that have previously been reported were reviewed. The author suggests that clitoroplasty is essential for patients with ambiguous genitalia, but the decision regarding the correct procedure, taking into account anatomic and physiologic success, can be controversial. This may be because of unclear anatomic and physiologic definitions, even for healthy people. As a temporary solution, more conservative procedures for maximally effective treatment are suggested.

Introduction

Worldwide, one in 2000 infants is diagnosed with genital ambiguity each year [Yang et al. 2007]. Ambiguous genitalia represent one of the major challenges for physicians and surgeons [Sircili et al. 2006]. The treatment is multidisciplinary, and coordination of neonatology, pediatric endocrinology, and pediatric surgery is essential for an acceptable treatment [Gollu et al. 2007]. Other disciplines must also be involved in the decision and progression. Ambiguity mostly occurs due to female pseudohermaphroditism. Thus, most of the treatments are for female genital structure.

Unfortunately, there are some major problems for genitalia operations, especially for the masculinized clitoris [Yang et al. 2007]. It is known that clitorectomy had been used widely in the 1930s and 1950s, at which time it was still reported that the clitoris was not important for female sexual maturation [Fonkalsrud et al. 1977]. In the 1960s, Lattimer and colleagues introduced clitoroplasty as a new approach for clitoromegaly [Lattimer et al. 1961], and clitorectomy has been abandoned in the modern era. Although there has been definite progress in understanding the anatomy and physiology of the clitoris, knowledge of the measurement of physiologic parameters of sexual function in women is still lacking, and far behind that in men [Woodard and Diamond, 2009]. Also, as a baseline problem, female urogenital anatomy is understood inadequately and is not even described sufficiently in most anatomical textbooks [Lean et al. 2007]. Another problem is the undesired effects that patients experience after urogenital reconstruction [Lean et al. 2007]. In addition, achieving hormonal stability has to be worked on for the normal life period, but the long, time-consuming follow-up procedures make it difficult to evaluate surgical efficacies and the hormonal course of patients [Yang et al. 2007].

Based on these considerations, the gaps in our knowledge are discussed in this review. This criticism may be helpful as a basis for work on those areas that are poorly understood, and may strengthen the practical effects of the procedures.

Clitoris anatomy and physiology

The clitoris is the erectile part of the external genitalia; it has homologous properties with the penis [Williams et al. 1989]. The major difference between female external genitalia and male genitalia is that female genitalia are separate from the urethra [Williams et al. 1989]. The corpus clitoridis has two corpora cavernosa with erect ile tissue surrounded by dense fibrous tissue around each corpora [Williams et al. 1989]. These corpora are separated incompletely from each other with a medial located by a fibrous pectiniform septum. Each crus clitoridis is attached to the corresponding ischial ramus [Williams et al. 1989].

Details of the female genitalia gross anatomy and histology are described in various reports in the literature. Schober and colleagues evaluated internal portions of the clitoris using cadaveric materials [Schober et al. 2004]. Using magnetic resonance imaging (MRI), O’Connell and colleagues demonstrated the urethra, bulbs, crura, and corpora forming the root of the clitoris, and the relationship between them [O’Connell et al. 2005]. The corpora cavernosa of women have been shown by MRI using a fat saturation technique [O’Connell et al. 2005]. Using that technique, it was revealed that all the clitoral structures, from the crus to glans clitoridis, were colored bright white; thus, it can be said that the whole clitoris is erectile. It was also revealed that the clitoris is highly vascular, even under conditions of nonarousal [O’Connell et al. 2005]. This fact is important because studies have shown that some of the functions like erotic stimulation of clitoris are useful for female characteristics [Fonkalsrud et al. 1977].

Histological evaluation of the clitoris, especially of the corpora cavernosa, is incomplete because for many years the clitoris was considered a rudimentary and nonfunctional organ [Toesca et al. 1996]. Baskin and colleagues evaluated the masculinized clitoris after dissection and put the serial dissected specimens together using imaging software after Massion chrome staining. They revealed that the nerves of the clitoris surrounded the whole corpus [Baskin et al. 1999].

In spite of the accumulating data, there are still controversies regarding some histological evaluations of the clitoris. For instance, it is known that the subalbugineal layer between the erectile tissue and tunica albuginea is absent in the clitoris, but desmin and vimentin immunoreactivity evaluations in arterial and vein muscle cells of the clitoris are not clear from previous reports [Toesca et al. 1996].

External genitalia formation continues for life, and hormone-dependent development like sexual dimorphic development of the external genitalia is the main reason in the adulthood period [Yamada et al. 2006]. Androgens are important for the development of the penis and clitoris. Androgens are the precursors of estrogens and are also important for the development of reproductive functions in a hormonal homeostasis [Johnson and Berman, 2005]. Androgens may also have effects on female sexual functions, although further studies are needed to understand it comprehensively [Yamada et al. 2006; Johnson and Berman, 2005]. O’Connell and Delancey have recently studied the androgenic and estrogenic activities of the corpus cavernosum cells [O’Connell and Delancey, 2005]. However, there is still a lack of information on the responses of the tissue and the regulatory mechanisms of the organ. This may be because of insufficient human tissue evaluation. Nevertheless, materials can be obtained from transsexual patients, and it has been shown in the tissues of transsexuals that estrogen receptors increase following hormone replacement therapy [Schultheiss et al. 2003]. This is explained as upregulation or an epiphenomenon of ligand-receptor binding. In an experimental study, estradiol interfered with cell proliferation during fetal cavernosal smooth cell culture incubations, but testosterone acted in the opposite way [Schultheiss et al. 2003]. Despite these studies, to our knowledge, there has not been a hormone-related study evaluating the various formations of sexual development in ambiguous patients, particularly with respect to enzyme deficiencies. No developmental gene function has been defined in the later developmental periods for female genitalia, labia, and clitoris [Copcu et al. 2004].

Clitoromegaly

Some of the reasons for clitoromegaly are nonhormonal conditions, pseudoclitoromegaly, and idiopathic clitoromegaly [Copcu et al. 2004]. However, prenatal androgen exposure because of adrenal dysfunction or a related enzyme defect is the main reason for clitoromegaly [Yamada et al. 2006]. For isolated clitoral hypertrophy, female pseudohermaphroditism differs from external genitalia masculinization due to congenital adrenal hyperplasia. Masculinization of the external genitalia to varying degrees occurs if hyperandrogenism is seen before 12 weeks of gestation, although after the twelfth week it only results in a single, isolated clitoromegaly. Female pseudohermaphroditism is most frequently seen secondary to congenital adrenal hyperplasia (CAH) or adrenogenital syndrome [Copcu et al. 2004]. CAH is mostly observed with 21-hydroxylase deficiency, and various degrees of masculinization of the external genitalia are present in this deficiency [Yang et al. 2007; Gastaud et al. 2007]. Practically, it can be supposed that suppressive glucocorticoids can influence the deficient cascades of hormone formations, but postnatal overload of adrenal androgens and their effects cannot usually be stopped [Gastaud et al. 2007]. In contrast to this report, Fonkalsrud and colleagues reported that early recognition of clitoromegaly may possibly prevent postnatal virilization [Fonkalsrud et al. 1977]. Estrogen replacement therapy is used for some conditions, such as the menopause, but to the author’s knowledge, replacement indications for diseases causing clitoromegaly are unclear. It is known that high oral doses of estrogen to replace the absent hormone cause liver synthesis of sex hormone-binding globulin, which binds testosterone strongly and so causes low bioavailability [Johnson and Berman, 2005]. Oral estrogen also decreases the bioavailability of adrenal androgens [Johnson and Berman, 2005]. In spite of these data, it is not known if replacement therapy is useful for interrupting clitoromegaly or if it can reduce the degree of hypertrophic clitoris.

Clitoroplasty

Females with adrenogenital syndrome are the largest group requiring surgical genital correction [Zaparackaitė et al. 2002]. The main expectations for the operations are to create a normal female anatomy, with minimal complications and improvement of life quality [Zaparackaitė et al. 2002]. Cosmesis, structural integrity, and coital capacity of the vagina, and absence of pain during sexual activity are the parameters to be judged by the surgeon [Schober et al. 2004]. Although expectations can be standardized within these few parameters, operative techniques have not yet become homogeneous [Lean et al. 2007]. Investigators have preferred different operations for different ages of patients [Lean et al. 2007].

In contemporary estimation, gender assessment and surgical treatment are the two main steps in intersex operations [Akbiyik et al. 2010]. The first treatments for clitoromegaly were simply resection of the clitoris [Yang et al. 2007]. Later, it was understood that the clitoris glans and sensory input are important to facilitate orgasm [Sircili et al. 2006]. The epithelium of the glans clitoridis has high cutaneous sensitivity, which is important in sexual responses [Williams et al. 1989]. Therefore, recession clitoroplasty was later devised as an alternative, but reduction clitoroplasty is the method currently performed [Yang et al. 2007]. In this operation the glans is preserved and parts of the erectile bodies are excised. The development of reduction clitoroplasty took more than 50 years, but there are still problems with the technique, including loss of sensation, sexual function, and slughing of the glans [Yang et al. 2007; Lean et al. 2007].

Imbricating and burying the glans clitoris preserves the organ with its innervations and function, although pain during stimulus because of trapped tissue under the scarring is nearly routine [Yang et al. 2007]. In another method, 50% of the ventral clitoris is removed through the level base of the clitoral shaft, and it is reported that good sensation and clitoral function are observed in follow up. However, it has also been reported that the complications are from the same as those in the older procedures for this method [Yang et al. 2007].

Accurate assessment parameters for sexual function are not easy to identify during the long follow up and healing process for anatomic and cosmetic appearance [Lean et al. 2007]. Gollu and colleagues have reported that dissatisfaction has been growing regarding surgical outcome [Gollu et al. 2007]. Dissatisfaction is also an unclear entity and measurement of this entity is not easy. Schober and colleagues evaluated the considerations of clitoris size of women and experts in their study [Schober et al. 2004]. According to women, a clitoris of only two-fifths size is normal compared with the experts’ normal size judgments. As a functional outcome, erotic sensation has to be evaluated for effective operations, but for this parameter, only women’s evaluations are meaningful. Consequently, it is difficult to employ as an outcome in childhood. Parallel to all these unclear assessments, patients have criticized feminizing genitoplasty harshly in recent years as sexual functioning is not sufficient, and some activists even advocate stopping the operations until more information has been obtained [Schober et al. 2004]. This is one of the most important controversies with respect to performing more reduction clitoroplasty operations.

Zaparackaitė et al. [2002] presented the new viewpoint that clitoral reduction is not needed because of insufficient data on the psychological and functional effects in comparative to conservative treatments for clitoroplasty. Therefore, recession clitoroplasty is still discussed for the preservation of clitoral sensation without resection [Rajendran and Hariharan, 1995].

As a therapeutic part of the intersex diseases, medical endocrine management cannot be underestimated. However, knowledge of the efficacy of medical endocrine management, especially for long-term outcomes, is limited [Lean et al. 2007].

All these reasons remind us that an incomplete or insufficient definition of the anatomic and physiologic structure of female genitalia is the main treatment problem. Female anatomy is not presented completely, even in anatomy books, and the hormonal activity of the clitoris and cavernous body is not totally understood. For situations such as female genitalia diseases, it is best to perform more conservative procedures rather than take radical steps or perform cosmetic arrangements. The author believes that discovering ‘how it works’ must be the step to be performed, which means few modifications of tissues until complete anatomic and physiologic elucidation is complete. Consequently, recession clitoroplasty may be used or modified for better results that salvage clitoral tissue for future technologies and treatments. Sliding the clitoral body and corpus through the inferior region of the ischiopubic ramus by dividing two-thirds of the corpora cavernosa and fixing them within pubic soft tissue may be tried as a recession process. The whole erectile tissue with its sensory properties may be saved in this way.

It can also be proposed that performing operations will not be enough for these patients. Evaluation of hormonal use for therapeutic reasons has to be developed. To the author’s knowledge, the literature discussing hormonal development projection, particularly from the prepubertal to pubertal period is very limited at present. Hormonal activity identification and efficient hormonal replacements before and/or during the process may help in controlling the male gender characterization of these organs. Local hormonal therapy aiming for genitalia maintenance may also be an area of interest.

Conclusion

There is scope for discussion of new therapeutic options in this area. In the author’s opinion, the gaps in the knowledge of the disease must be filled in, starting from first principles.