Introduction

Sex determination, or genetic sex, is a process starting at conception by which the undifferentiated genitalia evolve into male or female reproductive organs. It depends on chromosomal complement and is influenced by endocrine events and by nongenetic and nonendocrine factors such as nutrition, toxins (fetal alcohol syndrome), intrauterine environment (altered uterine blood flow, placental function, local uterine circulation and placental and umbilical circulation).

Initially this cascade of events is dependent on chromosomal or genetic sex, and then appropriate development of the hypothalamic—pituitary—gonadal axis is necessary for sex steroid secretion as well as for oogenesis and ovulation in the female and spermatogenesis in the male.

Genotype and phenotype

Genetic sex directs the embryonic gonad to differentiate into either testis or ovary and is determined by the presence or the absence of the Y chromosome.

The sex-determining region of the Y chromosome (SRY) has been mapped to the tip of the Y chromosome (Parker et al., 1999) and has been shown to be necessary and sufficient to initiate the male differentiation pathway and acts as a genetic switch towards testis development. If it is absent (or delayed in expression), ovarian differentiation occurs. However, many other factors involved in sex differentiation have been identified and are located on autosomal genes. In the presence of “male differentiating signals”, testosterone and Müllerian inhibiting factor (anti-Müllerian hormone (AMH) or Müllerian inhibiting substance) are secreted by the fetal gonads. Testosterone is converted to dihydrotestosterone by the 5α-reductase enzyme in target tissues.

The management of intersex conditions and anomalies of the development of the female genitalia can only be properly achieved with appropriate input from a number of health professionals. Furthermore, the needs of the individual may change over time and so both the patient and her family must be provided with a seamless transition between the various stages of care — from the diagnosis, which may be in early infancy or in the teenage years, through childhood, adolescence and then to adulthood. Therefore, although intersex conditions are rare, it is imperative that they are managed in centres by a multidisciplinary team that includes paediatric surgeons, urologists (often paediatric and adult), plastic surgeons, endocrinologists, specialist nurses, psychologists and also the gynaecologist. The role of the gynaecologist is to help to coordinate the transition from childhood through adolescence and then womanhood and to help with issues relating to sexual function and sexual identity, endocrinology and fertility. It is during the difficult time of adolescence that the patient usually first realises that there are serious problems and it is often the specialist gynaecologist who helps her to understand the diagnosis and requirements for management. The support of a skilled nurse and clinical psychologist is invaluable at this time.

The Department of Health in the UK is currently reviewing the national provision of services for the management of intersex. Parathentically, those units that have the skills to manage intersex conditions also have the appropriate facilities to treat complex developmental anomalies of the Müllerian tract (for example cervical and vaginal agenesis).