The lecture has been given on Oct. 11th & 13th, 2010 by Dr. Hanaa.

1. Gynaecological disorders of childhood andadolescence

2. Gynaecological problems in the prepubertal child and at adolescence create great levels of anxiety in parents particularly, but fortunately very few of these disorders could be considered common. However, when they do present it is important that the clinician has an understanding so that appropriate advice may be given to the patient andmanagement is frequently through simple means. The disorders fall into two groups, those related to prepuberty and those of adolescence.

3. Prepubertal child Vulvovaginitis This is the only gynaecological disorder of childhood which can be thought of as common. Its aetiology is based on opportunistic bacteria colonizing the lower vagina and inducing an inflammatory response. The lack of labial protection and the close apposition of the anus mean that the vulva and lower vagina are constantly exposed to faecal bacterial contamination. The hypo-oestrogenic state in the vagina means that there are no lactobacilli and therefore the vagina has a resulting pH of 7 making it an ideal culture medium for low virulent organisms.

4. Table.1 Causes of vulvovaginitis in children Bacterial Non-specific – common Specific – rare Fungal – rare Candida of vulva only Viral — rare Dermatitis Atopic Lichen sclerosis Contact Sexual abuse Enuresis Foreign body

5. The causes of vulvovaginitis in children are shown in Table .1 The vast majority of cases are due to nonspecific bacterial contamination, although the other causes should be remembered. Candidal infection in children is extremely rare, although because it is a common cause of vulvovaginitis in the adult it is a common misdiagnosis in children. Candida in children is usually associated with diabetes mellitus or immunodeficiency and almost entirely related to these two medical disorders. The presence of viral infections, for example, herpes simplex or condylomaacuminata, should alert the clinician to the possibility of sexual abuse. Vulval skin disease is not uncommon in children, particularly atopic dermatitis in those children who also have eczema. Referral to a dermatologist is appropriate in these circumstances. Lichen sclerosis is also seen in children and may cause persistent vulval itching. The skin undergoes atrophy and fissuring and is very susceptible to secondary infection.

6. Sexual abuse in children may present with vaginal discharge. Any child who has recurrent attacks of vaginal discharge should alert the clinician to this possibility. However, as non-specific bacterial infection is a common problem in children the clinician must proceed with considerable caution in raising the possibility of sexual abuse. Only those bacterial infections related to venereal disease for example, gonorrhoe, may be cited as diagnostic of sexual abuse.

7. It is important that the clinician remembers that many girls suffer from urinary incontinence, particularly at night, and this creation of a moist vulva allows secondary irritation by bacteria leading to vulvovaginitis. DIAGNOSTIC PROCEDURES There are two aspects of the diagnosis in this condition in children. The first is inspection of the vulva and vagina. It is imperative that the clinician has good illumination, particularly if there is a history of the possibility of a foreign body being in the vagina. It is usually possible to examine the vagina through the hymen using an otoscope. This may well allow the diagnosis of a foreign body to be made.

8. The second aspect of diagnosis involves the taking of bacteriological specimens. This can be extremely difficult in a small child, as it is unlikely that the child will be cooperative. The best way to take a bacteriological specimen is to use a pipette. The pipette allows 1–2 ml of normal saline to be expelled into the lower part of the vagina, the tip of the pipette having been passed through the hymenal orifice. The fluid is then aspirated and sent for bacteriology. If a diagnosis of pin worms is to be excluded, then a piece of sticky tape over the anus early in the morning before the child gets out of bed will reveal the presence of eggs on microscopy.

9. Treatment The vast majority of children do not have a pathological organism. The primary treatment in this group is advice about perineal hygiene. The child must be taught to clean her vulva, particularly after defaecation from front to back, as this avoids the transfer of enterobacteria to the vulval area. After micturition the mother and child should be instructed to clean the vulva completely and not to leave the vulval skin wet as this damp, warm environment is an ideal culture surface for bacteria that cause vulvovaginitis. Excessive washing of the vulva must be avoided as this leads to recurrent exfoliation and vulval dermatitis. During acute attacks of non-specific recurrent vulvovaginitis, children often complain of burning during micturition due to the passage of urine across the inflamed vulva. The use of barrier creams in these circumstances may be very useful.

10. Labial adhesions Labial adhesions are usually an innocent finding and a trivial problem, but its importance is that it is frequently misdiagnosed as congenital absence of the vagina. The physical signs of labial adhesions are easily recognized. In the post delivery hypo-oestrogenic state the labia minora stick together in the midline, usually from posterior forwards until only a small opening is left anteriorly through which urine is passed. Similar adhesions sometimes bind down the clitoris. It may be difficult to distinguish the opening at all. The vulva has the appearance of being flat, and there are no normal tissues beyond the clitoris evident. .

11. There are usually no symptoms associated with this condition, although older children may complain that there is some spraying when they pass urine. The aetiology of the hypo-oestrogenic state means that they are never seen at birth, and instead occur during early childhood. As late childhood ensues and ovarian activity begins there is spontaneous resolution of the problem. In the majority of cases no treatment is required and the parents should be reassured that their daughters are entirely normal. In those children in whom there are some clinical problems local oestrogen cream can be applied for about 2 weeks

12. In some rare circumstances this will not resolve the problem, but at the end of the oestrogen therapy the midline is so thin that gentle separation of the labia may be undertaken using a probe, and this procedure causes no discomfort to the child. Application of a bland barrier cream at this stage will prevent further adhesion formation. Finally, in taking a history it is important to establish that there has not been any trauma to the vulva as very rarely labial adhesions may be the result of sexual abuse.

13. Puberty Puberty is defined as the period of time during which secondary sexual characteristic develop menstruation begins and the psychological outlook of the girl changes as she develops a more adult aspect to herself. The end result of puberty is the establishment of the fully physically mature adult woman capable of reproductive performance and fully psychologically developed as an adult.

14. There is some form of hypothalamic trigger which leads to pulsatile release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) between 5 and 10years of age, with ovarian release of oestrogen usually from the age of 8.This oestrogen mediates the pubertal changes. The sequence starts with a somatic growth spurt followed bybreast development, then development of pubic hair followed by axillary hair and finally the menarche [first periodBreast development, pubic hair and axillary hair development are classified by the Tanner system into five stages.

15. Normal puberty Growth spurt The somatic growth spurt is the first notable change due to oestrogen stimulation. After the menarche somatic growth will continue for approximately 2 years until fusion of the epiphyses, after which no further growth is possible. Precocious puberty may lead to premature epiphyseal closure and the child may fail to attain its full height potential

18. Hair growth Pubic hair precedes axillary hair development and also shows four stages. Initially there is sparse hair on the labia; this then grows centrally and advances onto the mons pubis. The next stage is for the hair to spread laterally a little, with the full adult triangular distribution as the final stage.

20. Menarche The first menstrual period is the final stage in pubertal development, and occurs in 95% of girls between the ages of 11 and 15 years. The average age of the menarche in the UK is 13 years, a fall in the age of menarche being noted in children in developed countries. This is thought to be a reflection of improved nutritional status - some researchers believing that a critical body weight must be reached before menarche is achieved. This theory has some merit as it is noted that moderately obese girls have an earlier menarche than those of more normal weight. Conversely, girls with anorexia or adhering to an intensive exercise programme may show delay in the age of menarche.

21. There is no doubt that this is genetically controlled, and the release of gonadotrophin-releasing hormone (GnRH) by the neurones in the arcuate nucleus of the hypothalamus is controlled by central factors influencing DNA within the cells Early menstrual cycles are in the majority anovulatory,and cycle length may vary for some considerable years after menarche. It may take some 5–8 years before menstrual cycle normality is established.

22. Abnormalities of puberty Precocious puberty Precocious puberty is defined as the onset of secondary sexual characteristics prior to the age of 8 years. The aetiology of this is varied. In the vast majority of girls the cause is unknown. This idiopathic group constitutes 95% of all cases of precocious puberty. It is likely that this is solely due to initiation of the normal process of puberty at a premature age. The onset is genetically predetermined. If this genetic determinant is inappropriately timed then the normal process of puberty will occur whenever the initiation occurs.

23. Some children with neurological disorders like cerebral tumours, hydrocephalus or postmeningitis or encephalitis may have an early puberty due to activation of the hypothalamus by the disease process. The mechanism by which this occurs remains obscure; although in the McCune-Albright syndrome, which is a disorder involving cystic bony change (polyostotic fibrous dysplasia), there is also associated endocrine dysfunction particularly of the hypothalamus and pituitary and in this condition precocious puberty is common.

24. Various ovarian and adrenal tumours may be hormone secreting thus inducing secondary sexual characteristic changes, but these are not truly pubertal and are reversible on removal of the tumour. Cases of ingestion of exogenous oestrogen by children have also been reported, and this will indeed result in the onset of some menstrual loss in some children and again must not be considered as true precocious puberty

25. TREATMENT In those cases of idiopathic precocious puberty the clinician is faced with the problem of reversing the normal onset of puberty. There can be little doubt that the treatment of choice is the use of GnRH analogues, which are extremely effective at obliterating follicle-stimulating hormone (FSH) production by the pituitary. By doing this, the prepubertal state is re-established and the child can remain on this therapy until aged about 11.5–12 years when the therapy can be withdrawn and the normal onset of puberty will ensue.

26. Any breast or pubic hair development that has occurred prior to the diagnosis will usually be reversible as the hypo-oestrogenic state prevents further growth and in most cases this results in some resolution of early change. However, if the secondary sexual characteristic changes have been much greater and development is beyond Tanner stage 3, little effect can be expected by this therapy on the physical changes. Similar success can be achieved with those children with neurological problems. Children who are found to have ovarian or adrenal tumours or gonadotrophin-secreting tumours should be treated surgically and their problems will resolve

27. . It is important for the gynaecologist who is presented with these problems to remember that precocious puberty is socially undesirable and social management of the case is essential. Very rarely would a gynaecologist opt to treat a child with precocious puberty without the help of a paediatrician. In fact, cases of precocious puberty are now usually managed medically by paediatric endocrinologists.

28. Adolescence The adolescent gynaecological patient usually presents with one of three disorders. First, there are those problems associated with the menstrual cycle and menstrual dysfunction, dysmenorrhoea and premenstrual syndrome are the main group of disorders. Second, the patient may present with primary amenorrhoea and third, is the problem of teenage hirsutism.

29. Heavy menstruation Normal menstrual loss should not exceed 80 ml during a period, although in 5% of individuals it is heavier than this and causes no trouble The clinician is faced in these circumstances with attempting to assess whether or not the child truly has menstrual loss that is serious as a medical condition or menstrual loss that is irritating and distressing without being medically harmful. The best way to establish which of these is the case is to measure the haemoglobin. If the haemoglobin level is normal, that is, greater than 12 g/l, then an explanation should be given to the mother and child of the normal physiology of menstrual establishment that the manifestation of the menstrual loss is normal and that it may take some time for the cycle to be established.

30. This condition requires no active treatment. However, it is imperative that the child is followed up at 6-monthly intervals until the pattern of menstruation is established as reassurance is the most important part of the management process of these girls In those girls with haemoglobin levels between 10 and 12 g/l it is apparent that they are losing more blood at menstruation than is desirable. Again, an explanation is required so that the mother and daughter understand the cause of the problem and the child should be administered iron therapy to correct what will be mild iron deficiency anaemia.

31. In terms of management, menstrual loss needs to be reduced and this may be achieved by using either progestogens cyclically for 21 days in every 28-day cycle or to use the combined oral contraceptive pill. Finally, in the child with a haemoglobin count of less than 10 g/l, it is obvious that serious anaemia has resulted from menstrual loss. This again requires an explanation but more urgent attention from a medical point of view. Progestogens are very much less likely to be effective in this group and the oral contraceptive pill is by far the treatment of choice. It may be given continuously for a short period of time so that the anaemia can be corrected using oral iron and then the pill may be used in the normal way so that menstrual loss occurs monthly, if desired.

32. Primary dysmenorrhoea Primary dysmenorrhoea is defined as pain which begins in association with menstrual bleeding. The management of dysmenorrhoea in the teenager is no different from that of the adult . Both the use of non-steroidal anti-inflammatories and the oral contraceptive pill is pertinent in teenagers, but again failure of these medications to control dysmenorrhoea should alert the clinician to the possibility of uterine anomaly and ultrasound imaging of the uterus should be performed to establish whether or not an anomaly exists.

33. Premenstrual syndrome This is a difficult problem in adolescence as the psychological changes that are occurring during this time of a woman’s life are often complex and stressful. It is established that premenstrual syndrome is a stress-related disorder. Therefore in teenage girls undergoing puberty the stresses and emotional turbulence that are associated with this, not surprisingly, may lead to premenstrual problems. These are very difficult to manage and are usually not medically treated but addressed through the help of psychologists if reassurance from the gynaecologist and an understanding of the process to the mother is not successful

34. Hirsutism Table.3 Causes of hirsutisminadolescents Androgenic causes Congenital adrenal hyperplasia • Classic • Late onset Androgen-secreting tumours Polycystic ovarian syndrome Idiopathic XY gonadaldysgenesis

35. Treatments for hirsutism are as in the adult . In adolescence the mainstay of androgen excess treatment has been the oral contraceptive pill and without doubt this remains the main form of treatment. As the majority of these girls have some ovarian dysfunction, be that polycystic ovarian syndrome or an undefined problem, suppression of ovarian activity is very effective at circulating androgen. If this is insufficient to gain control of hair growth, then the use of cyproterone acetate or spironolactone may be considered.

36. Delayed puberty Delayed puberty (Table 2) is rare with only 1% of females not having had menarche by the age of 18. If there are no secondaiy sexual characteristics by the age of 14 delay is diagnosed and investigation is appropriate. The largest group are those with ovarian failure, more than half of whom have chromosomal anomalies. Causes of delayed puberty Cause Percentage Underlying cause Hypergonadotropichypogonadism 43% Gonadaldysgenesis,e.g. T Turner's syndrome Hypogonadotropichypogonadism 31% Constitutional, chronic m medical illness,anorexia Eugonadism 26% Abnormal genitalia, e.g. A absent uterus, vaginal septum

37. In girls with hypergonadotropichypogonadism the ovarian failure may be associated with an abnormal karyotype, particularly Turner's syndrome. In those with abnormal karyotype it may be that there is gonadaldysgenesis (the external genitalia are usually of infantile female type) or the resistant ovary syndrome with normal appearance of external genitalia (where the ovary fails to respond to the increased levels of LH and FSH) but where there can be spontaneous ovulation and obviously pregnancy can thus occur, though prognosis with respect to future pregnancy in these cases should be guarded.

38. With hypogonadotropichypogonadism (low levels of LH and FSH) the delay may be constitutional - particularly when short compared to her family but appropriate for the stage of puberty and bone age - or due to a chronic medical condition or anorexia nervosa. In the eugonadotropic group (normal LH and FSH) congenital absence of the uterus (Rokitansky syndrome) or vaginal developmental obstruction should be considered.

39. Treatment of delayed puberty Initial management First exclude pregnancy Ask about chronic illnesses, anorexia, excessive physical exercise or family history of delayed puberty. Heart problems may be found with chromosomal disorders, urinary or bowel disorders with anatomical disorders of the genital tract, hernia repairs may suggest gonadal disorder and slow general development is associated with hypothyroidism. Examination should include measurement of height, weight and visual fields; check for secondary sexual characteristics, virilization and hirsutism. Vaginal examination is inappropriate unless the girl is sexually active. Check for stigmata of Turner's syndrome (short stature, webbed neck, and wide carrying angle).

40. Investigations include sending serum for LH and FSH (low with constitutional delay), testosterone (increased in polycystic ovarian syndrome), TSH (increased in primary hypothyroidism) and prolactin (ideally measured under nonstressed conditions). Karyotype is needed if a chromosomal problem is suspected; if an XY chromosomal pattern is found, it is usual to suggest gonadectomy due to the 25% risk of tumour in the gonad. X-ray for bone age would confirm constitutional delay. Assessment of 17-hydroxyprogesterone when congenital adrenal hyperplasia is suspected, pelvic ultrasound to assess pelvic anatomy and skull X-ray if prolactin is raised are appropriate.

41. Causes and further management Normal secondary sexual characteristics but with primary amenorrhoea. This is most commonly caused by an imperforate hymen and is characterized by cyclical pain and a haematocolpos...

42. Poor or absent secondary sexual characteristics. These comprise: 1-Constitutional delay The diagnosis is likely in a healthy adolescent who is short for the family but appropriate for the stage of puberty and bone age. There is often a family history and it may be associated with chronic systemic disease (rare, but consider hypothyroidism and malabsorption). If the bone age on X-ray is less than the chronological age than it is reasonable to adopt a conservative approach. Anorexia nervosa should also be considered

43. 2. Ovarian dysfunction. This may be due to gonadal agenesis with Turner's syndrome or Turner's mosaic. Treatment is specialized as oestrogen treatment may predispose to short stature by premature epiphyseal closure. Therapy is with low-dose ethinylestradiol initially, increasing over the next 18 months. A progestogen is then added for 5 days every 4 weeks. The dose of oestrogen is increased if response is adequate and the contraceptive pill substituted.

44. 3. Hypothalamopituitai-y disorders. Hypogonadotropichypogonadismis usually associated with pituitary tumoursand other pituitary deficiencies. In Kallmannsyndrome there is a congenital deficiency of luteinizing hormone-releasing hormone (LHRH) and absent olfactory sensation.