- Email: [email protected]
Adolescent gynaecology
Current Obstetrics & Gynaecology (2002) 12, 150 ^154
c 2002 Elsevier Science Ltd doi:10.1054/cuog.2001.0251 available online at http://www.idealibrary.com on
Adolescent gynaecology D. Keith Edmonds Consultant Obstetrician and Gynaecologist, Queen Charlotte’s Hospital, Du Cane Road, London W12 0HS, UK
KEYWORDS adolescent gynaecology; puberty; primary amenorrhoea; menstrual disturbance; vaginal anomalies; contraception
Summary The transition of a female from childhood to adulthood is a complex process.The control ofthe onsetof pubertyis normally anuneventful sequence of events but disorders may lead to dysfunction in the menstrual cycle or be a symptom of other diseases, such as anorexia nervosa.Failure to establish pubertyneeds treatmentin specialistcentres as does the managementof primary amenorrhoea and the surgical aspects of this problem are referred to in the text.These disorders may be obstructive or due to congenital absence ofthe vagina.This article discusses some ofthe aspects of adolescent gynaecology, whichillustrates the need for a specialistknowledge to manage these cases correctly. & 2002 Elsevier Science Ltd
INTRODUCTION Adolescent gynaecology concerns aspects of developmental and functional defects in addressing the transition from childhood to the fully fertile female. The adolescent is a complex individual undergoing dramatic physiological and anatomical changes and these changes involve complex endocrine interactions with a subsequent anatomical response which will allow reproduction of the species when these processes are complete. Disorders of this process are fortunately uncommon but when they are present, they have a dramatic impact on the individual both physically, emotionally and intellectually and these are most dramatic when there is a failure to be able to ful¢l this reproductive function.
CONTROLOF THE ONSETOF PUBERTY The fetal gonad is identi¢able as an ovary at around 7^ 8 weeks’ gestation and evidence of hypothalamo-pituitary function is demonstrable at around 10 ^12 weeks’ gestation. By16 weeks’ gestation, FSH and LH levels have risen to signi¢cant proportions and by 20 weeks’ gestation the hypothalamo-pituitary ovarian axis is functional. The number of oocytes within the ovary at this gestation is approximately 5.9 million, but subsequent massive atresia, possibly due to a form of apoptosis, means that at birth this oocyte count is reduced to around 2 million. The latter part of pregnancy is associated with placental production of oestriol and rising levels of oestriol pass Correspondence to: DKE.Tel: +44 (0)20 8383 3586; Fax: + 44 (0)20 8383 3419; E-mail: [email protected]
into the fetal circulation causing negative feedback on the hypothalamus, thereby reducing circulating levels of FSH within the fetus.This phenomenon further supports the concept of an intact hypothalamo-pituitary-ovarian axis prior to birth. Following birth the female neonate has its source of oestriol withdrawn when the umbilical cord is severed and inhibition of the hypothalamus ceases leading to elevated levels of FSH, sometimes as high as castrate levels, which remain elevated in the ¢rst 9 months to 1 year following birth. This phenomenon may lead to activation of oocytes within the ovary, although the frequency and amplitude of the pulses of GnRH are chaotic. Oestradiol may well be produced during this ¢rst year of life at su⁄cient levels to induce endometrial growth and occasionally menstrual loss or growth of the breast bud. This important piece of physiology must be remembered when female infants present with these symptoms. By the end of the ¢rst year of life, or at the latest 18 months, gonadotrophins are suppressed and levels of FSH are almost unrecordable throughout childhood. Around age 8 or 9, single pulses of GnRH begin nocturnally at around 04:00 h.Over the ensuing 4 years, increase in nocturnal frequency and amplitude progresses into day-time pulses, which eventually, at around age 12.5 years, results in the establishment of the fully functional hypothalamo-pituitary-ovarian axis, which leads on to menarche and thereafter to co-ordinated ovulatory cycles and reproductive potential. The control mechanism for the down-regulation of FSH after the ¢rst year of life and the re-establishment in late childhood, remains speculative. However, it is more than possible that this may be controlled through the production of leptin, a product of fat cell metabolism. The neurones of the GnRH-producing cell lie in the arcuate nucleus of the hypothalamus. Receptors on the
ADOLESCENT GYNAECOLOGY
cell surface for aspartate and epidermal growth factor are now known to control whether the cell is activated and therefore produces GnRH, or whether it is inactivated, as in the hypogonadotrophic state. It is postulated that the gene for transforming growth factor alpha (TGF-a) may regulate this receptor expression, thereby controlling the production of gonadotrophins.There are animal data to support the concept that leptin may control theTGF-a gene and it may do this in conjunction with corticotrophin-releasing factor, which is released centrally. The combination of these two factors will then be the regulators of puberty and the lack of these during childhood life means that gonadotrophin production is quiescent. The relationship between leptin and body fat brings the work of Frisch back into pre-eminence in the relationship between body fat and menarche. Children who develop anorexia nervosa prior to menarche do not menstruate spontaneously at the expected age and not until their body fat has risen to approximately15% do they begin to enter puberty. Weight loss post-menarche also leads to amenorrhoea as a result of suppression of GnRH production and the relationship between body fat and amenorrhoea may well be mediated through leptin production. In evolutionary terms, this phenomenon is extremely important because, at the time when we were hunter/gatherers, times of famine would be undesirable times for women to be pregnant; thus decreasing body fat leads to amenorrhoea and infertility and only when the female body has su⁄cient stores to guarantee adequate sustenance of the fetus, does the menstrual cycle return with subsequent restoration of fertility. Similarly, childhood is undesirable for pregnancy and thus suppression of the hypothalamo-pituitary-ovarian axis is physiologically necessary. Further work needs to be done to elucidate this phenomenon and while this hypothesis is tempting, it may not be the complete explanation for the control of the onset of puberty.
PRACTICE POINTS K
K
K
Aims: The identi¢cation of variations or abnormalities in the onset of puberty and the di¡erentiation between normal variants and disease Management: A detailed knowledge of the physiology allows explanation to parents and patients of normal variants. Identi¢cation of other medical factors a¡ecting the onset of puberty allows treatment of these, e.g. anorexia nervosa Investigations: These include menstrual charts, pelvic ultrasound to identify any anomalies and measurement of FSH, LH and oestradiol to identify any hypothalamic or ovarian abnormality
151
MENSTRUATION Menarche occurs at around 12.5 years in the UK. This age of menarche has remained fairly static over the last 20 ^25 years, although it has fallen considerably since the beginning of this century. Around the world, data exist to show that there is a direct relationship between the onset of menarche and socio-economic factors, which in turn re£ects the nutritional status of the population, thereby allowing the onset of puberty to occur earlier in the well-nourished adolescent as opposed to the nutritionally deprived. The ¢rst year after menarche may bring cycles that are irregular; this anovulatory phenomenon occurs in around 85% of girls. In fact, it takes on average 8 years for all normal females to establish a fully functional ovulatory cycle on a monthly basis. This phenomenon of anovulatory cycles is normal but may well lead to dysfunctional uterine bleeding; a similar phenomenon exists in the 10 years premenopausally for many women. These extremes of menstrual life exhibit very similar endocrine functional aberrations which almost certainly result from erratic GnRH production. In adolescent girls presenting with menstrual disturbance, the symptoms that are usually seen are either menorrhagia, metrorrhagia and/or dysmenorrhoea. The phenomenon of prolonged irregular, heavy bleeding is well known to gynaecologists in association with anovulatory cycles and poor cycle control. In screening these teenagers for their problem, simple techniques should be used in order to establish just how abnormal the situation is. It is di⁄cult to establish a quantitative history of bleeding from adolescent girls and even more di⁄cult when their mother is present.These are disturbing times and understandably maternal anxiety often leads to some exaggeration of the symptom complex. However, screening using simple measurements of haemoglobin and/or ferritin will establish whether or not the bleeding is signi¢cant. If these results are normal then the approach to the problem is one of reassurance, the identi¢cation of menstrual pattern using a menstrual calendar and regular review every 6 months, until the menstrual cycle becomes established and controlled. As the physiological sequence of events is the establishment of this normal cycle, one can be quite reassured if everything is normal. In girls who have some signi¢cant fall in haemoglobin, with levels between 10 and 12 g/dl, some therapeutic approach is necessary.The aetiology of the problem is almost always the same, but the failure to produce adequate amounts of oestradiol following the onset of menstruation means that endometrial cell growth is very poor and therefore the arteriolar openings on the inner surface of the endometrium remain uncovered and bleeding persists. In these circumstances, although progestogens in high doses may be helpful, they often fail to control the cycle adequately because some oestrogen is
152
required for this cell growth. Here, the oral contraceptive pill may be very useful and an explanation as to why it is required, to both mother and patient, is essential for co-operation in the taking of this. Many parents are understandably concerned about the use of the contraceptive pill in girls under the age of16, as they believe that it may encourage promiscuity. There is absolutely no psycho-social data to support this belief and mothers in particular need to be reassured that this is a therapeutic approach for their daughter to control her menstruation. Again, the menstrual cycle will eventually become established and the use of the oral contraceptive pill does not interfere with the maturation process of the hypothalamus. It is therefore pertinent to advise that if contraception is not necessary, these girls can consider withdrawal from the oral contraceptive pill at annual intervals until such time as their withdrawal is followed by regular menses, which cause them no trouble as they are a re£ection of normality. Finally, in the severely anaemic girl, before such a therapeutic approach as outlined above is entered into, it is very important to carry out a clinical assessment to exclude other diseases.This should involve an ultrasound of the pelvis and may include clotting studies for the identi¢cation of haematological abnormalities or coagulation disorders, which may very rarely present in this way. The previous estimates of the incidence of haematological disorders in these girls have recently been reduced, from 20% to 5%, but admission in acute episodes should include a coagulation screen. It should be noted that 30% of adolescents who present with abnormal menstrual function will subsequently present with menstrual dysfunction in later life, which probably re£ects a similar hypothalamic dysfunction as occurs during their adolescent years. Of speci¢c concern is the treatment of menstrual dysfunction in mentally handicapped adolescents. Here, carers and parents may well be distressed by menstruation, which may not be identi¢ed by the patient and therefore, from a sanitary point of view, creates some considerable di⁄culties. There is also concern over contraception and in considering both the control of menstruation and contraception it is highly desirable to create an environment of amenorrhoea. Many of these handicapped girls are on multiple medications, often for the control of epilepsy, and therefore the use of the oral contraceptive pill may or may not be suitable. Breakthrough bleeding on the pill, in spite of using elevated doses of oestrogen, may be worse than the phenomenon that they came with. It is, therefore, worth considering either Depo provera or Etonogestrel subdermal implant (Implanon.Organon), which may be the most appropriate ways of creating amenorrhoea. The advantage of the subdermal implant is that if side-e¡ects do occur then it can be removed. It has also recently been suggested that the Levonorgestrel intrauterine system can also be used
CURRENT OBSTETRICS & GYNAECOLOGY
to create both amenorrhoea and contraception for these patients. PRACTICE POINTS K
K
K
Aims: The reassurance of mother and child as to normal menstrual variation and the treatment of those variations that result in anaemia Management: Explanation of the normal pattern of menstrual loss and its excellent prognosis.The use of haematinics and oral contraceptive therapy in the management and prevention of menorrhagia. The use of non-steroidal anti-in£ammatories for the treatment of dysmenorrhoea Investigations: Measurement of haemoglobin and pelvic ultrasound allows a strategy for management to be identi¢ed
CONTRACEPTION Teenage contraception and unwanted teenage pregnancy has become a serious political issue in recent times. In the UKwe have done particularly badly with our strategies to reduce teenage pregnancy and in the last 30 years, almost no impact has occurred during that time in reducing the rates of unwanted pregnancy. While the debate about techniques for the development of adolescent and teenage pregnancy prevention should be discussed elsewhere, in the light of adolescent gynaecological practice, I think it is important that we be aware of the current concerns. Recent studies by the Social Exclusion Unit of the current UK government led to the startling information that a comparison of Dutch and British practice shows stark di¡erences in a number of areas. Teenagers who have been pregnant previously are more likely to conceive again and this is an area where counselling over contraceptive advice needs to be dramatically improved. However, in trying to improve the situation with regard to ¢rst time unwanted pregnancy, most pregnancies occur because of the use of no contraception whatsoever. Interestingly, the Dutch studies show that the vast majority of teenage girls (60 ^ 80%) receive their sex education from their mothers.This education at home is also a phenomenon for boys and 60% of boys receive their sex education from their fathers. Sadly, less than10% of British fathers are the source of contraceptive education for their sons and therefore the use of the condom by teenage boys during sexual encounters is very low indeed and, as it is well known that boys use their fathers as role models, if their fathers fail to educate them in good contraceptive practice then it is not surprising that the male half of these encounters is far from responsible in contraceptive practice. There needs to be a major change in the British attitude to contraception and
ADOLESCENT GYNAECOLOGY
paternal education if we are to improve the situation in the longer term and this seems, more than anything else, to be a factor where social change could have a serious impact on unwanted teenage pregnancy. Finally, we must accept that all human beings will eventually have the urge for sexual intercourse and failures will occur, in spite of all our e¡orts over contraception and education. The morning after pill must be readily available to all teenagers if they require it, in order to minimize the chances of them conceiving.Recent legislation has made this available in the UK over the counter, a controversial decision, but one which has a considerable degree of sociopolitical responsibility.
PRACTICE POINTS K
K
Aims: The reduction of the unwanted teenage pregnancy rate Management: The recognition that sex education in its current form has not reduced the unwanted teenage pregnancy rate. The education of fathers in their role of the teaching of contraceptive practice to their sons. The introduction of the morning after pill across the counter
OBSTRUCTIVE DISORDERS OF THE GENITALTRACT Primary amenorrhoea may occur in the presence of normal secondary sexual characteristic development and here obstructive disorders may play a role. Obstruction may occur either through a transverse vaginal septum or a longitudinal vaginal septum, although the longitudinal septum is not associated with amenorrhoea. Here the functional hemi-uteri drain on one side normally, giving a menstrual £ow, but the other side drains into a blind hemi-vagina, which increases in size and causes increasing pain. Cyclical abdominal pain in the teenager, therefore, that does not respond to normal analgesia, demands imaging. Ultrasound is more than adequate in demonstrating the presence of a haematocolpos. This may result from an intact hymen and here the surgical resolution of this problem is straightforward. However, if the obstructive disorder is due to a longitudinal septum or a transverse septum, then the surgery should be carried out to remove these septae by surgeons who have a considerable expertise in these disorders. If this surgery is not carried out correctly, then subsequent stenoses or infection may occur, either leading to dyspareunia, which is di⁄cult to resolve at subsequent surgical procedures, or in cases of sepsis, fertility may be lost. It cannot be emphasized enough as to how important it is to perform the correct operation the ¢rst time, if the
153
girl is to be resolved of her di⁄culty and have the greatest potential for her sex-life and reproductive function in the long term.
CONGENITAL ABSENCE OF THE VAGINA Congenital absence of the vagina (the Rokitansky syndrome) is the second most common cause of primary amenorrhoea in the UK. It is second only to Turner’s syndrome. Normal secondary sexual characteristics are present and an examination reveals a dimple where the vagina ought to be. The incidence of this disorder is around 1: 4000 female births and it is a polygenic problem with genes almost certainly located on chromosome 16. The genes are probably contained in a homeobox, a group of genes that are responsible for the development of a particular organ group, and any mutation or deletion of the genes will lead to variable developmental disorders in this syndrome. Attempts to identify the genes responsible have so far been unsuccessful. The uterus itself will not be developed and the vagina will be absent. While at the present time there are no possibilities of creating a uterus, a functional vagina can be achieved in almost all women.The non-surgical approach is associated with a sexual success rate of around 85% and therefore only15% of girls with this problem need be subjected to surgery. Whenever this type of condition arises, the most important approach is a holistic one.The anatomical defect is not the most important part of these girls’ problems and the psychological disturbance that occurs in association with pubertyFlearning that you do not have the ability to have a period, that you cannot be sexually functional without help, and ¢nally that you are involuntarily infertileFis a major psychological blow. These girls become very depressed and anxious, have doubts about their gender and in some cultures, where female reproduction is of such overwhelming importance to the female role in society, the psychological blow can be extremely traumatic. Thus, in dealing with problems along these lines, it is imperative that centres have psychological support, clinical nurse specialists and a self-help group, as co-counselling is a cornerstone of managing these girls. Not until their psychological problems are resolved is it possible to approach the anatomical di⁄culties that they have, in the hope of getting a functionally good result. Fortunately, this is more than possible with the correct set-up, but these girls are poorly served by managing independently and without the expertise they need. In approaching the creation of a vagina, the use of graduated dilators to stretch the short vagina is successful in 85% of girls and should be the treatment of ¢rst choice. These ¢gures of success will only result if the
154
CURRENT OBSTETRICS & GYNAECOLOGY
whole team is involved in the management of the patient. In those girls who fail to achieve a vagina this way, a surgical approach may be needed. Here, a number of materials have been used over the years to try to line the neovaginal space and these include partial thickness skin grafts, amnion, peritoneum and some of the newer matrix barriers. All of the techniques at the present time have a success rate of around 80% and the failure is usually the result of contracture of the neo-vagina due to failure of the use of either a mould or dilators in the postoperative period. Considerable reliance on the patient herself is required for such a successful result and here the emphasis on psychological maturity is important. The prospect of tissue-engineered grafts holds new hope for the future such that contracture will be less common a problem. While they do not have a functional uterus, surrogacy for these women is more than possible and recent reports from North America show that success with surrogacy is high. Of all the female children born to these women so far, an ultrasound assessment of the pelvis has revealed the presence of a uterus and therefore the inheritance of these disorders is not a dominant one. In polygenic abnormalities it would be expected that a recurrence rate of 2^5% would be seen and as there are so far less than 50 female infants born, it is still more than possible that this phenomenon of the Rokitansky syndrome will occur in the o¡spring of one of these women.
K
K
further elucidate the control of the onset of puberty Methods of trying to change attitudes on contraception The identi¢cation of the genes involved in genital development
CONCLUSION The transition through puberty to adulthood is a di⁄cult and complex time in female development, which involves both physical, endocrine and intellectual maturation.The importance of understanding the physiological processes and the impact these have on clinical conditions is paramount to any clinician who is managing adolescent gynaecology and some of the aspects of this di⁄cult time are discussed in this article. There are still wide areas of understanding that need to be elucidated and these include greater knowledge of control of the onset of puberty and the genetic control of internal and external genitalia. When this knowledge is forthcoming, therapeutic techniques will change in order to try to ensure that these patients have minimal impact from these conditions on their lives.
FURTHER READING PRACTICE POINTS K
K
K
Aims: To identify the presence of congenital abnormalities and manage them appropriately Management: Obstructive disorders need to be managed in specialist centres by surgeons with the skills to achieve appropriate surgical results. The management of congenital absence of the vagina requires a holistic approach, including a wide range of health professionals Investigations: Clinical examination and ultrasound. Occasionally MRI
RESEARCH DIRECTIONS K
The interaction between the arcuate nucleus of the hypothalamus and central control that will
Dewhurst CJ. Female Puberty and its Abnormalities. Edinburgh: Churchill Livingstone,1982; 30 ^32. Edmonds DK. Sexual developmental anomalies and their reconstruction. In: San¢lippo J (ed). Pediatric and Adolescent Gynecology. Philadelphia: W. B. Saunders,1994; 544 ^565. Edmonds DK. Leptin and the onset of puberty. Curr Opin Obstet Gynecol 1998; 10: 361^363. Edmonds DK. Dysfunctional uterine bleeding in adolescence. In: Smith S (ed). Baillieres Clinical Obstetrics and Gynaecology,Vol.13. London: Bailliere & Tindall,1999; 239^249. Edmonds DK.Congenital malformations of genital tract. In: Berenson A (ed). Obstetrics and Gynecology Clinics of North America. Philadelphia: W. B. Saunders, 2000; 49^ 62. Lee PA. The neuroendocrinology of puberty. Semin Reprod Med 1988; 6: 13^20. Moore KL, Persaud TVN. The Developing Human. Philadelphia: W. B. Saunders,1993. Yen SCC. The hypothalamic control of pituitary hormone function. In: Yen SCC, Ja¡e RB (eds). Reproductive Endocrinology, 3rd edition. Philadelphia: W. B. Saunders1991: 132^158.
c 2002 Elsevier Science Ltd doi:10.1054/cuog.2001.0251 available online at http://www.idealibrary.com on
Adolescent gynaecology D. Keith Edmonds Consultant Obstetrician and Gynaecologist, Queen Charlotte’s Hospital, Du Cane Road, London W12 0HS, UK
KEYWORDS adolescent gynaecology; puberty; primary amenorrhoea; menstrual disturbance; vaginal anomalies; contraception
Summary The transition of a female from childhood to adulthood is a complex process.The control ofthe onsetof pubertyis normally anuneventful sequence of events but disorders may lead to dysfunction in the menstrual cycle or be a symptom of other diseases, such as anorexia nervosa.Failure to establish pubertyneeds treatmentin specialistcentres as does the managementof primary amenorrhoea and the surgical aspects of this problem are referred to in the text.These disorders may be obstructive or due to congenital absence ofthe vagina.This article discusses some ofthe aspects of adolescent gynaecology, whichillustrates the need for a specialistknowledge to manage these cases correctly. & 2002 Elsevier Science Ltd
INTRODUCTION Adolescent gynaecology concerns aspects of developmental and functional defects in addressing the transition from childhood to the fully fertile female. The adolescent is a complex individual undergoing dramatic physiological and anatomical changes and these changes involve complex endocrine interactions with a subsequent anatomical response which will allow reproduction of the species when these processes are complete. Disorders of this process are fortunately uncommon but when they are present, they have a dramatic impact on the individual both physically, emotionally and intellectually and these are most dramatic when there is a failure to be able to ful¢l this reproductive function.
CONTROLOF THE ONSETOF PUBERTY The fetal gonad is identi¢able as an ovary at around 7^ 8 weeks’ gestation and evidence of hypothalamo-pituitary function is demonstrable at around 10 ^12 weeks’ gestation. By16 weeks’ gestation, FSH and LH levels have risen to signi¢cant proportions and by 20 weeks’ gestation the hypothalamo-pituitary ovarian axis is functional. The number of oocytes within the ovary at this gestation is approximately 5.9 million, but subsequent massive atresia, possibly due to a form of apoptosis, means that at birth this oocyte count is reduced to around 2 million. The latter part of pregnancy is associated with placental production of oestriol and rising levels of oestriol pass Correspondence to: DKE.Tel: +44 (0)20 8383 3586; Fax: + 44 (0)20 8383 3419; E-mail: [email protected]
into the fetal circulation causing negative feedback on the hypothalamus, thereby reducing circulating levels of FSH within the fetus.This phenomenon further supports the concept of an intact hypothalamo-pituitary-ovarian axis prior to birth. Following birth the female neonate has its source of oestriol withdrawn when the umbilical cord is severed and inhibition of the hypothalamus ceases leading to elevated levels of FSH, sometimes as high as castrate levels, which remain elevated in the ¢rst 9 months to 1 year following birth. This phenomenon may lead to activation of oocytes within the ovary, although the frequency and amplitude of the pulses of GnRH are chaotic. Oestradiol may well be produced during this ¢rst year of life at su⁄cient levels to induce endometrial growth and occasionally menstrual loss or growth of the breast bud. This important piece of physiology must be remembered when female infants present with these symptoms. By the end of the ¢rst year of life, or at the latest 18 months, gonadotrophins are suppressed and levels of FSH are almost unrecordable throughout childhood. Around age 8 or 9, single pulses of GnRH begin nocturnally at around 04:00 h.Over the ensuing 4 years, increase in nocturnal frequency and amplitude progresses into day-time pulses, which eventually, at around age 12.5 years, results in the establishment of the fully functional hypothalamo-pituitary-ovarian axis, which leads on to menarche and thereafter to co-ordinated ovulatory cycles and reproductive potential. The control mechanism for the down-regulation of FSH after the ¢rst year of life and the re-establishment in late childhood, remains speculative. However, it is more than possible that this may be controlled through the production of leptin, a product of fat cell metabolism. The neurones of the GnRH-producing cell lie in the arcuate nucleus of the hypothalamus. Receptors on the
ADOLESCENT GYNAECOLOGY
cell surface for aspartate and epidermal growth factor are now known to control whether the cell is activated and therefore produces GnRH, or whether it is inactivated, as in the hypogonadotrophic state. It is postulated that the gene for transforming growth factor alpha (TGF-a) may regulate this receptor expression, thereby controlling the production of gonadotrophins.There are animal data to support the concept that leptin may control theTGF-a gene and it may do this in conjunction with corticotrophin-releasing factor, which is released centrally. The combination of these two factors will then be the regulators of puberty and the lack of these during childhood life means that gonadotrophin production is quiescent. The relationship between leptin and body fat brings the work of Frisch back into pre-eminence in the relationship between body fat and menarche. Children who develop anorexia nervosa prior to menarche do not menstruate spontaneously at the expected age and not until their body fat has risen to approximately15% do they begin to enter puberty. Weight loss post-menarche also leads to amenorrhoea as a result of suppression of GnRH production and the relationship between body fat and amenorrhoea may well be mediated through leptin production. In evolutionary terms, this phenomenon is extremely important because, at the time when we were hunter/gatherers, times of famine would be undesirable times for women to be pregnant; thus decreasing body fat leads to amenorrhoea and infertility and only when the female body has su⁄cient stores to guarantee adequate sustenance of the fetus, does the menstrual cycle return with subsequent restoration of fertility. Similarly, childhood is undesirable for pregnancy and thus suppression of the hypothalamo-pituitary-ovarian axis is physiologically necessary. Further work needs to be done to elucidate this phenomenon and while this hypothesis is tempting, it may not be the complete explanation for the control of the onset of puberty.
PRACTICE POINTS K
K
K
Aims: The identi¢cation of variations or abnormalities in the onset of puberty and the di¡erentiation between normal variants and disease Management: A detailed knowledge of the physiology allows explanation to parents and patients of normal variants. Identi¢cation of other medical factors a¡ecting the onset of puberty allows treatment of these, e.g. anorexia nervosa Investigations: These include menstrual charts, pelvic ultrasound to identify any anomalies and measurement of FSH, LH and oestradiol to identify any hypothalamic or ovarian abnormality
151
MENSTRUATION Menarche occurs at around 12.5 years in the UK. This age of menarche has remained fairly static over the last 20 ^25 years, although it has fallen considerably since the beginning of this century. Around the world, data exist to show that there is a direct relationship between the onset of menarche and socio-economic factors, which in turn re£ects the nutritional status of the population, thereby allowing the onset of puberty to occur earlier in the well-nourished adolescent as opposed to the nutritionally deprived. The ¢rst year after menarche may bring cycles that are irregular; this anovulatory phenomenon occurs in around 85% of girls. In fact, it takes on average 8 years for all normal females to establish a fully functional ovulatory cycle on a monthly basis. This phenomenon of anovulatory cycles is normal but may well lead to dysfunctional uterine bleeding; a similar phenomenon exists in the 10 years premenopausally for many women. These extremes of menstrual life exhibit very similar endocrine functional aberrations which almost certainly result from erratic GnRH production. In adolescent girls presenting with menstrual disturbance, the symptoms that are usually seen are either menorrhagia, metrorrhagia and/or dysmenorrhoea. The phenomenon of prolonged irregular, heavy bleeding is well known to gynaecologists in association with anovulatory cycles and poor cycle control. In screening these teenagers for their problem, simple techniques should be used in order to establish just how abnormal the situation is. It is di⁄cult to establish a quantitative history of bleeding from adolescent girls and even more di⁄cult when their mother is present.These are disturbing times and understandably maternal anxiety often leads to some exaggeration of the symptom complex. However, screening using simple measurements of haemoglobin and/or ferritin will establish whether or not the bleeding is signi¢cant. If these results are normal then the approach to the problem is one of reassurance, the identi¢cation of menstrual pattern using a menstrual calendar and regular review every 6 months, until the menstrual cycle becomes established and controlled. As the physiological sequence of events is the establishment of this normal cycle, one can be quite reassured if everything is normal. In girls who have some signi¢cant fall in haemoglobin, with levels between 10 and 12 g/dl, some therapeutic approach is necessary.The aetiology of the problem is almost always the same, but the failure to produce adequate amounts of oestradiol following the onset of menstruation means that endometrial cell growth is very poor and therefore the arteriolar openings on the inner surface of the endometrium remain uncovered and bleeding persists. In these circumstances, although progestogens in high doses may be helpful, they often fail to control the cycle adequately because some oestrogen is
152
required for this cell growth. Here, the oral contraceptive pill may be very useful and an explanation as to why it is required, to both mother and patient, is essential for co-operation in the taking of this. Many parents are understandably concerned about the use of the contraceptive pill in girls under the age of16, as they believe that it may encourage promiscuity. There is absolutely no psycho-social data to support this belief and mothers in particular need to be reassured that this is a therapeutic approach for their daughter to control her menstruation. Again, the menstrual cycle will eventually become established and the use of the oral contraceptive pill does not interfere with the maturation process of the hypothalamus. It is therefore pertinent to advise that if contraception is not necessary, these girls can consider withdrawal from the oral contraceptive pill at annual intervals until such time as their withdrawal is followed by regular menses, which cause them no trouble as they are a re£ection of normality. Finally, in the severely anaemic girl, before such a therapeutic approach as outlined above is entered into, it is very important to carry out a clinical assessment to exclude other diseases.This should involve an ultrasound of the pelvis and may include clotting studies for the identi¢cation of haematological abnormalities or coagulation disorders, which may very rarely present in this way. The previous estimates of the incidence of haematological disorders in these girls have recently been reduced, from 20% to 5%, but admission in acute episodes should include a coagulation screen. It should be noted that 30% of adolescents who present with abnormal menstrual function will subsequently present with menstrual dysfunction in later life, which probably re£ects a similar hypothalamic dysfunction as occurs during their adolescent years. Of speci¢c concern is the treatment of menstrual dysfunction in mentally handicapped adolescents. Here, carers and parents may well be distressed by menstruation, which may not be identi¢ed by the patient and therefore, from a sanitary point of view, creates some considerable di⁄culties. There is also concern over contraception and in considering both the control of menstruation and contraception it is highly desirable to create an environment of amenorrhoea. Many of these handicapped girls are on multiple medications, often for the control of epilepsy, and therefore the use of the oral contraceptive pill may or may not be suitable. Breakthrough bleeding on the pill, in spite of using elevated doses of oestrogen, may be worse than the phenomenon that they came with. It is, therefore, worth considering either Depo provera or Etonogestrel subdermal implant (Implanon.Organon), which may be the most appropriate ways of creating amenorrhoea. The advantage of the subdermal implant is that if side-e¡ects do occur then it can be removed. It has also recently been suggested that the Levonorgestrel intrauterine system can also be used
CURRENT OBSTETRICS & GYNAECOLOGY
to create both amenorrhoea and contraception for these patients. PRACTICE POINTS K
K
K
Aims: The reassurance of mother and child as to normal menstrual variation and the treatment of those variations that result in anaemia Management: Explanation of the normal pattern of menstrual loss and its excellent prognosis.The use of haematinics and oral contraceptive therapy in the management and prevention of menorrhagia. The use of non-steroidal anti-in£ammatories for the treatment of dysmenorrhoea Investigations: Measurement of haemoglobin and pelvic ultrasound allows a strategy for management to be identi¢ed
CONTRACEPTION Teenage contraception and unwanted teenage pregnancy has become a serious political issue in recent times. In the UKwe have done particularly badly with our strategies to reduce teenage pregnancy and in the last 30 years, almost no impact has occurred during that time in reducing the rates of unwanted pregnancy. While the debate about techniques for the development of adolescent and teenage pregnancy prevention should be discussed elsewhere, in the light of adolescent gynaecological practice, I think it is important that we be aware of the current concerns. Recent studies by the Social Exclusion Unit of the current UK government led to the startling information that a comparison of Dutch and British practice shows stark di¡erences in a number of areas. Teenagers who have been pregnant previously are more likely to conceive again and this is an area where counselling over contraceptive advice needs to be dramatically improved. However, in trying to improve the situation with regard to ¢rst time unwanted pregnancy, most pregnancies occur because of the use of no contraception whatsoever. Interestingly, the Dutch studies show that the vast majority of teenage girls (60 ^ 80%) receive their sex education from their mothers.This education at home is also a phenomenon for boys and 60% of boys receive their sex education from their fathers. Sadly, less than10% of British fathers are the source of contraceptive education for their sons and therefore the use of the condom by teenage boys during sexual encounters is very low indeed and, as it is well known that boys use their fathers as role models, if their fathers fail to educate them in good contraceptive practice then it is not surprising that the male half of these encounters is far from responsible in contraceptive practice. There needs to be a major change in the British attitude to contraception and
ADOLESCENT GYNAECOLOGY
paternal education if we are to improve the situation in the longer term and this seems, more than anything else, to be a factor where social change could have a serious impact on unwanted teenage pregnancy. Finally, we must accept that all human beings will eventually have the urge for sexual intercourse and failures will occur, in spite of all our e¡orts over contraception and education. The morning after pill must be readily available to all teenagers if they require it, in order to minimize the chances of them conceiving.Recent legislation has made this available in the UK over the counter, a controversial decision, but one which has a considerable degree of sociopolitical responsibility.
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Aims: The reduction of the unwanted teenage pregnancy rate Management: The recognition that sex education in its current form has not reduced the unwanted teenage pregnancy rate. The education of fathers in their role of the teaching of contraceptive practice to their sons. The introduction of the morning after pill across the counter
OBSTRUCTIVE DISORDERS OF THE GENITALTRACT Primary amenorrhoea may occur in the presence of normal secondary sexual characteristic development and here obstructive disorders may play a role. Obstruction may occur either through a transverse vaginal septum or a longitudinal vaginal septum, although the longitudinal septum is not associated with amenorrhoea. Here the functional hemi-uteri drain on one side normally, giving a menstrual £ow, but the other side drains into a blind hemi-vagina, which increases in size and causes increasing pain. Cyclical abdominal pain in the teenager, therefore, that does not respond to normal analgesia, demands imaging. Ultrasound is more than adequate in demonstrating the presence of a haematocolpos. This may result from an intact hymen and here the surgical resolution of this problem is straightforward. However, if the obstructive disorder is due to a longitudinal septum or a transverse septum, then the surgery should be carried out to remove these septae by surgeons who have a considerable expertise in these disorders. If this surgery is not carried out correctly, then subsequent stenoses or infection may occur, either leading to dyspareunia, which is di⁄cult to resolve at subsequent surgical procedures, or in cases of sepsis, fertility may be lost. It cannot be emphasized enough as to how important it is to perform the correct operation the ¢rst time, if the
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girl is to be resolved of her di⁄culty and have the greatest potential for her sex-life and reproductive function in the long term.
CONGENITAL ABSENCE OF THE VAGINA Congenital absence of the vagina (the Rokitansky syndrome) is the second most common cause of primary amenorrhoea in the UK. It is second only to Turner’s syndrome. Normal secondary sexual characteristics are present and an examination reveals a dimple where the vagina ought to be. The incidence of this disorder is around 1: 4000 female births and it is a polygenic problem with genes almost certainly located on chromosome 16. The genes are probably contained in a homeobox, a group of genes that are responsible for the development of a particular organ group, and any mutation or deletion of the genes will lead to variable developmental disorders in this syndrome. Attempts to identify the genes responsible have so far been unsuccessful. The uterus itself will not be developed and the vagina will be absent. While at the present time there are no possibilities of creating a uterus, a functional vagina can be achieved in almost all women.The non-surgical approach is associated with a sexual success rate of around 85% and therefore only15% of girls with this problem need be subjected to surgery. Whenever this type of condition arises, the most important approach is a holistic one.The anatomical defect is not the most important part of these girls’ problems and the psychological disturbance that occurs in association with pubertyFlearning that you do not have the ability to have a period, that you cannot be sexually functional without help, and ¢nally that you are involuntarily infertileFis a major psychological blow. These girls become very depressed and anxious, have doubts about their gender and in some cultures, where female reproduction is of such overwhelming importance to the female role in society, the psychological blow can be extremely traumatic. Thus, in dealing with problems along these lines, it is imperative that centres have psychological support, clinical nurse specialists and a self-help group, as co-counselling is a cornerstone of managing these girls. Not until their psychological problems are resolved is it possible to approach the anatomical di⁄culties that they have, in the hope of getting a functionally good result. Fortunately, this is more than possible with the correct set-up, but these girls are poorly served by managing independently and without the expertise they need. In approaching the creation of a vagina, the use of graduated dilators to stretch the short vagina is successful in 85% of girls and should be the treatment of ¢rst choice. These ¢gures of success will only result if the
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CURRENT OBSTETRICS & GYNAECOLOGY
whole team is involved in the management of the patient. In those girls who fail to achieve a vagina this way, a surgical approach may be needed. Here, a number of materials have been used over the years to try to line the neovaginal space and these include partial thickness skin grafts, amnion, peritoneum and some of the newer matrix barriers. All of the techniques at the present time have a success rate of around 80% and the failure is usually the result of contracture of the neo-vagina due to failure of the use of either a mould or dilators in the postoperative period. Considerable reliance on the patient herself is required for such a successful result and here the emphasis on psychological maturity is important. The prospect of tissue-engineered grafts holds new hope for the future such that contracture will be less common a problem. While they do not have a functional uterus, surrogacy for these women is more than possible and recent reports from North America show that success with surrogacy is high. Of all the female children born to these women so far, an ultrasound assessment of the pelvis has revealed the presence of a uterus and therefore the inheritance of these disorders is not a dominant one. In polygenic abnormalities it would be expected that a recurrence rate of 2^5% would be seen and as there are so far less than 50 female infants born, it is still more than possible that this phenomenon of the Rokitansky syndrome will occur in the o¡spring of one of these women.
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further elucidate the control of the onset of puberty Methods of trying to change attitudes on contraception The identi¢cation of the genes involved in genital development
CONCLUSION The transition through puberty to adulthood is a di⁄cult and complex time in female development, which involves both physical, endocrine and intellectual maturation.The importance of understanding the physiological processes and the impact these have on clinical conditions is paramount to any clinician who is managing adolescent gynaecology and some of the aspects of this di⁄cult time are discussed in this article. There are still wide areas of understanding that need to be elucidated and these include greater knowledge of control of the onset of puberty and the genetic control of internal and external genitalia. When this knowledge is forthcoming, therapeutic techniques will change in order to try to ensure that these patients have minimal impact from these conditions on their lives.
FURTHER READING PRACTICE POINTS K
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Aims: To identify the presence of congenital abnormalities and manage them appropriately Management: Obstructive disorders need to be managed in specialist centres by surgeons with the skills to achieve appropriate surgical results. The management of congenital absence of the vagina requires a holistic approach, including a wide range of health professionals Investigations: Clinical examination and ultrasound. Occasionally MRI
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The interaction between the arcuate nucleus of the hypothalamus and central control that will
Dewhurst CJ. Female Puberty and its Abnormalities. Edinburgh: Churchill Livingstone,1982; 30 ^32. Edmonds DK. Sexual developmental anomalies and their reconstruction. In: San¢lippo J (ed). Pediatric and Adolescent Gynecology. Philadelphia: W. B. Saunders,1994; 544 ^565. Edmonds DK. Leptin and the onset of puberty. Curr Opin Obstet Gynecol 1998; 10: 361^363. Edmonds DK. Dysfunctional uterine bleeding in adolescence. In: Smith S (ed). Baillieres Clinical Obstetrics and Gynaecology,Vol.13. London: Bailliere & Tindall,1999; 239^249. Edmonds DK.Congenital malformations of genital tract. In: Berenson A (ed). Obstetrics and Gynecology Clinics of North America. Philadelphia: W. B. Saunders, 2000; 49^ 62. Lee PA. The neuroendocrinology of puberty. Semin Reprod Med 1988; 6: 13^20. Moore KL, Persaud TVN. The Developing Human. Philadelphia: W. B. Saunders,1993. Yen SCC. The hypothalamic control of pituitary hormone function. In: Yen SCC, Ja¡e RB (eds). Reproductive Endocrinology, 3rd edition. Philadelphia: W. B. Saunders1991: 132^158.