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«Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access distributed under the Creative ...»

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Edited by Amar Chatterjee


Edited by Amar Chatterjee

Published by InTech

Janeza Trdine 9, 51000 Rijeka, Croatia

Copyright © 2011 InTech

All chapters are Open Access distributed under the Creative Commons Attribution 3.0

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Publishing Process Manager Iva Simcic Technical Editor Teodora Smiljanic Cover Designer InTech Design Team Image Copyright Sebastian Kaulitzki, 2011. Used under license from Shutterstock.com First published November, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Amenorrhea, Edited by Amar Chatterjee p. cm.

ISBN 978-953-307-988-2 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Chapter 1 Hormonal Diagnosis of Menstrual Irregularities or Secondary Amenorrhoea 1 Ursula Zollner

Chapter 2 Chemotherapy-Related Amenorrhea in Breast Cancer:

Review of the Main Published Studies, Biomarkers of Ovarian Function and Mechanisms Involved in Ovarian Toxicity 13 M. Berliere, F.P. Duhoux, Ch. Galant, F. Dalenc, J.F. Baurain, I. Leconte, L. Fellah, L. Dellvigne, P. Piette and J.P. Machiels Chapter 3 Bone Mass in Anorexia Nervosa and Thin Postmenopausal Women-Related Secondary Amenorrhea 27 Mário Rui Mascarenhas, Ana Paula Barbosa, Zulmira Jorge, Ema Nobre, Ana Gonçalves, António Gouveia de Oliveira and Isabel do Carmo Chapter 4 Polycystic Ovar

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This book is a wonderful collection of updated reviews by a group of experts dealing mostly with the aphysiological aspects of secondary amenorrhea.

The eight chapters of the book describe the hormonal evaluation of secondary amenorrhea, chemotherapy-related amenorrhea in breast cancer, a direct link between the nutritional status in anorectic women with amenorrhea and whether it is comparable with the thin postmenopausal women with risk of osteoporosis and fragility fracture. Other aspects include different lines of treatment of polycystic ovarian syndrome (PCOS)-related infertility and other problems. PCOS-associated insulin resistance, hyperinsulinemia with hyperandrogenism and their possible therapeutic interruption, the management of congenital adrenal hyperplasia-related insulin resistance and amenorrhea. It also covers clinical results of two new levenorgestrel-releasing intrauterine systems to reduce menstrual blood loss compared to surgical intervention. A review of literature and new insights on amenorrhea and endometrial ablation has also been described. The final chapter discusses the recent clinical application of campo (herbal) medicines for the treatment of amenorrhea.

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1. Introduction In the daily clinical routine, clarification of menstrual irregularities is one of the major essentials for consultation in gynaecological practice. For an effective therapy, it is necessary to know the exact cause of the bleeding disorders. Menstrual irregularities can be the expression of a disturbed ovarian function or another disorder, usually uterine pathology. The type of menstrual irregularity is not necessarily indicative of the underlying disorder so that the examination of the levels of hormones is indispensable.

Moreover, an organic cause of the bleeding disorder should be excluded. Whether the ovulatory cycle is associated with normal follicle maturation and corpus luteum function has to be clarified in the treatment of childlessness. The existence of anovulatory cycles or cycles with corpus luteum insufficiency can be normal in specific phases of life, e.g., puberty or peri-menopause. The issue of therapy should be addressed briefly. Firstly, the symptoms such as bleeding disorders and the disease patterns which are responsible for it should be highlighted. The clarification of menstrual irregularities is not only important in sterility therapy, they also influence the quality of life (1). Furthermore, hormonal disorders which are associated with chronic oestrogen or progesterone deficiency have an impact on the overall health (2). The following review represents the diagnostics of hormone-related menstrual irregularities in the fertile phase of life. The issue of bleeding disorders with the application of hormone preparations is not addressed.

2. Diagnostics of menstrual irregularities Menstrual irregularities or bleeding disorders also include menstrual cycle-related symptoms such as dysmenorrhoea (1). During the classification of menstrual irregularities and/or bleeding disorders the only symptom which is assumed is bleeding, however, it does not contain any information about the cause of the deviation from regular menstrual cycles. A regular menstrual cycle with a 28-day bleeding interval in 85–90% of the cases is usually associated with normal ovarian function and corresponding ovulatory cycles (3).

The normal bleeding duration is between 3–7 days and is associated with a blood loss of 30–40 ml (1). Deviations in the form of menstrual bleed which occur too infrequently or too frequently can be the expression of a pathological disorder. The causes can be uterine 2 Amenorrhea pathology, other illnesses or ovarian dysfunction. It can be assumed that 90% of all bleeding disorders are hormone-related or partly hormone-related (4). The menstrual irregularity can express itself through a change of the bleeding pattern (menstrual rhythm abnormalities), the intensity of bleeding, its duration (type of menstrual abnormalities) or in the form of additional bleedings. The bleeding disorders are to be interpreted with the age and/or the reproductive phase of the woman, respectively. An oligomenorrhoea in a 26-year-old obese patient is most likely to be due to a PCO syndrome. However, in a 46year-old patient it probably indicates a perimenopausal condition. The physiological and/or the therapeutic menstrual irregularities must be disassociated from the pathological menstrual irregularities, e.g., the oligomenorrhoea in the perimenopause or the amenorrhoea under gestagen monotherapy.

3. Medical history Whilst reviewing the medical history, all previous and current diseases (disorders of the liver or kidney function, autoimmune diseases) are inquired about. The current complaints, the medication (influence of prolactin production) and the questions concerning androgen-induced disorders are just as important questions as the questions concerning contraception, desire to have children or previous pregnancies. Lifestyle (sleep, physical activity) and eating habits must not be underestimated because endocrinological problems occur frequently in both overweight and underweight women as well as in the competitive athletes. Even extreme weight fluctuations can have an impact on the ovarian function. In this conjunction, the extremely important question concerns the coagulation dysfunctions because the execution of anticoagulation can influence the bleeding duration and intensity. Furthermore, questions should be asked about the presence of endocrinopathies such as diabetes mellitus (type I), Addison disease, Cushing disease, previous operation on the uterus and or the ovaries and/or operation or trauma of the pituitary area.

4. Menstruation history During the medical history, attention should be paid to the exact increase in bleeding intervals. The patients often view their menstrual cycle is normal even if the intervals between them do not correspond to the standard of 24 to 34 days. However, a menstruation calendar can address the intervals, duration and the intensity of the bleeding. The estimation of the bleeding intensity is strongly influenced, therefore, number of sanitary towels and/or tampons per day is advised to be recorded. If lower abdominal pain is indicated then it is important to observe the temporal relation with the periods. A dysmenorrhoea can be a sentinel for an endometriosis. Premenstrual complaints such as headaches or mood swings can be the sign of premenstrual syndrome, an indication of corpus luteum insufficiency.

5. Clinical examinations It is important to note that an acyclic vaginal bleeding does not always need to be an expression of a disturbed ovarian function. A large number of other factors, e.g., colpitis, Hormonal Diagnosis of Menstrual Irregularities or Secondary Amenorrhoea ectopy, disturbed pregnancy or malignancies can become noticeable through a bleeding from the vagina and can often be diagnosed through the use of a speculum and/or a vaginal sonograpy. Physical and a gynaecological examination cannot be avoided during the diagnostic investigation of menstrual irregularities. The Body-Mass-Index, fat distribution pattern as well as androgen-induced disorders are very important, particularly in conjunction with the suspicion of PCO syndrome. During the gynaecological examination, infections, new formations or malformations of the internal genitals can be detected or excluded. Myomas, polyps or carcinomas should not be excluded as a cause for the bleeding. The vaginal sonography represents a substantial diagnosis test. By doing so, the condition and size of the uterus, endometrial thickness and the amount of layers as well as the form and the size of the ovaries can be assessed reliably. Follicular presence or absence is a good diagnostic criterion in assessing the egg cell reserve of the ovaries.

6. Hormonal diagnosis Suspected diagnoses can usually be made through the type of the menstruation irregularity, symptoms and the results of the gynaecological examinations, which can then either be confirmed or excluded through a differentiated laboratory diagnosis. Therefore, an obese patient with secondary oligomenorrhoea and polycystic ovaries most likely suffers from PCO syndrome or a hyperandrogenemia. Conversely, a slim competitive athlete with a secondary amenorrhoea probably suffers from hypogonadotropic ovarian insufficiency. The menstrual phase must be taken into consideration when a blood sample is taken for investigation. It is proved to be useful to carry out the examination in the early follicle phase that is 3rd–5th days of menstruation. In secondary amenorrhoea, the question of selecting menstrual phase does not arise. The interpretation of hormones within the framework of the menstrual events implies the knowledge of the day of menstruation, the length of menstruation, the sequential secretion of the individual hormones during the course of a menstrual cycle and the relationship to one another (2, 8). The following hormones can be determined during the basic diagnostics (basic hormone analysis, [BHA], 3rd–5th days of the menstrual cycle). The following blood test should be done in a stress-free morning in early

follicle phase:

 FSH (follicle-stimulating hormone)  LH (luteinizing hormone)  E2 (estradiol)  Progesterone  Prolactin  Testosterone  Androstenedione  DHEAS (dehydroepiandrosterone sulphate)  17-OH-Progesterone  TSH (thyroid-stimulating hormone) Depending on the assumed disease pattern, not all hormones need to be examined, rather it can be limited to the most relevant ones (see below). Table 1 shows the normal values of these hormones.

4 Amenorrhea

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7. Monitoring the menstrual cycle If a largely inconspicuous menstrual rhythm is present, it is interesting in sterility diagnosis to see whether it really leads to ovulation or to a stable luteal phase. Follicle maturation disorder or corpus luteum insufficiency cannot be diagnosed through only one single blood test. Several examinations concerning the menstrual cycle are necessary. In this connection, the vaginal sonography can be implemented in addition to the laboratory diagnosis. One

would expect the following values in such a diagnostic cycle:

 Day 3-5: BHA values are normal (see Table 1) Vaginal sonography: small endometrium, ovaries with a few small preantral follicles  Day 12-14: LH normal or ↑, estradiol 150 pg/ml Vaginal sonography: endometrium approx. 10 mm, mostly three-layered, dominant follicle approx. 16-20 mm  Day 21: Progesterone 10 ng/ml Vaginal sonography: endometrium approx. 10 mm, homogeneous, Corpus luteum with interior echoes In the case of deviations, conclusion about the underlying disorder can be drawn. The carrying out of LH-urine tests for the determination of ovulation period which indicates the pre-ovulatory LH surge in the spontaneous menstrual cycle is in practice (5). Both the FSH levels and FSH/LH ratio (for values 3.6 a reduced build up of follicles must be expected) as well as the AMH (Anti-Müller hormone) are used for evaluation of the ovarian reserve.

8. Practical approaches to the individual menstrual irregularity In 1987, Hammerstein tried to classify the bleeding disorders according to their causes (9).

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