Primary amenorrhoea

Primary amenorrhoea is defined as the absence of menstruation by age 14 years in the absence of secondary sexual characteristics, or by age 16 years if secondary sexual characteristics are present. Regular menstruation is regarded as a sign of reproductive health thus absent menstruation causes a significant degree of stress and anxiety to the individuals involved. Puberty is governed by a complex neuro-hormonal system with input from multiple endogenous and exogenous factors, and pathology at various levels in this system can result in amenorrhoea. The causes range from genetic, anatomical, and endocrine to constitutional delay. A stepwise diagnostic approach is key to guiding appropriate investigations whilst minimising the physical and psychological impact on young adolescent women.     

Management of Asherman's syndrome

Intrauterine adhesions (IUA) or Asherman's syndrome is a multifaceted condition which is being diagnosed with increasing frequency. Although it usually occurs following curettage of the pregnant or recently pregnant uterus, any uterine surgery can lead to IUA. Most women with IUA have amenorrhoea or hypomenorrhoea, but some have normal menses. Those who have amenorrhoea may also have cyclic pelvic pain secondary to 'trapped' menses and the accompanying retrograde menstruation may lead to endometriosis. In addition to menstrual disorders, most women with IUA will present with infertility or recurrent spontaneous abortion. Over the last four decades hysteroscopy has become the standard method to diagnose and treat this condition. Various techniques for adhesiolysis and for prevention of scar reformation have been advocated. The most efficacious appears to be the use of miniature scissors for adhesiolysis and the placement of a balloon stent inside the uterus immediately after surgery. Post-operative oestrogen therapy is prescribed in order to stimulate endometrial regrowth. Follow-up studies to assure resolution of the IUA are mandatory before the patient attempts to conceive as is careful monitoring of pregnancies for cervical incompetence, placenta accreta and intrauterine growth restriction.     

Delayed puberty with extreme uterine hypotrophy: do not conclude too early to the absence of the uterus

OBJECTIVE: To emphasize the difficulties to distinguish between uterine agenesis and extreme uterine hypotrophy in the context of primary amenorrhoea with delayed puberty. PATIENTS AND METHODS: Among adolescents who consulted with our center because of primary amenorrhoea, from 1997 to 2005, three patients were referred for a suspicion of Mayer-Rokitansky-Kuster-Hauser Syndrome, after ultrasonography had failed to visualize the uterus. The 3 patients underwent endocrine and genetic evaluations. Transabdominal ultrasonography and MRI performed pelvic examination. Patients were placed under estrogen treatment. RESULTS: Endocrine evaluation indicated primary ovarian failure for patient 1, and hypogonadotrophic hypogonadism for patients 2 and 3. Karyotype was 46,XX in all patients. Initial pelvic ultrasonography revealed the absence of uterus. MRI allowed visualizing prepubertal uterus for patient 1, a hypotrophic uterus for patient 3 and concluded to uterine agenesis for patient 2. In all cases estradiol substitutive therapy induced uterine growth and confirmed retrospectively the diagnosis of extreme uterine hypotrophy. DISCUSSION AND CONCLUSION: Pelvic ultrasonography can be misleading in the evaluation of primary amenorrhoea. No visualization of uterus on ultrasonography can occur in the context of delayed puberty and should not induce a premature diagnosis of Mayer-Rokitansky-Kuster-Hauser syndrome. Indeed, such a diagnosis has therapeutic, reproductive and psychological consequences.     

Resistant ovary syndrome. Case report

Patients with primary amenorrhea, sexual infantilism and elevated pituitary gonadotropins are frequently diagnosed with hypogonadism hypergonadotropic and suspected ovarian failure, secondary to a chromosomal abnormality, intrinsic ovarian failure or altered receptors for gonadotropins, mainly FSH (ovarian resistance). We report the case of a 16-year-old, admitted to the endocrinology clinic for primary amenorrhea and lack of development of secondary sexual characteristics. A complete physical examination revealed: height of 1.58 m and 57 kg weight, with incipient breasts (Tanner I), sparse pubic and axillary hair (Tanner I). The ultrasound reported small uterus and ovaries. Laboratory studies reported high levels of FSH and LH, estradiol and testosterone levels before puberty, prolactin, TSH, T3 and T4 normal. Normal female karyotype. Diagnostic laparoscopy was performed which showed two ovarian slips; biopsy was taken and reported both abundant primordial follicles and spindle cell stroma without evidence of primary and antral follicles, which integrates the diagnosis of resistant ovary syndrome.     

Reduced spinal bone density in young women with amenorrhoea.

To assess the influence of diminished oestrogen production on bone density, we studied 23 amenorrhoeic women and 20 controls (age range 16-29 years) divided into four groups: group 1: 6 patients with idopathic hypogonadotrophic hypogonadism with primary amenorrhoea (IHH); group 2: 5 patients with delayed puberty owing to thalassaemia major (TM); group 3: 12 patients with secondary hypothalamic amenorrhoea (HA); group 4: 20 women with normal menses (controls). Secondary sexual characteristics had developed in all except the women with TM. Groups 1 and 2 had never menstruated and group 3 had been amenorrhoeic for 6 months to 3 years. The control group was studied during the follicular phase of the cycle. None of the patients were taking oestrogens at the time of observation. Plasma concentrations were determined for 17 beta-oestradiol (E2), deidroepiandrosterone sulphate (DHEA-S), cortisol (F), prolactin (PRL), thyroid hormones (T3 and T4), and gonadotrophins (LH and FSH). Spinal bone mineral density (BMD g/cm2) was assessed by dual photon absorbiometry. BMD (mean +/- 1SD) was reduced in the patients (group 2: 0.920 +/- 0.95; group 1: 0.980 +/- 0.94; and group 3: 1.037 +/- 0.75) as compared with the controls (1.290 +/- 0.95) (P less than 0.01). In the three groups of patients, plasma E2 levels were lower than 50 pg/ml and were positively correlated with the BMD. As expected, plasma gonadotrophin levels were highly and significantly reduced (P less than 0.01) in the patients, compared with that of the controls. These results suggest that reduced spinal BMD in hypogonadic women may be related to the lack of oestrogenic influence on bone metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevalence of chromosomal aberrations in Mexican women with primary amenorrhoea

Primary amenorrhoea refers to the absence of menarche by the age of 16-18 years in the presence of secondary sexual characteristics, and occurs in 1-3% of women of reproductive age. To study the prevalence of chromosomal abnormalities and the different options available for clinical management of women in Mexico with primary amenorrhoea, a cross-sectional study was conducted in 187 women with primary amenorrhoea referred from Department of Reproductive Medicine of Morones Prieto Hospital, IMSS in Monterrey, Mexico during 1995-2003. Peripheral blood lymphocytes were cultured for chromosomal studies by the standard methods. Numerical or structural abnormalities of the sex chromosome were found in 78 women (41.71%). These women were classified into four categories: X-chromosome aneuploidies (22.99%: 12.83% pure line and 10.16% mosaicism association with a 45, X cell line); presence of chromosome Y (10.70%); structural anomalies of the X chromosome (4.28%); and marker chromosomes (3.74%). In conclusion, the prevalence of chromosomal abnormalities in Mexican women with primary amenorrhoea is within the range (24-46%) reported in world literature. Chromosomal analysis is absolutely necessary for appropriate clinical management of these patients.     

Hypothalamic disease presenting as amenorrhoea: value of computed tomography

Five women presenting with amenorrhoea (three with secondary amenorrhoea and galactorrhoea, and two with primary amenorrhoea) were shown to have suprasellar abnormalities by computed tomography. Organic hypothalamic disease was confirmed at surgery (craniopharyngioma in three, intra- and suprasellar Rathke's cleft cyst in one, aqueductal stenosis and suprasellar arachnoid cyst in one). Moderate hyperprolactinaemia was present in the first four, while the last had isolated gonadotrophin deficiency of hypothalamic origin. One of the hyperprolactinaemic women had entirely normal residual pituitary function, visual fields and tomography of the sella. Two of the patients with secondary amenorrhoea and galactorrhoea had resumption of menses during bromocriptine therapy before operation. Spontaneous menarche and subsequent pregnancy occurred after ventriculoatrial shunt in the girl with aqueductal stenosis. Organic hypothalamic diseases may present with amenorrhoea (sometimes as the only symptom) more commonly than previously appreciated. Computed tomography should replace conventional tomography of the sella and should be an essential part of the clinical investigation in all patients with amenorrhoea of hypothalamo-pituitary origin.     

Hypothalamic disease presenting as amenorrhoea: value of computed tomography

Summary. Five women presenting with amenorrhoea (three with secondary amenorrhoea and galactorrhoea, and two with primary amenorrhoea) were shown to have suprasellar abnormalities by computed tomography. Organic hypothalamic disease was confirmed at surgery (craniopharyngioma in three, intra- and suprasellar Rathke's cleft cyst in one, aqueductal stenosis and suprasellar arachnoid cyst in one). Moderate hyperprolactinaemia was present in the first four, while the last had isolated gonadotrophin deficiency of hypothalamic origin. One o f the hyperprolactinaemic women had entirely normal residual pituitary function, visual fields and tomography of the sella. Two of the patient, with secondary amenorrhoea and galactorrhoea had resumption of menses during bromocriptine therapy before operation. Spontaneous menarche and subsequent pregnancy occurred after ventriculoatrial shunt in the girl with aqueduetal stenosis. Organic hypothalamic diseases may present with amenorrhoea (sometimes as the only symptom) more commonly than previously appreciated. Computed tomography should replace conventional tomography of the sella and should be an essential part of the clinical investigation in all patients with amenorrhoea of hypothalamo-pituitary origin.     

Irregular or absent periods--what can an ultrasound scan tell you?

Transvaginal ultrasonography has increased our appreciation of the physiological changes in the ovary and endometrium that occur during the normal menstrual cycle. It has become a primary investigative tool in women with irregular or absent periods. Its usefulness in cases of primary amenorrhoea to assess anatomy is also undisputed although it may have limitations in terms of its specificity. However, the interpretation of ultrasound images in women with irregular menses or secondary amenorrhoea is not entirely straightforward. This is particularly true in the diagnosis of polycystic ovary syndrome, a condition of uncertain aetiology, which may present with oligoamenorrhoea. This chapter aims to discuss the benefits and limitations of ultrasound while taking into account the broad overlap between normal and abnormal physiology, some of which has still to be elucidated.     

Risk Factors Associated with Primary and Secondary Reduced Libido in Male Patients with Sexual Dysfunction

IntroductionHypoactive sexual desire is defined as a persistent or recurrent deficient or absent sexual fantasies or desire for sexual activity that should not be comorbid with other medical conditions or with the use of psychoactive medications. Reduced libido is a symptom referring more to a reduction in sexual drive for sexual activity.AimTo investigate the risk factors of primary reduced libido (i.e., not associated with conditions causing loss of libido such as hypogonadism, hyperprolactinemia, psychopathology, and/or psychoactive medications) or secondary reduced libido (i.e., with aforementioned conditions) in male patients with sexual dysfunction.MethodA consecutive series of 3,714 men (mean age 53.2 ± 12.5 years) was retrospectively studied.Main Outcome MeasuresPatient's reduced libido was evaluated using question #14 of structured interview for erectile dysfunction (SIEDY) (“Did you have more or less desire to make love in the last 3 months?”).ResultsReduced libido was comorbid with erectile dysfunction, premature ejaculation, and delayed ejaculation in 38%, 28.2%, and 50%, respectively, whereas it was isolated in 5.1%. Reduced libido prevalence was substantially increased by hypogonadism, almost doubled by psychopathology and universally present in subjects with hyperprolactinemia (secondary reduced libido). Subjects with primary reduced libido are characterized by higher postschool qualification, more disturbances in domestic and dyadic relationships, and an overall healthy body (lower glycemia and triglyceride levels). Accordingly, in patients with primary reduced libido, the risk of major cardiovascular events as calculated with the Progetto Cuore algorithm was lower than in the rest of the sample. Features of hypogonadism‐ or psychopathology‐associated reduced libido essentially reflect their underlying conditions. Comorbidity with other sexual dysfunctions did not affect the main characteristics of primary or secondary reduced libido.ConclusionsPrimary and secondary reduced libido have different risk factors and clinical characteristics. Recognizing primary or secondary reduced libido will help clinicians to identify comorbidities and to tailor appropriate treatments.     

闭经

闭经指育龄期妇女月经未来潮。导致闭经的病因很多,有病理性和生理性两类。病理性原因导致的闭经多见于原发性闭经,解剖原因所致的闭经少见但也很重要。妊娠和哺乳期闭经属生理性闭经。闭经通常分为原发性和继发性闭经两种。原发性闭经指16岁时仍无月经来潮,而继发性闭经是指≥6个月无月经来潮。导致闭经原因常常多个混杂,所以区别两者的实际意义不大。导致闭经的内分泌因素包括:多囊卵巢综合征、紧张和劳累、体重相关、高泌乳素血症、心理性疾病、全身性疾病如:肾功能衰竭、药物因素、卵巢早衰、垂体缺血性坏死、原发性下丘脑-垂体-卵巢(H…     

Body weight, exercise and menstrual status among ballet dancers in training

Summary. A prospective study of the menstrual pattern and weight changes was made in the first year of training of 29 new female entrants to a professional ballet school. Seventy-nine per cent of the student girls had menstrual disturbances at entry: primary amenorrhoea, four; secondary amenorrhoea, 11; irregular menses, eight. The incidence of secondary amenorrhoea increase substantially by the end of the year (20), but was not associated with any significant change in body weight. Only three students menstruated regularly during the year. Menstrual regularity improved during periods of injury and long vacation and it appears that deterioration of the menstrual pattern during dancing periods was related to strenuous physical exercise rather than to any change in body weight.     

Secondary amenorrhea with normal ovulatory cycles in a young virgin with normal follicle stimulating hormone levels--a case report

PURPOSE: To determine if normal ovulation is possible despite amenorrhea in the absence of any obvious uterine abnormalities or adhesions. METHODS: The study was conducted on a 17-year-old virgin with normal sexual development and normal secondary sexual characteristics whose menarche was at age 12 but whose menses ceased after two menstruations. She was first treated with medroxyprogesterone acetate 10 mg x ten days and then a cycle of oral contraceptives. RESULTS: She failed to get menses following progesterone (P) withdrawal and following a cycle of oral contraceptives. All of her pituitary function studies were normal. Her serum follicle stimulating hormone (FSH) was 3 mIU/ml, luteinizing hormone (LH) 9 mIU/ml, estradiol (E2) was 107 pg/ml and the serum P was 3.9 ng/ml. These values were consistent with recent ovulation. However menses failed to ensue. CONCLUSIONS: This case confirms that in humans, similar to some non-primates, ovulation is possible without shedding the endometrium. Possibly she lacked spiral arterioles similar to ovulating mammals. Her virginal introitus and lack of any serious febrile illness made Asherman's syndrome highly unlikely. Her normal menstrual cycle at age 12 not only excluded a mullerian abnormality or imperforate hymen but led to speculation as to whether anovulatory bleeding from unopposed estrogen was possible but that somehow the presence of P inhibited the endometrial shedding process. In contrast to a previously reported study, this young woman almost had primary amenorrhea whereas the former case had more menses during her life but they ceased shortly after age 30.     

Störungen der Geschlechtsentwicklung

Disorders of sex development (DSD) were previously termed “intersexuality”. They comprise inborn errors of genetic control of the sexual determination of the gonads and of hormonal control of sexual differentiation of the genitalia. Among the endocrine mechanisms the presence or absence of normal androgen biosynthesis and androgen action plays a central role. Disorders of sex development can be part of overriding syndromes. In Germany the incidence is approximately 1 in 4,500 newborns. Clinically, disorders of sex development are mostly diagnosed at birth because of ambiguities of the external genitalia. However, they can be present in cases of primary amenorrhoea, virilization of a girl at pubertal age or even in cases of an abdominal tumor (dysgerminoma). Disorders of sex development can be associated with developmental and functional disorders of the kidneys and the adrenal glands.     

Primary amenorrhoea caused by congenital absence of the uterus

The authors discuss the case of a 21-year-old female of Afro-Caribbean origin, who presented with primary amenorrhoea, and was found to have congenital absence of the uterus and fallopian tubes in the presence of a normal vaginal cavity.     

Secondary amenorrhoea: prevalence and medical contact--a cross-sectional study from a Danish county.

OBJECTIVE: To examine the prevalence of secondary amenorrhoea and the patterns of seeking medical advice for secondary amenorrhoea in an unselected population. DESIGN: Cross-sectional postal questionnaire study. SETTING: County of Copenhagen, Denmark. SUBJECTS: 3743 women, aged 15-44, selected at random from a Danish county who were asked to provide information on menstrual patterns for the preceding year, 1988. The response rate was 78%. Information from non-responders was obtained via telephone interviews. RESULTS: One-year period prevalence of secondary amenorrhoea of more than 3 months duration was 4.6% and was 7.6%, 3.0%, and 3.7% in women aged 15-24, 25-34, and 35-44 respectively. The duration of secondary amenorrhoea was 6 months or less in 75% aged 15-34 years, but longer than 6 months in 55% of those aged 35-44 years. A social gradient was found of the prevalence of secondary amenorrhoea (odds ratio 3.3, 95% CI 1.5-8.3) in the lowest social group compared with the highest social group; controlled by age. Only 39% of women with secondary amenorrhoea had contacted a doctor. Educational level or social status did not seem to influence the frequency of medical contact in women with amenorrhoea. CONCLUSION: Spontaneous return of the menstrual cycle occurs within 6 months in many amenorrheic women below the age of 35. The detailed investigation of secondary amenorrhoea in this age group can be postponed until it is of 6 months duration, unless there is clinical suspicion of disease. The relative infrequency with which women with secondary amenorrhoea seek medical advice constitutes an important source of selection bias in hospital-based clinical research on this topic.     

Thalassemia and infertility

Beta-thalassemia (BTM) major is the most common haemoglobin disorder in the world, with high prevalence in people of Mediterranean, Arab or Asian origin. It has been estimated that about 1.5% of the global population (80–90 million people) are carriers of BTM. In patients with BTM, long-term transfusion therapy for the correction of anaemia leads to toxic iron overload, resulting in significant morbidity including liver damage, cardiac complications and endocrine dysfunction. The commonest abnormality is hypogonadotropic hypogonadism, which presents with primary amenorrhoea, delayed puberty or secondary amenorrhoea with consequent infertility. Nevertheless, current improvements in the management of thalassemia disorders offer patients the possibility of having a regularly functioning reproductive system and increased chances of achieving a pregnancy. The aim of the present review is to analyse all aspects of fertility management in BTM women, by examining the main causes of infertility, in order to give practical tools to ensure a complete diagnostic work-up and discuss intervention options to guarantee maximum reproductive health.     

Síndrome de Youssef y fístulas vesicouterinas

Youssef's syndrome is a rare complication commonly secondary to lower segment caesarean section. It consists of a vesicouterine fistula situated above the isthmus of the uterus. Its symptomatology is analysed, which includes the classical triad of caesarean section, amenorrhoea and cyclic haematuria or menurias in the absence of urinary incontinence, together with its diagnosis and treatment, usually surgical, with excision of its fistulous tract and interposition of an omental pedicle.     

Women with hypogonadotropic hypogonadism: cycle characteristics and results of assisted reproductive techniques

OBJECTIVE: To present cycle characteristics and results of in vitro fertilization in 27 patients with hypogonadotropic hypogonadism. Further, to demonstrate the consequences of advanced age (> or =35 years). METHODS: Data from 27 hypogonadotropic hypogonadism patients treated with in vitro fertilization in the period from 2000 to 2004 were analyzed and compared with treatment results from 39 patients with unexplained infertility. Moreover, data from hypogonadotropic hypogonadism patients were analyzed according to the age factor. Mann-Whitney U, Chi-square, and Student's t-tests were used for statistical analysis. p<0.05 was considered significant. RESULTS: Higher gonadotropin consumption and a longer stimulation period were observed in the hypogonadotropic hypogonadism group. Peak E2 levels, and the total number of oocytes and metaphase II oocytes were higher in the unexplained infertility group. Although a higher number of grade I embryos were transferred in the unexplained infertility group, the implantation rate was found to be better in the hypogonadotropic hypogonadism group (36.5% versus 13%; p<0.0001). Pregnancy rates were similar. When hypogonadotropic hypogonadism patients were evaluated according to the age factor, no significant difference was found with regard to cycle and outcome parameters, except higher gonadotropin consumption in aged patients. In aged hypogonadotropic hypogonadism patients, a pregnancy rate of 50% was achieved. CONCLUSION: Hypogonadotropic hypogonadism women undergoing in vitro fertilization were found to be good responders. In the presence of advanced age, management of these patients becomes challenging. However, even these patients still have a good chance of pregnancy.     

Primary amenorrhoea

Puberty transforms a girl into a fertile woman, and its social importance is so great that any deviation from normality may be the cause of considerable embarrassment and anxiety. Delayed puberty in girls is defined as the absence of physical manifestations of puberty by the age of 13 years. Primary amenorrhoea is the absence of menarche and needs to be evaluated in the context of secondary sexual characteristics. Differential diagnoses can be classified according to the level of gonadotrophins. Differences in Sex Development and Complex Obstructed Mullerian Duct Anomalies should be investigated and managed in a specialist centre within a multidisciplinary team. Psychological support is essential.