Resección laparoscópica de un tumor virilizante suprarrenal derecho / Laparoscopic approach in an adrenal right virilizing tumour

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A genetic risk score is associated with polycystic ovary syndrome-related traits.

STUDY QUESTION: Is a genetic risk score (GRS) associated with polycystic ovary syndrome (PCOS) and its related clinical features? SUMMARY ANSWER: The GRS calculated by genome-wide association studies (GWASs) was significantly associated with PCOS status and its related clinical features. WHAT IS KNOWN ALREADY: PCOS is a heterogeneous disorder and is characterized by oligomenorrhea, hyperandrogenism and polycystic ovary morphology. Although recent GWASs have identified multiple genes associated with PCOS, a comprehensive genetic risk study of these loci with PCOS and related traits (e.g. free testosterone, menstruation number/year and ovarian morphology) has not been performed. STUDY DESIGN, SIZE, DURATION: This study was designed as a cross-sectional case-control study. We recruited 862 women with PCOS and 860 controls. Women with PCOS were divided into four subgroups: (1) oligomenorrhea + hyperandrogenism + polycystic ovary, (2) oligomenorrhea + hyperandrogenism, (3) oligomenorrhea + polycystic ovary and (4) hyperandrogenism + polycystic ovary. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Genomic DNA was genotyped for the PCOS susceptibility loci using the HumanOmni1-Quad v1 array. Venous blood was drawn in the early follicular phase to measure baseline metabolic and hormonal parameters. A GRS was calculated by summing the number of risk alleles from 11 single-nucleotide polymorphisms (SNPs) that were identified in previous GWASs on PCOS. A weighted GRS (wGRS) was calculated by multiplying the number of risk alleles for each SNP by its estimated effect (beta) obtained from the association analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The GRS was higher in women with PCOS than in controls (8.8 versus 8.2, P < 0.01) and was significantly associated with PCOS after adjusting for age and BMI. An analysis of GRS quartiles (Q1 = 3-5, Q2 = 6-8, Q3 = 9-11, Q4 = 12-15) revealed that the subjects in the highest quartile showed a remarkable increased risk of PCOS compared with those in the lowest quartile (odds ratio = 6.28, P < 0.001). Free testosterone level, menstruation number per year, ovarian volume and ovarian follicle numbers were significantly associated with the GRS (in all cases, P < 0.01). The wGRS yielded similar results. LIMITATIONS, REASONS FOR CAUTION: We used 11 loci for the calculation of GRS, but a higher number of PCOS risk alleles was reported in previous studies. Therefore, further studies should assess the value of GRS including the additional SNPs related to PCOS. Although a GRS of ≥12 was significantly associated with PCOS, the GRS showed a poor predictive value; therefore, the use of genetic information based on current GWAS data only may present problems. WIDER IMPLICATIONS OF THE FINDINGS: The GRS could be used to identify asymptomatic individuals among people at risk and stratify them into accurate risk categories for the purpose of individualizing treatment approaches, which could potentially improve health outcomes. STUDY FUNDING/COMPETING INTERESTS: None of the authors have any conflicts of interest to declare. No funding was obtained for the study.

[RISK FACTORS AND CLINICAL PECULIARITIES OF SECONDARY OLIGOMENORRHEA IN ADOLESCENT GIRLS].

Risk factors related to secondary oligomenorrhea (SOM) are the presence of chronic extragenital pathology, abrupt changes in body mass during a short period of time, a burdened perinatal history at the onset of SOM after a year of regular menstruations. Adolescent girls with SOM differ from their healthy peers by a frequent occurrence of hirsutism, obesity and body mass deficit, uterine hypoplasia.

Clinical pattern and spectrum of endometrial pathologies in patients with abnormal uterine bleeding in Pakistan: need to adopt a more conservative approach to treatment.

BACKGROUND: Abnormal uterine bleeding (AUB) is one of the most common debilitating menstrual problems and has remained one of the most frequent indications for hysterectomy in developing countries. Approximately in 40% of hysterectomy specimens, no definite organic pathology could be established. The problem is common worldwide but causes may vary from one region to another. This study may help gynecologists in our population to improve their therapeutic strategies by promoting minimally invasive uterus sparing modalities such as endometrial ablation and hysteroscopic resection of early proliferative lesions. METHODS: It was a prospective, cross-sectional study conducted at Liaquat National Hospital from 15(th) January 2010 till 14(th) July 2011 over a period of 18 months. Women who underwent dilatation and curettage for endometrial sampling with complaints of AUB were included in the study and histopathologic spectrum was determined. RESULTS: Polymenorrhea was the most common presenting pattern (30%, 72/241) with reproductive age women being the most susceptible (49.3%,119/241). The commonest histopathological spectrum was normal menstrual pattern (34%, 82/241) and the commonest pathology was hormonal imbalance (27%, 65/241), followed by endometrial polyp (14%, 34/241), chronic endometritis (12%, 28/241), atrophic endometrium (6%, 15/241), endometrial hyperplasia (5%, 12/241), and endometrial carcinoma (2%, 5/241). Chronic endometritis was commonly seen in reproductive age (18%, 21/119); hormonal imbalance (45%, 35/77) and endometrial hyperplasia (6.5%, 5/77) in perimenopausal age; endometrial polyp (35.5%, 16/45) and endometrial carcinoma (9%, 4/45) in postmenopausal age. CONCLUSION: Frequency of benign endometrial pathology is quite high in AUB, 236 participants (98%, 236/241). Histopathological spectrum in patients with AUB is quite variable with respect to age. The most common pattern of AUB was polymenorrhea. The most common pathology was hormonal imbalance. It is suggested that age was associated with more progressive lesions found in peri and postmenopausal age group such as endometrial hyperplasia and endometrial carcinoma. Yet endometrial polyp was the most common pathology found in postmenopausal women. Therefore, the management strategy should be individualized, as in most cases a restrictive approach is appropriate in order to avoid unnecessary hysterectomies.

[Evaluation of endometrial histologic morphology in patients with polycystic ovary syndrome]. / Ocena obrazów morfologicznych endometrium u pacjentek z zespolem policystycznych jajników.

AIM: To evaluate endometrial histologic morphology in patients with polycystic ovary syndrome. MATERIAL AND METHODS: 93 women, aged 18-35, who were hospitalized in the Gynaecologic Endocrinology Department of Warsaw Medical University due to PCOS have been qualified for the research. All patients had menstrual pattern of oligomenorrhoea and mean cycle length of 49 +/- 38 days. The control group consisted of 40 healthy women with regular menstrual cycles and no symptoms of hyperandrogenism. In case of each patient the fallowing data were analyzed: age, menarche age Body Mass Index and endometrium histologic findings. The endometrium was aspirated using the Pipelle probe. Statistic analysis was performed and the values of p < 0.05 were deemed statistically significant. RESULTS: No statistical significance was found between the age of the patients, their menarche age and BMI. Proliferative endometrium was significantly more often observed (p < 0.01) in patients with PCOS (64.52%) than in the control group (15%). Secretory endometrium was found in 23.65% of the examined patients. This result differed statistically from the 85% rate in the control group (p < 0.01). In case of PCOS patients, mixed type endometrium was found in 10 patients (10.75%) and simple endometrial hyperplasia without atypia was found in 1 patient (1.08%). CONCLUSIONS: (1) Lack of ovulation or late ovulation play a crucial role in endometrial cyclic transformation and its disorders. (2) The prolonged endometrial proliferation phase is a characteristic feature of women suffering from PCOS.

Formation and early development of follicles in the polycystic ovary.

BACKGROUND: Polycystic ovary syndrome is the most common cause of anovulatory infertility. It has long-term health implications and is an important risk factor for type 2 diabetes. However, little is known about the cause of polycystic ovaries. We have used detailed morphological analysis to assess the hypothesis that there is an intrinsic ovarian abnormality that affects the earliest stages of follicular development. METHODS: We took small cortical biopsies during routine laparoscopy from 24 women with normal ovaries and regular cycles and from 32 women with polycystic ovaries, 16 of whom had regular, ovulatory cycles and 16 of whom had oligomenorrhoea. We used computerised image analysis to assess the density and developmental stage of small preantral follicles in serial sections of fixed tissue. FINDINGS: Median density of small preantral follicles, including those at primordial and primary stages, was six-fold greater in biopsies from polycystic ovaries in anovulatory women than in normal ovaries (p=0.009). In both ovulatory and anovulatory women with polycystic ovaries, we noted a significant increase in the percentage of early growing (primary) follicles and a reciprocal decrease in the proportion of primordial follicles compared with normal ovaries. INTERPRETATION: Our findings indicate that there are fundamental differences between polycystic and normal ovaries in early follicular development, suggesting an intrinsic ovarian abnormality. The increased density of small preantral follicles in polycystic ovaries could result from increased population of the fetal ovary by germ cells, or from decreased rate of loss of oocytes during late gestation, childhood, and puberty.

Hormonal profile of women with self-reported symptoms of oligomenorrhea and/or hirsutism: Northern Finland birth cohort 1966 study.

The hormonal profiles of nested female patients (n = 500) with self-reported symptoms typical of polycystic ovary syndrome (PCOS), oligomenorrhea, and/or hirsutism and their randomly selected controls (n = 1026) at the age of 31 yr were analyzed in a general population-based Northern Finland birth cohort 1966 to find out whether the symptomatic women also have the endocrine characteristics of PCOS and could be detected in a general population using simple questions. Higher medians of serum testosterone (T) (2.10 vs. 1.90 nmol/liter, P < 0.001), LH (5.40 vs. 4.85 U/liter, P = 0.005), insulin (53.8 vs. 51.66 pmol/liter, P = 0.040), and free androgen index (FAI) (4.01 vs. 3.03, P < 0.001) and lower glucose/insulin ratio (91.1 x 10(8) vs. 94.9 x 10(8), P = 0.048) and SHBG (52.4 vs. 60.7 nmol/liter, P < 0.001) were observed among the cases, but no difference was observed in cortisol and glucose levels between the cases and controls. Of all the women in the cohort, 10.2% reported only oligomenorrhea and had biochemical findings similar to the whole case group. Those who reported only hirsutism (10.4%) were in between the case and control groups according to biochemical findings. The subjects who reported both oligomenorrhea and hirsutism (3.4%) had the highest T, LH, FAI, insulin, and glucose and the lowest SHBG and glucose/insulin ratio, compared with the case group and the groups with either symptom only indicating a dose-response manner in typical endocrine profile of PCOS by adding up symptoms. The levels of T and FAI were higher and SHBG lower in groups with overweight or obesity both at 14 and 31 yr, compared with groups with normal weight at 14 yr and overweight or obesity at 31 yr. In the group with normal weight at 14 and 31 yr and the group with overweight or obesity at 14 yr but normal weight at 31 yr, the levels of T and FAI were lowest and SHBG highest. T and FAI were higher and SHBG lower among the cases than the controls in groups stratified by weight development from adolescence to adulthood. In conclusion, this longitudinal study of a large, stable population indicates that women with self-reported symptoms of hirsutism and/or oligomenorrhea show endocrine characteristics of PCOS and can be detected in a general population using simple questions. These symptoms are markers of the underlying metabolic alterations possibly associated with increased health risks in later life.

Oligo-amenorrheic long-distance runners may lose more bone in spine than in femur.

PURPOSE: Strenuous training can be associated with amenorrhea leading to amenorrhea-related accelerated bone loss. Insufficient calorie energy, calcium, and/or protein intakes can also be frequently encountered in women with intense training, possibly contributing to bone loss. Long-distance runners with or without regular menses (age range 19-37 yr) were prospectively studied. METHODS: Changes in areal bone mineral density (BMD) were measured at 1-yr interval. RESULTS: Among 10 eumenorrheic, 11 oligo-amenorrheic, and 9 oral contraceptive users, there was no difference in energy, calcium, or protein intakes. Baseline BMD values were significantly lower in the oligo-amenorrheic group than in the two others at the level of lumbar spine (anteroposterior view: 0.941+/-0.039 in oligo-amenorrheic vs 1.077+/-0.029 or 1.051 +/-0.017 g x cm(-2), P < 0.005, in the eumenorrheic and contraceptive user groups, respectively) but not in weight-bearing bone such as proximal and midshaft femur. Over a 1-yr interval, during which the three groups did not differ in terms of running distances and dietary intakes, oligo-amenorrheic women displayed a significant decrease in lumbar spine BMD in lateral view (-0.049+/-0.012 in oligo-amenorrheic vs -0.001+/-0.013 and 0.014+/-0.012 g x cm(-2), p < 0.005, in the eumenorrheic and contraceptive user groups, respectively). We did not detect any significant change in femoral neck, trochanter, or midshaft BMD. CONCLUSIONS: Oligo-amenorrhea in long-distance runners, with adequate dietary intakes, was associated with a decrease in BMD affecting more the lumbar spine than the proximal and midshaft femur during a 1-yr follow-up.

Alteraciones del ciclo menstrual en internas y residentes / Menstrual cycle charges in interns and residents

Determinar la incidencia de trastornos menstruales en internas y residentes asistenciales y de posgrado. Se entrevistaron las médicas utilizando un cuestionario elaborado para tal efecto. Hospital de la ciudad de Maracaibo tipo 3 y 2. Se analizaron 207 cuestionarios (87,7 por ciento) de 236 entrevistas: 172 (83,1 por ciento) residentes y 41 (16,9 por ciento) internas. Cincuenta y seis casos (27,15 por ciento) presentaron trastornos menstruales. La alteración del ciclo menstrual más frecuente fue el acortamiento de los mismos. El hospital, tipo de especialidad y año de residencia no tuvieron influencia. Las causas psíquicas fueron las que ocasionaron mayor número de alteraciones menstruales (84,5 por ciento) y al ser comparadas con causas de otro origen (15,5 por ciento) se encontró diferencia estadísticamente significativa (p=0,003). Las guardias fueron referidas como la causa más frecuente de irregularidad del ciclo (22,7 por ciento). Las médicas representan un grupo poblacional de alto riesgo a presentar alteraciones en el ciclo menstrual por su exposición a estrés psíquico

[The effect of neoplastic hyperprolactinemia on bone density]. / Ruolo dell'iperprolattinemia tumorale sulla densità ossea.

In young hyperprolactinaemic patients a reduction of bone mass density is frequently shown. However, until now the real mechanism has not been clarified (a direct role of PRL has been suggested). To better clarify the origin of the bone demineralization during hyperprolactinaemia we evaluated the BMD in a group of 24 proved PRL secreting pituitary adenomas. Based on menstrual characteristics the patients were subdivided in 3 groups: 1) oligomenorrhoea (OM), 2) amenorrhea lasting less than 2 years (AMa), 3) long-lasting amenorrhea (AMb). Twelve women with normal menstrual cycles served as controls. The BMD values at L2-L4 and thighbone levels were significantly reduced in the AMb group with respect to the other subgroups. The results support the hypothesis that BMD reduction in aPRL patients is secondary to hypoestrogenism and to the duration of amenorrhea rather than to hyperprolactinaemia.

Collegiate women athletes with irregular menses during adolescence have decreased bone density.

We studied six eumenorrheic and 13 oligomenorrheic collegiate women athletes who were matched in all respects other than menstrual histories. There was a significant (P less than .05) association between menstrual regularity and bone density. The severely oligomenorrheic subjects had modestly decreased plasma estrogen levels. These findings support the notion that plasma estrogen levels during adolescence play a significant role in the development of peak adult bone density in women.

Use of immunocytochemistry of progesterone and estrogen receptors for endometrial dating.

Endometrial progesterone and estrogen receptors were studied by immunocytochemistry using monoclonal antibodies during the menstrual cycle in normal women. We initially compared immunocytochemical staining of progesterone and estradiol receptors on endometrial fragments obtained by either aspiration or endometrial biopsy and found that immunocytochemistry could be performed easily on tissue obtained in either way. The immunocytochemical studies showed that the concentration and distribution of receptors changed markedly during the normal menstrual cycle. These changes were distributed in three characteristic phases. During phase I, corresponding to the midfollicular period (days 7-8), a small proportion (25%) of stromal and glandular cells stained positively for the progesterone receptor, whereas estrogen receptor staining was more intense and more frequent (50% of cells). Phase II, which included both the late follicular and early luteal periods (days 9-19), was characterized by a marked staining of progesterone receptors in the majority of glandular cells (75%) and somewhat less abundant and less frequent staining in stromal cells (50%). Estrogen receptor staining was present in about half of the glandular and stromal cells. Phase III, the mid- and late luteal period (days 21-27), was characterized by the disappearance of estrogen and progesterone receptor staining in glandular cells, although faint staining for both receptors was found in stromal cells. These variations in progesterone receptor staining are potentially useful for determining the effect of progesterone on endometrial maturation.

Ultrasonographic study of ovaries of 19 women with weight loss-related hypothalamic oligo-amenorrhea.

A study of 19 nonhirsute women with weight loss-related hypothalamic oligo-amenorrhea revealed evidence of multifollicular ovaries in 17. Enlarged ovaries greater than 10 cm3 were found in 8 of these subjects (42.1%). High-resolution real-time ultrasonography of the pelvis of 19 weight loss-related oligo-amenorrheic subjects revealed a mean +/- SD maximum ovarian volume (MOV) of 11.8 +/- 7.0 cm3, which was significantly different from those of control subjects whose mean +/- SD MOV was 5.2 +/- 1.9 cm3 (P = less than 0.001). The data do not allow a specific ultrasonographic distinction between hyperandrogenic women with polycystic ovarian disease and women with weight loss-related hypothalamic amenorrhea.

Hysteroscopic evaluation and endocrinological aspects of women with müllerian anomalies and oligomenorrhea.

In a prospective study of 28 consecutive patients with oligomenorrhea, two had uterus didelphys, and the incidence of mild müllerian anomalies was 50.0%, assessed by hysterosalpingography (HSG). The objects of the study were (1) to confirm these müllerian anomalies hysteroscopically, (2) to assess the predictive value of an abnormal and a normal fundal contour on the HSG, and (3) to find anamnestic, chromosomal, or hormonal characteristics, if any, for women with oligomenorrhea and müllerian anomalies. Twelve patients underwent HSG followed by hysteroscopy, at which a septum or fundal convexity was confirmed in six out of seven patients in whom HSG had shown a mild to moderate indentation of the fundus, but showed no such sign in any of the five patients in the control group in whom the uterine contours had been normal on the HSG (P less than .01). There were no evident anamnestic, chromosomal, or hormonal characteristics for women having uterine developmental anomalies and oligomenorrhea, but there was a major or minor shift in certain androgenic metabolites in some of the patients in this group. It is concluded that HSG seems of great value in diagnosing uterine septa, but hysteroscopy afforded more precise information concerning the degree of fundal anomaly. Longitudinal, more standardized studies are needed for further elucidation of the etiology of the oligomenorrhea in these patients.

Clinicopathologic investigation of ovarian endometriosis: a comparative study of cystic and non-cystic types.

This clinicopathologic study involved 129 patients with ovarian endometriosis. All the lesions from the patients were classified macroscopically into two types being either cystic or non-cystic. The results are as follows. Endometriotic lesions were bilateral in 58 cases and unilateral in 71 cases. The average age of the patients was 38.8 and gravidity 1.8, with 43.1% of them being infertilite. In 12.2, 45.4 and 84.6% of them, irregular menstruation, hypermenorrhea, and dysmenorrhea were recorded, respectively. Regarding complicated lesions, 49 patients had fibroid, 33 uterine adenomyosis, and 13 rectocervical endometriosis. Of the 129 cases, 61.3% were regarded as of the cystic type, 30.2% as of the non-cystic type, and 8.5% as of the cystic/non-cystic type. The average ages were 35.5 and 41.6 years for cystic and non-cystic types, respectively. The incidence of each type of complicated lesion mentioned above was greater in the non-cystic type than that in the cystic type. The pathogenetic investigation suggested that cystic endometriosis in the ovary might mainly be ascribed to the endometrioid metaplasia of the celomic epithelium and that non-cystic endometriosis might occasionally originate from metastasis or implantation of endometrial tissues. In addition to this, the lesions which were histologically diagnosed as endometriosis might sometimes include obsolete follicle cysts undergoing luteinization.