Evaluation and management of endometriosis.

The initial diagnostic investigations for endometriosis are physical examination and pelvic ultrasound. The pelvic examination should include a speculum examination and vaginal palpation. Mobility, fixation and/or tenderness of the uterus and site-specific tenderness in the pelvis should be evaluated. Transvaginal ultrasound and pelvic magnetic resonance imaging are recommended to evaluate the extent of the endometriosis and to determine whether any urinary tract or bowel procedures might also be required during surgical resection. Quality of life should be assessed by using the Endometriosis Health Profile-30, its short version EHP-5 or the generic quality of life questionnaire SF-36. Management of endometriosis is recommended when it has a functional impact (pain, infertility) or causes organ dysfunction. Many gynecological societies have published different guidelines for the evaluation and management of endometriosis. However, the complexity of this disease together with the different available treatments lead to significant discrepancies between the recommendations. Postmenopausal endometriosis should be considered when a patient has a history of symptoms before menopause including dysmenorrhea, dyspareunia, dyschezia, infertility and chronic pelvic pain. Malignant transformation of endometriosis is estimated to occur in about 0.7-1.6% of women affected by endometriosis. Endometriosis is associated with an increased risk of ovarian cancer, specifically clear cell, endometrioid and low-grade serous types.

Postmenopausal hyperandrogenism.

Postmenopausal hyperandrogenism is a state of relative or absolute androgen excess originating from the adrenal glands and/or ovaries clinically manifested by the presence of terminal hair in androgen-dependent areas of the body, and other manifestations of hyperandrogenism such as acne and alopecia or the development of virilization. In such circumstances, physicians must exclude the possibility of rare but serious androgen-producing tumors of the adrenal glands or ovaries. Worsening of undiagnosed hyperandrogenic disorders such as polycystic ovary syndrome, congenital adrenal hyperplasia, ovarian hyperthecosis, Cushing syndrome and iatrogenic hyperandrogenism should be considered for differential diagnosis. Elevated serum testosterone not only causes virilizing effects, but also will lead to hypercholesterolemia, insulin resistance, hypertension and cardiac disease. An ovarian androgen-secreting tumor, which is diagnosed in 1-3 of 1000 patients presenting with hirsutism, comprises less than 0.5% of all ovarian tumors. Adrenal tumors, including non-malignant adenomas and malignant carcinomas, are less common than ovarian tumors but cause postmenopausal virilization. Measurement of serum testosterone, sex hormone-binding globulin, dehydroepiandrosterone sulfate, androstenedione and inhibin B is necessary in postmenopausal women with the complaints and signs of hyperandrogenism. Some tests to discard Cushing syndrome should also be done. After an etiological source of androgen hypersecretion has been suspected, we recommend performing magnetic resonance imaging of the adrenal glands or ovaries. Medical management with gonadotropin-releasing hormone agonist/analogues or antagonists has been reported for women who are either unfit for surgery or in whom the source of elevated testosterone is unidentified.

Sexual function through decades: association with androgens and cardiometabolic features.

Aim: This study aimed to determine the change in sexual function among Turkish women through decades and to define the association between sexual dysfunction and androgens and cardiometabolic features.Materials and methods: A total of 206 postmenopausal women aged 50-69 years and 210 premenopausal women aged 30-49 years who applied to menopause and gynecology clinics at a university-affiliated education and research hospital were included in this prospective study. Groups were constructed according to decades (i.e., 30-39, 40-49, 50-59, and 60-69 years). Sexual function was assessed between the groups, using the Female Sexual Function Index (FSFI). Cardiometabolic features and androgen levels were also compared between the groups.Results: Sexual function determined at each decade by FSFI scores were 27.18, 23.11, 18.40, and 11.35, respectively (fourth, fifth, sixth, and seventh decade). Desire, arousal, and satisfaction domains tended to be lower in the 40s than in the 30s. As time passes after the 30s, the total FSFI score decreased until the late 60s. Serum total testosterone, androstenedione, and dehydroepiandrostenedione sulfate (DHEAS) levels decreased through the decades. There was no correlation between cardiometabolic features, androgens, and FSFI scores.Conclusion: According to our survey, sexual function decreases starting at the age of 30 and continues to drop until the late 60s among postmenopausal women. There was no association between sexual dysfunction and androgen levels in premenopausal women. The serum DHEAS level was associated with sexual dysfunction only among postmenopausal women. There was no association between sexual dysfunction and cardiometabolic features in either premenopausal or postmenopausal women.

Assessment and management of B3 breast lesions with atypia: a focused review.

Breast lesions with atypia are a spectra of diseases that confer increased risk of breast cancer because of an increased probability of finding concomitant cancer after excision, or evolution toward in situ or invasive cancer over the long term. The widespread use of radiologic tools and core needle breast biopsies, in recent years, has led to an increase in the diagnosis of these atypical breast lesions. Concurrent with this has been an improvement in the classification and pathogenesis of these lesions. Current evidence suggests that the recognition and treatment of patients with atypical histology after biopsy and surgical excision requires a multidisciplinary approach to decrease the overdiagnosis and overtreatment risks. This focused review investigates the controversy and current management of atypical ductal hyperplasia, lobular neoplasia, flat epithelial atypia, and intraductal papilloma with atypia along with the risk-reducing strategies.

The association between sexual dysfunction and metabolic syndrome among Turkish postmenopausal women.

Objective: The aim of this study is to determine the association between sexual dysfunction and metabolic syndrome (MS) among Turkish postmenopausal women Methods: In total, 290 postmenopausal women between the ages of 50 and 70 years and 265 premenopausal women between the ages of 30 and 49 years who applied to Menopause and Gynecology Clinics at Marmara University-affiliated Pendik Education and Research Hospital, Istanbul, Turkey were included in this prospective survey. Sexual function was assessed using the Female Sexual Function Index (FSFI). A FSFI total score of <26.5 was suggestive of sexual dysfunction. MS was assessed by the National Cholesterol Education Program Adult Treatment Panel III criteria. Results: Sexual dysfunction prevalence among postmenopausal women was 64.6% in relation to 42.1% in premenopausal women (p = 0.001). MS prevalence was 13.5% among premenopausal women and 15.5% among postmenopausal women (p = 0.57). The total FSFI score and each score in the desire, arousal, lubrication, orgasm, satisfaction, and dyspareunia domains of the FSFI did not differ between premenopausal and postmenopausal women, regarding the MS status. In the premenopausal group, 45.7% of women without MS and 37% of women with MS had lower sexual dysfunction (p = 0.40); whereas in the postmenopausal group, 62.2% of women without MS and 77.4% of women with MS had lower sexual function (p = 0.22). Conclusion: In our study population, the rate of sexual dysfunction increased in postmenopausal women in contrast to premenopausal women. The MS status did not make a difference in terms of sexual dysfunction either in premenopausal or postmenopausal women. Since our survey was conducted in a tertiary medical center which gave medical care service to women from middle and low socioeconomic classes, our results should be confirmed by a large multicenter survey enrolling women from all different socioeconomic classes.

Surgical challenges in the treatment of perimenopausal and postmenopausal endometriosis.

Endometriosis is classically defined as a chronic, recurrent and progressive disease. It is known to be estrogen-dependent, but can still be observed during the peri- and postmenopausal periods. Medical management of endometriosis is palliative symptomatic relief. Surgery when properly and timely performed for the right person may treat endometriosis. However, there is always a risk of possible major or minor surgical complications, as well as loss of some functions due to nerve damage. Management of endometriosis in the woman approaching the end of her reproductive life may require special attention both due to the potential for recurrence and transformation into various endometriosis-associated malignancies.

Thyroid disease in the perimenopause and postmenopause period.

The interpretation of thyroid function tests should be cautiously made during the perimenopause and postmenopause period bearing in mind that physiologic changes do exist in this group of women in terms of secretion and metabolism of thyrotropin and thyroid hormones. Moreover the incidence of thyroid disorders increases in postmenopausal and elderly women. There is no consensus for screening postmenopausal women even though there is well-known evidence about the effect of thyroid status on cognitive function, cardiovascular risk, bone turnover, and longevity. The diagnosis of any thyroid disorder is challenging in these patients because the symptoms are more subtle and attributed to menopausal symptoms. Management requires more attention in this population than that of younger groups, because high doses of L-thyroxine can lead to cardiac complications and increased bone turnover. Furthermore radio-iodine is preferred in treatment of hyperthyroidism in older patients. The risk of nodular thyroid disease and thyroid cancers increases in this group. Although the diagnostic approach is the same as for young patients, the risk of surgery is high and disease prognosis is worse. Women with any form of thyroid disease should be treated according to the current guidelines. Decision for menopausal hormonal therapy should be individualized regardless of the concomitant presence of thyroid disorders.

Native tissue repair versus mesh repair in pelvic organ prolapse surgery.

In pelvic organ prolapse, the anatomical defects develop at the anterior (anterior vaginal wall), the posterior (posterior vaginal wall) and the apical (the uterus/cervix or the apex of the vagina, vaginal vault or cuff scar after hysterectomy) compartments. These defects occur in more than one compartment. Treatment of pelvic organ prolapse is commonly surgical, aiming to restore the anatomy of structures supporting the pelvic organs. The surgical repair techniques are classified as 'native tissue repair (NTR)' when only pelvic organ support tissues are used and 'augmented repair (AR)' when some other material (prosthesis or graft) is used to reinforce the defective support system. In this review, issues related to the basic science of meshes, and NTR versus mesh or graft AR procedures for pelvic organ prolapse are discussed while considering the varying risks and benefits according to the prolapsed compartment.

Fertility in midlife women.

Reduced maternal fertility is the consequence of depletion of follicles with maternal aging. In a 35-year-old woman, approximately 9.1% of the residual follicle pool disappears annually without entering into the growing stage, whereas, in a 45-year-old woman, this number triples. After the age of 35 years, the frequency of aneuploidies in oocytes increases sharply. Roughly 50-70% of mature oocytes from a 40-year-old woman have chromosomal abnormalities. The clinical pregnancy and implantation rates are lower in midlife women. Various controlled ovarian stimulation interventions have been suggested for the management of women in advanced age, most of whom are likely to be poor-responder patients. Currently, systematic reviews and meta-analyses suggest that there is insufficient evidence to recommend most of the treatments proposed to improve pregnancy rates in these poor responders. Minimal stimulation or natural cycle in vitro fertilization may be offered, without compromising the already existing pregnancy results.

Association of serum paraoxonase concentration with serum lipid levels and bone mineral density measurements in early postmenopausal women.

OBJECTIVE: To determine the association of serum paraoxonase concentration with serum lipid levels and bone mineral density in early postmenopausal Turkish women. DESIGN: One hundred healthy postmenopausal women were included in a cross-sectional study in a University hospital clinic. Blood was drawn from women who had bone mineral density (BMD) measurements during routine visits. BMD of the lumbar vertebrae was measured by dual-energy X-ray absorptiometry. The serum paraoxonase concentration and serum lipid levels were measured. Women were divided into two groups: those with normal lumbar vertebrae BMD and those with osteopenic lumbar vertebrae. Serum paraoxonase concentration was compared between the groups. The correlation between serum paraoxonase concentration and bone mass parameters was performed using Pearson's test. RESULTS: The paraoxonase concentration in the osteopenic group was significantly lower than in the group with normal lumbar vertebrae BMD. The paraoxonase concentration was moderately correlated with total cholesterol, low density lipoprotein cholesterol and triglyceride levels among early postmenopausal Turkish women. CONCLUSIONS: Early postmenopausal women with osteopenic lumbar vertebrae have significantly lower paraoxonase concentration than those with normal lumbar vertebrae BMD. Further studies are needed to clarify the associations between the osteoporosis risk factors and paraoxonase concentration during late postmenopausal years.

The association of osteopenia with levels of serum 25-hydroxyvitamin D and HOMA-IR values.

OBJECTIVE: To determine the association of osteopenia with levels of serum 25-hydroxyvitamin D and HOMA-IR values in postmenopausal women. Methods One hundred healthy postmenopausal women were included in a cross-sectional study. Venous blood was collected after an overnight fast and 25-hydroxyvitamin D, glucose and insulin levels were measured. HOMA-IR was calculated. Bone mineral density was measured with a dual X-ray absorptiometer. RESULTS: There was no difference in serum 25-hydroxyvitamin D levels and HOMA-IR values between the two groups. A weak positive correlation between serum 25-hydroxyvitamin D levels and osteopenia was detected. Insulin resistance had a weak negative association with osteopenia. CONCLUSIONS: The correlations between osteopenia and serum 25-hydroxyvitamin D levels and HOMA-IR values were weak among early postmenopausal women.

Estrogen receptor gene polymorphisms in a group of postmenopausal Turkish women: association with bone mineral density.

OBJECTIVE: To evaluate the frequency of the estrogen receptor (ER) gene PvuII and XbaI polymorphisms and their associations with bone mineral density (BMD) in a group of postmenopausal Turkish women. DESIGN: A total of 125 healthy postmenopausal women and 125 premenopausal healthy young women as controls were included in the study. The PvuII and XbaI polymorphisms in the ER gene were studied by the polymerase chain reaction-restriction fragment length polymorphism method. The BMD of the lumbar vertebrae and femoral neck were measured by dual-energy X-ray absorptiometry. RESULTS: The frequencies of the ERα PVuII genotypes PP, Pp and pp were 20%, 54.4% and 25.6% in premenopausal and 24.8%, 44.8% and 30.4% in postmenopausal women, respectively. The frequencies of the ER XbaI genotypes XX, Xx, xx were 16.8%, 48.8% and 34.4% in premenopausal and 16.8%, 48% and 35.2% in postmenopausal women, respectively. There was no difference in the frequencies of ER gene polymorphisms between premenopausal and postmenopausal women. BMD measurements were not different between ER PvuII and XbaI genotypes in premenopausal and postmenopausal women. CONCLUSIONS: ER gene PvuII and XbaI polymorphisms have no major influence on bone mineral density in our group of postmenopausal women.

Should we consider assessment of bone mineral density earlier in postmenopausal women with pelvic organ prolapse?

OBJECTIVE: To investigate a possible association between the presence of pelvic organ prolapse and osteopenia or osteoporosis in early postmenopausal women. DESIGN: Eighty-seven postmenopausal women between the ages of 55 and 60 years who had been admitted to the Gynecology or Menopause Outpatient clinics of Marmara University, School of Medicine were included in the study. Quantification of pelvic organ prolapse was performed for each patient. The bone mineral density measurements of the lumbar vertebrae by dual-energy X-ray absorptiometry were compared between the groups with and without pelvic organ prolapse. RESULTS: The mean T-scores for the lumbar area for women with or without pelvic organ prolapse were comparable between the study groups. CONCLUSIONS: It appears that presence of pelvic organ prolapse in early postmenopausal women is not helpful in predicting osteoporosis.

Vitamin D receptor gene polymorphisms in a group of postmenopausal Turkish women: association with bone mineral density.

OBJECTIVE: To determine the frequency of the vitamin D receptor (VDR) gene polymorphisms BsmI, ApaI, TaqI and FokI and their associations with bone mineral density (BMD) in postmenopausal Turkish women. DESIGN: One hundred and thirty healthy postmenopausal women and 130 premenopausal healthy women acting as controls were included in the study. The BsmI, FokI, ApaI and TaqI polymorphisms in the VDR gene were studied by polymerase chain reaction-restriction fragment length polymorphism method. The BMD of the lumbar vertebrae and femur neck were measured by dual-energy X-ray absorptiometry. Comparisons between the groups were performed using the paired t-test and ANOVA. χ (2) or contingency tables were used to analyze qualitative results. RESULTS: Genotypes BB, Bb and bb occurred in premenopausal women with frequencies of 16.92%, 50% and 33.08% and in postmenopausal women with frequencies of 16.92%, 56.15% and 26.92%, respectively. Genotypes FF, Ff, ff occurred in premenopausal women with frequencies of 47.69%, 42.31% and 10% and in postmenopausal women with frequencies of 50.77%, 42.31% and 6.92%, respectively. Genotypes AA, Aa, aa occurred in premenopausal women with frequencies of 23.85%, 56.15% and 20% and in postmenopausal women with frequencies of 26.15%, 46.15% and 27.70%, respectively. Genotypes TT, Tt and tt occurred in premenopausal women with frequencies of 37.69%, 45.38% and 16.92% and in postmenopausal women with frequencies of 39.23%, 45% and 15.38%, respectively. There was no difference in the frequencies of VDR gene polymorphisms between premenopausal and postmenopausal women. BMD measurements were not different between genotypes in premenopausal and postmenopausal women. CONCLUSIONS: The VDR gene BsmI, FokI, ApaI and TaqI polymorphisms have no major influence on bone mineral density in our group of postmenopausal women.

The impact of tibolone and hormone therapy on serum C-reactive protein, tumor necrosis factor-alpha and hepatocyte growth factor in postmenopausal women.

OBJECTIVE: To investigate the effect of tibolone and hormone treatment on serum C-reactive protein, tumor necrosis factor-alpha and hepatocyte growth factor as independent markers of cardiovascular disease. DESIGN: Ninety-five normotensive and healthy postmenopausal women with no systemic or cardiac disease who attended the Marmara University Menopause Outpatient Clinic were included in this study. The women were assigned into three groups. The women who accepted hormone replacement therapy were randomized to two groups. Group 1 received 0.625 mg conjugated estrogen (CE) +2.5 mg medroxyprogesterone acetate (MPA)/day. Group 2 received 2.5 mg tibolone/day. Group 3 was the control group consisting of women who did not want hormone replacement therapy. Serum samples were measured for highly specific C-reactive protein, tumor necrosis factor and hepatocyte growth factor before the treatment and after 6 months of therapy. Values at the end of the 6th month and baseline were compared. RESULTS: The increase in C-reactive protein and the decrease in tumor necrosis factor-alpha levels demonstrated at the end of treatment were statistically significant, in both the hormone therapy and tibolone groups. However, the decrease in hepatocyte growth factor was significant only in the tibolone group. CONCLUSIONS: The positive impact of both tibolone and hormone therapy on inflammatory markers appears to be protective against cardiovascular diseases. However, the clinical implications of these findings are yet to be evaluated in large clinical trials.

Obstetric outcomes of recurrent pregnancy loss patients diagnosed with inherited thrombophilia.

BACKGROUND: Recurrent pregnancy loss (RPL) is defined by two or more failed pregnancies. The relation between RPL and inherited thrombophilia requires anticoagulant therapy during pregnancy. However the obstetric outcomes have not been well defined in these RPL patients diagnosed with inherited thrombophilia, who have been given anticoagulant therapy. AIM: To investigate the obstetric outcomes in pregnant women with RPL who are given low molecular weight heparin (LMWH) and low-dose aspirin due to diagnosis of inherited thrombophilia. METHODS: A hundred and eight RPL women were diagnosed with inherited thrombophilia, and 98 women were diagnosed with unexplained RPL. The patients with inherited thrombophilia were given LMWH and low-dose aspirin. Unexplained RPL patients were not given any medicine. The obstetric outcomes of participants were noted. RESULTS: In thrombophilic group, the live-birth levels were significantly higher [90 (83%) vs 67 (68%) p < 0.05], and the miscarriage levels were significantly lower than that in the control group [14 (13%) vs 27 (28%) p < 0.01]. The number of patients with preeclampsia was significantly higher in the thrombophilic group [16 (15%) vs 6 (6%) p < 0.05]. The number of preterm births was significantly higher than that of the controls [25 (23%) vs 10 (10%) p < 0.05]. The median gestation age of delivery was 35 weeks for thrombophilic patients and 38 weeks for controls (p < 0.05). CONCLUSION: The RPL patients diagnosed with inherited thrombophilia and who were given LMWH with low-dose aspirin had higher live-birth rates and lower miscarriage rates than those in the unexplained RPL patients. Increased risk of preeclampsia is seen in RPL patients with inherited thrombophilia despite thrombophilia prophylaxis.