Insomnia in Postmenopausal Women: How to Approach and Treat It?

Insomnia is one of the major complaints of menopausal women with advancing age and may be complexly related to a variety of causes. However, there is still a lack of standards on the general approach and treatment for insomnia in menopausal women. The aim of this review is to summarize recent pathogenic theories of sleep disturbance in the menopausal period and discuss the approach and management of insomnia in postmenopausal women. Sleep disturbances in menopausal women may be associated with physical and psychiatric factors and other comorbid diseases. Careful history taking and multidisciplinary physical and psychosocial evaluation are necessary and, in particular, comorbidities related to sleep disorders, such as obstructive sleep apnea, must be taken into consideration. A unique aspect of insomnia in postmenopausal women is that menopausal symptoms due to hormonal decline can be closely related to sleep disturbances. Therefore, menopausal hormone therapy (MHT) should be considered as the treatment of choice among pharmacological treatments following cognitive behavioral therapy, which is suggested as the first-line treatment in the general population insomnia treatment guidelines. Additionally, melatonin and 5HT-based drugs, which have fewer side effects, along with MHT should be preferentially recommended in menopausal women.

The Associations of Vitamin D with Ovarian Reserve Markers and Depression: A Narrative Literature Review.

Since the identification of vitamin D receptors in both the female reproductive tract and the central nervous system, further data have shown that vitamin D is involved in the processes of reproductive and mental health. This paper reviews current research on the associations of vitamin D with ovarian reserve markers and depression and discusses the potential role of vitamin D in their relationships. There have been numerous studies reporting that vitamin D was significantly related to ovarian reserve markers and depression in basic or clinical research, but some observational and interventional clinical studies have shown inconsistent results. Nevertheless, recent meta-analyses of interventional studies have provided promising results showing that vitamin D supplementation significantly improves ovarian reserve metrics, especially in a subgroup of women with normal or diminished ovarian reserve, and decreases depressive symptoms and risk. The demonstration of an association of vitamin D with both ovarian reserve and depression could suggest that vitamin D may be another important key in explaining female reproductive depression. Larger-scale studies in standardized settings will be needed in order to gain further insight into the role of vitamin D in female reproduction and depression.

Correlation between Serum 25-Hydroxyvitamin D Level and Depression among Korean Women with Secondary Amenorrhea: A Cross-Sectional Observational Study.

Vitamin D deficiency is considered a major public health problem worldwide and has been reported as having an association with depression. However, studies on the association between vitamin D deficiency and depressive symptoms in secondary amenorrhea (SA) patients are still scarce. This study examined the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and depressive symptoms among Korean women with SA. In this cross-sectional observational study, 78 patients with SA were initially recruited. Clinical and biochemical parameters, including serum 25(OH)D level, were measured. Data from 63 SA patients who met the study inclusion criteria and completed psychiatric assessments were finally analyzed. We analyzed their association with depression using a hierarchical regression model. The average serum 25(OH)D level was 34.40 ± 24.02 ng/mL, and 41.3% of the women with SA were vitamin D-deficient (<20 ng/mL). The total score of the Korean version of the Hamilton Depression Rating Scale (K-HDRS) was negatively related to serum 25(OH)D levels, free testosterone, and serum anti-Müllerian hormone (AMH) after adjusting for age and BMI (r = −0.450, p < 0.001; r = −0.258, p = 0.045; and r = −0.339, p = 0.006, respectively). Serum 25(OH)D levels and AMH levels were the most powerful predictors of depressive severity when using the K-HDRS in SA patients (ß = −0.39, p < 0.005; ß = −0.42, p < 0.005, respectively). This study showed that low serum 25(OH)D levels were associated with the severity of depressive symptoms in SA patients. This observation suggests that the evaluation of vitamin D deficiency for the risk of depression may be necessary in patients with SA.

Immunoregulatory protein V-set and immunoglobulin domain-containing 4 is overexpressed in patients with endometriosis.

AIM: V-set and immunoglobulin domain-containing 4 (VSIG4) is a potent negative regulator of T-cell responses and is suggested to regulate antitumor immunity. This study investigates whether VSIG4 is significantly expressed in endometriosis patients and the association between VSIG4 levels and serum cancer antigen (CA)-125 levels, VSIG4 levels and endometriosis severity. METHODS: Tumor tissues and peripheral blood samples were obtained during surgery from 42 endometriotic cyst and 21 nonendometriotic tumor patients. The levels of VSIG4 mRNA, VSIG4 protein expression in tumor tissue and serum soluble VSIG4 concentration were compared between the two groups. After dividing the cohort using the optimized cut-off values obtained by receiver operating characteristic curve analysis, we examined the association between VSIG4 levels and serum CA-125 levels, VSIG4 levels and the factors indicating endometriosis severity. RESULTS: The expressions of VSIG4 mRNA, VSIG4 protein and serum VSIG4 concentration were significantly increased in the endometriotic cyst group compared with the control group (P = 0.001, 0.002 and 0.049, respectively). The optimized VSIG4 cut-off values for endometriosis prediction were 0.71, 0.32 and 144.37 pg/mL, respectively. After cohort division using these values, high VSIG4 levels group showed significantly elevated CA-125 compared with low VSIG4 level group (P = 0.010, 0.043 and 0.039, respectively). There was no association between VSIG4 levels and the factors indicating endometriosis severity. CONCLUSION: The expression of VSIG4 in endometriosis patients is increased compared with nonendometriotic tumor patients, and higher VSIG4 levels are significantly associated with higher serum CA-125 levels. VSIG4 may be importantly involved in the immunological alteration of endometriosis.

Serum vitamin D levels and ovarian reserve markers in secondary amenorrhea patients: Is there a link?

OBJECTIVE: To investigate whether serum 25-hydroxyvitamin D [25(OH)D] level is associated with ovarian reserve markers in secondary amenorrhea (SA) patients. METHODS: Sixty-three women diagnosed with SA were recruited during 12 months from the initiation of this prospective observational study. Serum 25(OH)D levels, serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC) were estimated in study participants and ovarian reserve markers were compared between participants with vitamin D deficiency and those with normal vitamin D levels. RESULTS: Of the 63 participants, 27 (42.9%) were vitamin D deficient (<20 ng/mL) and 36 (57.1%) had normal vitamin D levels. The mean AMH levels and AFC were 10.86±8.94 µ/L and 15.23±7.65 in the vitamin D deficient group, and 7.24±5.62 µ/L and 12.30±6.95 in the normal vitamin D group. Univariate and multivariate linear regression analysis of log10 transformed AMH and AFC with serum 25(OH)D adjusted for age and body mass index confirmed no association between vitamin D levels and AMH levels or AFC. There was also no correlation between serum 25(OH)D and AMH levels or AFC in all participants. However, participants with vitamin D deficiency had an increased chance of having polycystic ovarian syndrome (PCOS) as cause of SA than those with normal vitamin D levels (adjusted odds ratio, 7.559; 95% confidence interval, 1.28-44.65; P=0.026) after adjustment for clinical factors by logistic regression model. CONCLUSION: There was no correlation between serum 25(OH)D levels and ovarian reserve markers in SA patients, but vitamin D deficiency may be linked to PCOS patients.

Pulmonary embolism in a healthy woman using the oral contraceptives containing desogestrel.

Venous thromboembolism is well known as one of the rare but serious adverse effects of combined oral contraceptives (COCs). The COCs with third and fourth generation progestogens were found to have higher risk of venous thrombosis than those with second generation progestogens. We present a case of pulmonary embolism in a 23-year-old nulligravid woman who was using COCs containing the third generation progestogen (desogestrel). At the time of presentation of the adverse effect, she had been using the COCs for 4 months. She had no additional risk factors for thrombosis such as smoking, surgery, tumor as well as genetic factors. This case demonstrates even young women in otherwise good health may be at risk of venous thromboembolism from low-dose formulations of COCs as an over-the-counter drug. We describe this case with a brief review of literatures.

Comparison of cervical lengths using transabdominal and transvaginal sonography in midpregnancy.

OBJECTIVES: Cervical length assessment is helpful to predict and prevent preterm birth. However, transvaginal sonography is not easy to perform. The aim of this study was to investigate the relationship and discrepancies between cervical lengths measured by transabdominal and transvaginal sonography in midpregnancy. METHODS: Transabdominal and transvaginal cervical lengths were measured in 255 pregnant women between 20 and 29 gestational weeks. The discrepancies in cervical lengths between the two methods were analyzed for the following maternal and fetal conditions: (1) vertex versus breech fetal presentation, (2) whether the fetal presenting part overlay the cervical internal os, (3) whether both the internal os and external os were visible or only the internal os was clearly visible, (4) maternal bladder filling status, (5) maternal age, (6) parity, and (7) gestational age. RESULTS: The mean cervical lengths were not significantly different (mean ± SD, 3.88 ± 0.73 cm on transabdominal sonography and 3.93 ± 0.72 cm on transvaginal sonography; P = .129; Pearson r = 0.75). The 5th-percentile transabdominal cervical length was 26.0 mm, and the transvaginal length was 27.8 mm. There were significant discrepancies between the two methods in the cases in which a fetal presenting part overlay the internal os, in the cases in which the external os was not clearly visible, and in primiparous women. Transabdominal cervical measurements were consistently shorter than transvaginal measurements in the cases with discrepancies. CONCLUSIONS: Transabdominal cervical length measurements are correlated with transvaginal measurements overall, and the transabdominal length is consistently shorter than the transvaginal length in cases with discrepancies. Transabdominal sonography could be used as a cervical length screening tool.

Fertility preservation in female cancer patients.

With improved survival rates among cancer patients, fertility preservation is now being recognized as an issue of great importance. There are currently several methods of fertility preservation available in female cancer patients and the options and techniques via assisted reproduction and cryopreservation are increasing, but some are still experimental and continues to be evaluated. The established means of preserving fertility include embryo cryopreservation, gonadal shielding during radiation therapy, ovarian transposition, conservative gynecologic surgery such as radical trachelectomy, donor embryos/oocytes, gestational surrogacy, and adoption. The experimental methods include oocyte cryopreservation, ovarian cryopreservation and transplantation, in vitro maturation, and ovarian suppression. With advances in methods for the preservation of fertility, providing information about risk of infertility and possible options of fertility preservation to all young patients with cancer, and discussing future fertility with them should be also considered as one of the important parts of consultation at the time of cancer diagnosis.

Association between serum estradiol level and coronary artery calcification in postmenopausal women.

OBJECTIVE: The aim of this study was to estimate whether coronary artery calcification is associated with serum estradiol (E2) level in postmenopausal women. METHODS: We performed a multidetector CT scan of the heart and measured the coronary artery calcium score (CACS) in 436 postmenopausal women who did not take postmenopausal hormone therapy. Women were divided into two groups according to the CACS (≥100 or <100). Serum E2 level, lipid profile, bone mineral densities of the lumbar vertebrae and femoral neck, current statin treatment status, and other coronary risk factors were analyzed in these two groups. RESULTS: The proportion of women with a higher serum E2 level (> or =20 pg/mL) was significantly higher in the lower-CACS (<100) group compared with the higher-CACS ((> or =100) group (34.0% vs 12.5%; P < 0.05). The distribution of CACS was significantly different between women with higher and lower (<20 pg/mL) serum E2 levels (P < 0.05), and the CACS was significantly lower in the group with a higher serum E2 level (P = 0.002). After adjusting various risk factors by weighted logistic regression model using inverse probability of treatment weighting, women with a higher serum E2 level had a reduced chance of having a higher CACS (crude odds ratio, 0.28; 95% CI, 0.08-0.95; P = 0.04; adjusted odds ratio, 0.25; 95% CI, 0.07-0.86; P = 0.03). CONCLUSIONS: Postmenopausal women with a higher serum E2 level had a reduced CACS independent of age and other coronary risk factors. These retrospective analyses might suggest that a higher level of E2 possibly lowers the calcified-plaque burden of coronary arteries in postmenopausal women.

Effects of pioglitazone on ovarian stromal blood flow, ovarian stimulation, and in vitro fertilization outcome in patients with polycystic ovary syndrome.

OBJECTIVE: To investigate the effects of pioglitazone on ovarian stimulation, in vitro fertilization (IVF) outcome, and intraovarian stromal blood flow in patients with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized, controlled trial. SETTING: University-affiliated infertility clinic. PATIENT(S): Sixty infertile patients with PCOS resistant to clomiphene citrate. INTERVENTION(S): An IVF protocol involving use of a gonadotropin-releasing hormone (GnRH) antagonist and oral contraceptive pretreatment. Patients were randomized into two groups: pioglitazone (30 mg daily) in the study group or placebo in the control group, commenced on the day on which oral contraceptive intake began. MAIN OUTCOME MEASURE(S): Ovarian stimulation, IVF outcome, and resistance index of the intraovarian stromal artery. RESULT(S): The resistance index value on the day of human chorionic gonadotropin (hCG) injection in the study group was statistically significantly higher in the study group than in controls. The serum estradiol level and number of retrieved oocytes were statistically significantly lower in women treated with pioglitazone. However, the number of mature oocytes and fertilized oocytes, and the clinical pregnancy rate were similar in both groups. CONCLUSION(S): Pioglitazone therapy reduced intraovarian stromal blood flow and might be beneficial in improving both the response to ovarian stimulation and IVF outcome in PCOS patients.

Etiologic characterization of recurrent miscarriages in Koreans.

OBJECTIVE: To investigate recurrent miscarriages in Koreans in terms of causative factors and the prognosis for subsequent successful pregnancies in primary and secondary recurrent miscarriages cases. STUDY DESIGN: The study retrospectively examined the clinical records of 222 recurrent miscarriage cases that were presented at the Department of Obstetrics and Gynecology, Asan Medical Center, Seoul, Korea, from July 1989 to June 2008. The cases were classified according to the cause and pregnancy rates after the primary and secondary abortions were compared using the chi2 test. RESULTS: The etiologic analysis indicated that anatomic abnormality (29.4%) was the most common cause of recurrent miscarriage in Koreans, followed by immunologic (26.7%), inexplicable (24.1%), endocrinologic (15.0%) and genetic (11.2%) causes. The subsequent successful pregnancy rate was higher in the secondary recurrent miscarriage group than the primary recurrent miscarriage group (47.9% vs. 31.7%, p < 0.05). CONCLUSION: The causative factors of recurrent miscarriages in Koreans differed from those reported in Western studies on the frequency of causes. The prognosis for subsequent successful pregnancies was better in the secondary recurrent miscarriage group, as we expected.

Comparison of GnRH antagonist protocol with or without oral contraceptive pill pretreatment and GnRH agonist low-dose long protocol in low responders undergoing IVF/intracytoplasmic sperm injection.

This prospective randomized study was performed to compare the efficacy of GnRH antagonist multiple-dose protocol (MDP) with or without oral contraceptive pill (OCP) pretreatment and GnRH agonist low-dose long protocol (LP) in 82 patients undergoing IVF/intracytoplasmic sperm injection (ICSI). GnRH antagonist MDP with OCP pretreatment was at least as effective as GnRH agonist low-dose LP in low responders, and can benefit the low responders by reducing the amount of FSH and the number of days of stimulation required for follicular maturation.