Clinical evaluation of high-intensity focused ultrasound ablation combined with mifepristone and levonorgestrel-releasing intrauterine system to treat symptomatic adenomyosis.

OBJECTIVE: To evaluate the clinical efficacy of the combination of high-intensity focused ultrasound (HIFU), mifepristone, and levonorgestrel-releasing intrauterine system (LNG-IUS) in adenomyosis treatment. METHODS: HIFU treatment was performed in 123 patients with symptomatic adenomyosis who had refused treatment with gonadotropin-releasing hormone agonist (GnRH-a) at Anyang Maternal and Child Health Care Hospital. In the control group, 34 patients were treated with HIFU alone, 29 patients with HIFU combined with mifepristone, 10 patients with HIFU combined with LNG-IUS. In the study group, 50 patients were treated with HIFU combined with mifepristone and LNG-IUS. RESULTS: Uterine volume, dysmenorrhea pain score, menstruation volume score, and serum CA125 level were significantly lower after treatment with HIFU combined with mifepristone and LNG-IUS than before treatment (p < .05). Moreover, hemoglobin level was significantly higher than that before treatment (p < .05). After 24 months, the efficacy of HIFU combined with mifepristone and LNG-IUS was significantly higher than that of HIFU alone, HIFU combined with mifepristone or HIFU with LNG-IUS (p < .05). CONCLUSIONS: Combination therapy of HIFU, mifepristone, and LNG-IUS is an effective, safe, and inexpensive treatment for patients with symptomatic adenomyosis. This combination therapy demonstrates superior efficacy to treatment with HIFU alone, HIFU combined with mifepristone, and HIFU combined with LNG-IUS.

Paeonol alleviates primary dysmenorrhea in mice via activating CB2R in the uterus.

BACKGROUND AND PURPOSE: Primary dysmenorrhea is the most common gynaecologic problem in menstruating women and is characterized by spasmodic uterine contraction and pain symptoms associated with inflammatory disturbances. Paeonol is an active phytochemical component that has shown anti-inflammatory and analgesic effects in several animal models. The aim of this study was to explore whether paeonol is effective against dysmenorrhea and to investigate the potential mechanism of cannabinoid receptor signalling. EXPERIMENTAL APPROACH: Dysmenorrhea was established by injecting oestradiol benzoate into female mice. The effects of paeonol on writhing time and latency, uterine pathology and inflammatory mediators were explored. Isolated uterine smooth muscle was used to evaluate the direct effect of paeonol on uterine contraction. KEY RESULTS: The oral administration of paeonol reduced dysmenorrhea pain and PGE2 and TNF-α expression in the uterine tissues of mice, and paeonol was found to be distributed in lesions of the uterus. Paeonol almost completely inhibited oxytocin-, high potassium- and Ca2+-induced contractions in isolated uteri. Antagonists of CB2R (AM630) and the MAPK pathway (U0126), but not of CB1R (AM251), reversed the inhibitory effect of paeonol on uterine contraction. Paeonol significantly blocked L-type Ca2+ channels and calcium influx in uterine smooth muscle cells via CB2R. Molecular docking results showed that paeonol fits well with the binding site of CB2R. CONCLUSIONS AND IMPLICATIONS: Paeonol partially acts through CB2R to restrain calcium influx and uterine contraction to alleviate dysmenorrhea in mice. These results suggest that paeonol has therapeutic potential for the treatment of dysmenorrhea.

Soy-based infant formula feeding and menstrual pain in a cohort of women aged 23-35 years.

STUDY QUESTION: Is soy formula feeding during infancy associated with menstrual pain in reproductive-age women? SUMMARY ANSWER: Our data suggest that soy formula feeding during infancy is associated with several indicators of severe menstrual pain in reproductive-age women. WHAT IS KNOWN ALREADY: A prior study observed greater severity of menstrual pain in young women who as infants participated in feeding studies and were assigned to soy-based formula feeding. STUDY DESIGN, SIZE, DURATION: We used data from the Study of Environment, Lifestyle & Fibroids (SELF), a cohort of 1696 African-American women ages 23-35 years at enrollment. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Data on infant soy formula feeding was ascertained by self-administered questionnaire for 1553 participants, with 89% of participants receiving assistance from their mothers. Information on menstrual pain indicators was collected by web- and telephone-interview. We estimated the relative risk (RR) and 95% confidence interval (CI) using log-binomial regression, or log-multinomial regression, adjusting for participant age and maternal education. MAIN RESULTS AND THE ROLE OF CHANCE: Women ever fed soy formula as infants were more likely than unexposed women to report ever use of hormonal contraception for menstrual pain (RR 1.4, CI: 1.1-1.9) and moderate/severe menstrual discomfort/pain with 'most periods', but not 'every period', during early adulthood (ages 18-22 when not using hormonal contraception) (RR 1.5, CI: 1.1-2.0). LIMITATIONS, REASONS FOR CAUTION: We relied on retrospective recall to ascertain infant exposure to soy formula feeding and data on menstrual pain indicators. WIDER IMPLICATIONS OF THE FINDINGS: Our observations add to the growing body of literature from animal and human studies on the reproductive health consequences of early-life exposure to soy formula. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences and, in part, by funds allocated for health research by the American Recovery and Reinvestment Act. This research was also supported by grant K99NR017191 (KU). None of the authors has a conflict of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Mechanism of penehyclidine hydrochloride on a dysmenorrhea rat model.

Primary dysmenorrhea affects the quality of life in young women, particularly school and work performance. This study investigated the mechanisms of penehyclidine hydrochloride (PHC) efficacy on a rat model of primary dysmenorrhea. The model was induced by injecting both estradiol benzoate and oxytocin. Different doses of PHC were administrated intraperitoneally following estradiol benzoate administration. Writhing scores were assessed, and pathological changes of the uterus were observed via hematoxylin and eosin staining. Western blot and real-time PCR were used to evaluate the expression level of the M3 receptor, both TLR3 and TLR4 in uterine tissue, and the level of Ca2+ was measured in uterine tissues. Writhing scores significantly decreased in the PHC treatment group compared to model, and PHC alleviated the occurrence of edema or necrosis in the uteri compared to model group. PHC can decrease the M3 receptor, TLR3 , TLR4 expression, and the Ca2+ level compared to the model group. PHC is a potential candidate for the future treatment of primary dysmenorrhea due to its ability to attenuate muscarinic receptors and TLRs. Preclinical Research & Development.

Comparisons of pharmacokinetic and tissue distribution profile of four major bioactive components after oral administration of Xiang-Fu-Si-Wu Decoction effective fraction in normal and dysmenorrheal symptom rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiang-Fu-Si-Wu Decoction (XFSWD) has been widely used to treat primary dysmenorrhea in clinical practice for hundreds of years and shown great efficacy. One fraction of XFSWD, which was an elution product by macroporous adsorption resin from aqueous extract solution with 60% ethanol (XFSWE), showed great analgesic effect. The present study was conducted to investigate the possible pharmacokinetic and tissue distribution profiles of four major bioactive constituents (berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine) after oral administration of XFSWE in dysmenorrheal symptom rats, and to compare the difference between normal and dysmenorrheal symptom rats. MATERIALS AND METHODS: Estradiol benzoate and oxytocin were used to produce dysmenorrheal symptom rat model. The experimental period was seven days. At the final day of experimental period, both normal and dysmenorrheal symptom rats were orally administrated with XFSWE, and then the blood and tissues samples were collected at different time points. Berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine in blood and tissue samples were determined by LC-MS/MS. Pharmacokinetic parameters were calculated from the plasma concentration-time data using non-compartmental methods. The differences of pharmacokinetic parameters among groups were tested by one-way analysis of variance (ANOVA). RESULTS: There were statistically significant differences (P<0.05) in Cmax, Tmax, AUC(0-t), AUC(0-∞), MRT(0-t), MRT(0-∞) and CL/F between normal and dysmenorrheal symptom rats that orally administered with same dosage of XFSWE. In tissue distribution study, the results showed that the overall trend was C(Spleen)>C(Liver)>C(Kidney)>C(Uterus)>C(Heart)>C(Lung)>C(Ovary)>C(Brain)>C(Thymus), C(M-60 min)>C(M-120 min)>C(M-30 min)>C(C-60 min)>C(C-120 min)>C(C-30 min). The contents of protopine in liver, spleen and uterus were more than that in other tissues of dysmenorrheal symptom rats. Compared to normal rats, partial contents of the compounds in dysmenorrheal symptom rats׳ tissues at different time points had significant difference (P<0.05). CONCLUSIONS: This study was the first report about pharmacokinetic and tissue distribution investigation in dysmenorrheal symptom animals. The results indicated that berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine have higher uptake and slower elimination in the rats with dysmenorrheal syndrome, which suggests that the rate and extent of drug metabolism were altered in dysmenorrheal syndrome rats. And the results also demonstrated that berberine, protopine and tetrahydropalmatine in normal and dysmenorrheal symptom rats had obvious differences in some organs and time points, suggesting that the blood flow and perfusion rate of the organ were altered in dysmenorrheal symptom animals.

Plasma metabolic profiling of normal and dysmenorrhea syndrome rats and the effects of Xiang-Fu-Si-Wu Decoction intervention.

CONTEXT: Primary dysmenorrhea (PDM), a common, clinically heterogeneous endocrine disorder affecting young women, is associated with endocrinopathy and metabolic abnormalities. The Xiang-Fu-Si-Wu Decoction (XFSWD) is a traditional Chinese medicine preparation used to treat PDM. OBJECTIVE: In the current study, a plasma metabonomics method based on the ultra-high-performance liquid chromatography-quantitative time-of-flight-mass spectrometry (UHPLC-Q-TOF-MS) system was employed to examine the mechanism of XFSWD action in PDM. MATERIALS AND METHODS: Estradiol benzoate (0.01 g/kg/d) and oxytocin (5 mL/kg) were used to create the dysmenorrhea rat model. Based on the chromatographic data of plasma samples at different time-points following oral administration of XFSWD mixed in water (37.8 g crude herbs/kg) on day 7, partial least square (PLS) and discriminate analysis (DA) were applied to visualize group differentiation and marker selection. RESULTS: Systemic changes occurring in PDM reflect alterations in not only uterus function but also whole-body metabolism. The XFSWD was effective as a therapeutic agent for PDM by reflect metabolic pathway. Prostaglandins and lysophospholipids were identified as two marker types for oxytocin-induced dysmenorrhea syndrome, including LysoPC(18:4), LysoPE(22:2/0:0), LysoPC(17:0), PGJ2, 11-deoxy-11-methylene-PGD2, 15-deoxy-δ-12,14-PGJ2, LysoPC(20:3), etc. Specifically, the concentrations of prostaglandins compounds (PGJ2, 11-deoxy-11-methylene-PGD2, 15-deoxy-δ-12,14-PGJ2) were increased while those of lysophospholipid compounds [lysoPC(18:4), LysoPE(22:2/0:0), LysoPC(17:0)] were decreased to a significant extent (p < 0.05) in dysmenorrheal rats. Upon treatment with the XFSWD at 12 h, the concentrations of lysophospholipids showed no significant differences (P > 0.05) between the model and normal groups. The lysophospholipid levels were restored. Lysophospholipids were the key factors in phospholipid metabolism. Thus, disruption of phospholipids metabolism appears critical for the development of dysmenorrhea. The XFSWD exerted its effects by interfering with the sphingolipid metabolic pathway. DISCUSSION AND CONCLUSIONS: The metabonomics method presents a promising tool to treat PDM in animal models, and may be applicable for clinical treatment of the human disease in the future.

Decidual cast after discontinuation of oral contraceptives use in a young girl.

BACKGROUND: The differential diagnosis of tissue passed per vagina in a young girl includes aborted pregnancy, rhabdomyosarcoma, polyp, and very rarely decidual cast. CASE: A 10-year-old girl using oral contraceptives for menorrhagia presented with a decidual cast after discontinuing the drug. Symptoms disappeared during clinical follow-up without any intervention. CONCLUSIONS: Decidual cast formation is an unusual entity of unknown origin. It's generally seen during treatment with variable contraceptives. This is the first case described with desogestrel and it occurred after discontinuing treatment.

Serious menstrual bleeding associated with use of TNF alpha blocker: two cases.

Menstrual disorders associated with the use of TNF alpha blocker have been rarely reported. Herein, we reported two cases aged 31 and 41, presenting with excessive menstrual bleeding occured after adalimumab administration which was subsequently discontinued.

Membranous dysmenorrhea: a complication of treatment for endometriosis.

BACKGROUND: Progesterones are frequently used to treat endometriosis. Exaggerated response of the endometrium to high levels of progesterone can result in a decidualization reaction. Decidualization may cause an exacerbation of symptoms of dysmenorrhea associated with endometriosis. CASE: A 16-year-old girl with uterine didelphys and obstructed hemivagina presented with irregular bleeding and severe abdominal cramping after resection of the vaginal septum. Persistent endometriosis treated with norethindrone acetate resulted in severe colicky abdominal pain and expulsion of a decidual cast. CONCLUSION: Membranous dysmenorrhea can occur in response to excess progesterones. An understanding of the physiologic response of the endometrium to treatment will guide us to a high clinical suspicion of this rare entity when symptoms worsen in response to progesteronal treatment for endometriosis.

Chronic fatigue syndrome: a hormonal origin? A rare case of dysmenorrhea membranacea.

BACKGROUND: Membranous dysmenorrhea is a rare entity involving expulsion of fragments of endometrium retaining the shape of the uterus. The condition is often linked to high progesterone levels. An association with a chronic fatigue syndrome was never described. CASE: A 44-year-old woman with a chronic fatigue syndrome (CFS), presented with membranous dysmenorrhea after taking an oral contraceptive pill containing ethinylestradiol 0.02 mg and desogestrel 0.15 mg for 3 months in a continuous regimen as treatment for dysfunctional bleeding. Oral contraception was discontinued and she resumed normal menstruations. Remarkably, she mentioned complete disappearance of the CFS since expulsion of the tissue and started working again. CONCLUSION: The occurrence of membranous dysmenorrhea with a dissolving chronic fatigue syndrome is very rare and was never described before. This case suggests a hormonal dysfunction as a possible cause of chronic fatigue syndrome. A review of the literature on membranous dysmenorrhea is presented.

Menorrhagia and severe menstrual pain related to the use of adalimumab in a psoriatic.

The case is reported of a 32-year-old morbidly obese white woman who used adalimumab 40 mg every other week for 4 months for psoriatic arthritis, psoriasis vulgaris and inverse psoriasis with total clearance of her psoriasis who developed menorrhagia (at least twice the number of pads used daily for 4-6 days as opposed to 3-5 days previously) and severe menstrual pain. Treatment with Aviane (ethinyl estradiol and levonorgestrel) abated some of these menstrual symptoms. The symptoms resolved altogether when the adalimumab was discontinued. Menstrual disorders are listed as possible side effects from the use of infliximab and adalimumab in their respective package inserts and also for adalimumab and etanercept in the United Kingdom's Medicines and Healthcare products Regulatory Agency's drug side-effect database, but few case reports of menstrual side effects exist from including tumor necrosis alpha (TNFalpha) blockers. Physicians should be aware of the menstrual side effects of adalimumab and the role of oral contraceptive pills in treating such menstrual side effects.

Adverse effects of phytoestrogens on reproductive health: a report of three cases.

BACKGROUND: Phytoestrogens have been thought to have favorable effects on women's health and perhaps in offsetting cancers. The possible adverse effects of phytoestrogens have not been evaluated. CASES: Abnormal uterine bleeding with endometrial pathology in three women was found to be related to a high intake of soy products. The first woman had postmenopausal bleeding with uterine polyp, proliferative endometrium and a growing leiomyoma. The second woman presented with severe dysmenorrhea, abnormal uterine bleeding, endometriosis and uterine leiomyoma not responding to treatment. The third woman with severe dysmenorrhea, abnormal uterine bleeding, endometriosis and uterine leiomyomata presented with secondary infertility. All three women improved after withdrawal of soy from their diet. CONCLUSION: Additional information on phytoestrogens is necessary to ascertain their safety before they can be routinely used as supplements.

[Reproductive effects of occupational exposure to mercury on female workers in China: a meta-analysis].

OBJECTIVE: To analyze and evaluate the reproductive effects of occupational exposure to mercury among female workers and to identify relative sensitive indicators. METHODS: Documents on the relations of occupational exposure to mercury and reproductive effects on female workers were collected through computer and manually that were published in Chinese language during 1989-2006. After strict selection, homogeneity test and integrated analysis for the abstracted data of the eligible studies were conducted using Review Manager Statistic Software. Combined RR value was used as the index for total effect on each project for Meta-analysis. RESULTS: In total, 14 original research papers were included (totally 2148 subjects and 2044 controls). When comparing to the controls, the occupational exposure to mercury was significantly associated with longer menstrual period (RR = 1.82, 95% CI: 1.45-2.30), menstrual cycle delay (RR = 2.03, 95% CI: 1.74-2.37) and the changes of menstrual blood volume (RR = 2.06, 95% CI: 1.47-2.09), dysmenorrhea (RR = 2.14, 95% CI: 1.54-2.99), pregnancy-induced hypertension (RR = 2.17, 95% CI: 1.32-3.57), stillbirths (RR = 2.54, 95% CI: 1.41-4.56) and low birth weight (RR = 3.39, 95% CI: 1.38-8.33)/birth defect (RR = 2.67, 95% CI: 1.55-4.60) of their offspring (P < 0.05). CONCLUSION: Occupational exposure to mercury could cause dysfunction of the menstrual period, menstrual cycle, menstrual blood volume, as well as dysmenorrhea for female workers being exposed to mercury and inducing adverse reproductive outcomes, including pregnancy-induced hypertension, stillbirth, low birth weight and birth defects of their offspring.

[The effect of cadmium pollution on reproductive health in females].

OBJECTIVE: To study the relationship between cadmium pollution and its adverse effects on female reproductive health status in people living in cadmium polluted area in Zhenghe, Fujian provinces. METHODS: Data through laboratory studies on reproductive health of female residents in Cd-pollution area were studied and compared with those in control areas in Zhenghe. RESULTS: Both prevalence rates of abnormal menstrual cycle and dysmenorrhea in unmarried women in Cd-pollution area (19.1% vs. 42.6%) were significantly higher than those in control area (5.7% vs. 18.9%) and the rates of sterility in married women in Cd-pollution area (6.3%) were significantly higher than those in control area (1.1%). During the first two pregnancies, rates of queasiness, disgorgement, spontaneous abortion and stillbirth in married women in polluted area were 44.7%, 31.7%, 10.27% and 4.23%, significantly higher than those 26.5%, 17.8%, 2.85% and 1.05% in control area, with significant differences (P < 0.05). Results from cumulative odds model analysis showed that: living in Cd-pollution area was a possible risk factor related to female reproductive health (OR = 2.072), after the other risk factors being under control. CONCLUSION: The female reproductive health status of people residing in the cadmium polluted area had already been deteriorated.

Imaging of membranous dysmenorrhea.

Membranous dysmenorrhea is an unusual clinical entity. It is characterized by the expulsion of huge fragments of endometrium during the menses, favored by hormonal abnormality or drug intake. This report describes a case with clinical, US, and MRI findings before the expulsion. Differential diagnoses are discussed.

Membranous dysmenorrhea: the forgotten entity.

BACKGROUND: Membranous dysmenorrhea involves the spontaneous slough of the endometrium in one cylindrical or membranous piece that retains the shape of the uterine cavity. Because this entity is rarely mentioned in the medical literature, the purpose of this report is to describe two such cases. CASES: An 18-year-old nullipara with regular menstrual cycles presented with membranous dysmenorrhea after taking the contraceptive Gynera (Gestodene 0.075 mg, ethinyl estradiol 0.030 mg). Symptoms disappeared when the medication was discontinued. The second patient, a 26-year-old woman, gravida 1, para 1, was on a 10-day monthly regimen of Provera (medroxyprogesterone acetate) 2.5 mg/day for dysfunctional uterine bleeding. When the Provera dose was increased to 10 mg/day, the symptoms disappeared. CONCLUSION: Membranous dysmenorrhea is "a disease of theories" with various recommended medications. When this condition is caused by iatrogenic treatment, the best approach is to discontinue the offending drug or change its dosage.

Hormonal and cytopathological changes in vaginal and cervical smears from women undergoing chemotherapy for extragenital malignant diseases.

The effects of various chemotherapeutic drugs on the squamous epithelium of the cervicovaginal tissues were investigated in a test group of 74 and a control group of 44 women with advanced extragenital malignancy. The cytological findings were as follows: (A) cytohormonal changes reflecting estrogenic withdrawal in pre- and postmenopausal women, (B) reversible cytopathological changes reflecting a cytotoxic reaction, and (C) absence of premalignant and malignant changes.

Difficulties in taking care of business: women addicts as mothers.

This paper is devoted to a discussion of women addicts as mothers. Women who are addicted while pregnant begin their careers as mothers with extreme guilt and a sense of initial failure. Heroin becomes a mechanism for coping with the routine difficulties of childraising. Children can also act as a controlling force on their mother's addiction if she has the option to perform her mothering duties in an otherwise "normal" fashion. If the woman is being supported adequately and can be available for her children, it is possible to combine addiction and mothering. Often, however, the woman has to work outside the home (usually in criminal pursuits) and the general chaos of her life greatly impinges on her ability to fulfill her mothering duties. Children are occasionally mistreated, sometimes neglected physically, and often neglected psychologically by a mother who is frequently absent. Addicted mothers feel extreme guilt and remorse over this neglect, and often take stock of their situation when their roles as a mother is threatened; the children are being taken away physically or growing up and she is losing them to time. The woman addict most often wants "out" of the heroin life when her children and her role as mother--her last remaining option--are in jeopardy.