Omega-3 long chain polyunsaturated fatty acids as a potential treatment for reducing dysmenorrhoea pain: Systematic literature review and meta-analysis.

AIM: This systematic literature review with meta-analysis aimed to determine the effect of omega-3 long chain polyunsaturated fatty acids on prostaglandin levels and pain severity in women with dysmenorrhoea and identify adverse side effects. METHODS: A literature search was conducted in Embase, Scopus, Web of Science, MEDLINE complete, CINAHL and AMED databases (PROSPERO CRD42022340371). Included studies provided omega-3 long chain polyunsaturated fatty acids compared to a control in women with dysmenorrhoea and reported pain and/or prostaglandin levels. A random effects meta-analysis with Cohen's d effect size (95% confidence interval) was performed in SPPS for studies that reported pain outcomes. Study quality was assessed using the Academy of Nutrition and Dietetics Quality Criteria Checklist. RESULTS: Twelve studies (n = 881 dysmenorrhoeal women) of predominantly neutral quality (83%) were included that provided daily supplementation of 300-1800 mg omega-3 long chain polyunsaturated fatty acids over 2 or 3 months. Meta-analysis (n = 8 studies) showed a large effect of omega-3 long chain polyunsaturated fatty acids (d = -1.020, 95% confidence interval -1.53 to -0.51) at reducing dysmenorrhoea pain. No studies measured prostaglandin levels, 86% of studies measuring analgesic use showed a reduction with omega-3 long chain polyunsaturated fatty acids and few studies reported mild adverse side effects in individual participants. CONCLUSIONS: Findings suggest that daily supplementation of 300-1800 mg omega-3 long chain polyunsaturated fatty acids over 2-3 months are generally well tolerated and reduces pain and analgesic use in women with dysmenorrhoea. However, the neutral quality of research is limited by methodological issues and the mechanism of action remains to be determined.

Carvacrol-Loaded Nanoemulsion Promotes Tocolytic and Anti-Dysmenorrhea Effects in Rodents.

INTRODUCTION: Carvacrol is a phenolic constituent of essential oils that has antinociceptive, anti-inflammatory, and antioxidant activities. METHOD: This study aimed to evaluate the in vitro spasmolytic and in vivo anti-dysmenorrhea potential of a nanoemulsion-containing carvacrol (nanoCARV). RESULTS: In isolated rat uterus, nanoCARV reduced spontaneous contractions (pEC50 = 3.91 ± 0.25) and relaxed preparations pre-contracted with oxytocin (pEC50 = 3.78 ± 0.2), carbachol (pEC50 = 4.15 ± 0.4), prostaglandin F2α (pEC50 = 3.00 ± 0.36), and KCl (pEC50 = 3.98 ± 0.32). The investigation of the mechanism of action revealed significant differences (p < 0.05) between the pEC50 values of nanoCARV in the absence or presence of aminophylline or tetraethylammonium. In a primary dysmenorrhea model, treatment with nanoCARV reduced the number of oxytocin-induced abdominal writhes. CONCLUSIONS: These data indicate that the anti-dysmenorrhea effect of nanoCARV may be related to the relaxation of uterine smooth muscle, with participation of the cAMP signaling pathway and potassium channels.

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.

Multigenerational endometriosis : consequence of fetal exposure to diethylstilbestrol ?

BACKGROUND: Endometriosis, which affects 10-15 % of women of reproductive age, is an estrogen-driven condition influenced by environmental and genetic factors. Exposition to estrogen-like endocrine-disrupting chemicals (EDCs) has been reported to contribute to the fetal origin of this disease. CASE PRESENTATION: We report here an informative family in which all prenatally DES-exposed daughters and subsequent granddaughters presented endometriosis, whereas the unexposed first daughter and her progeny presented no gynecological disorders. Moreover, the only post-pubertal great-granddaughter, who presents chronic dysmenorrhea that remains resistant to conventional therapy, is at risk of developing endometriosis. The mother (I-2) was prescribed DES (30 mg/day for 3 months) to inhibit lactation after each delivery. CONCLUSIONS: Although a direct causal link between the grandmother's treatment with DES and the development of endometriosis in possibly three exposed generations remains speculative, this report strengthens the suspicion that fetal exposition to DES contributes to the pathogenesis of adult diseases, such as endometriosis. It also highlights a multigenerational and likely transgenerational effect of EDCs.

Taking Call.

Telehealth proves to be more than just a stopgap in providing support to patients.

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.

An experimental study of the anti-dysmenorrhea effect of Chinese herbal medicines used in Jin Gui Yao Lue.

ETHNOPHARMACOLOGICAL RELEVANCE: Dang-Gui-Shao-Yao-San () and Gui-Zhi-Fu-Ling-Tang () and among the herbal medicines commonly used to treat primary dysmenorrhea with proven record of effectiveness. AIM OF THIS STUDY: This study aims to assess the effectiveness of herbal medicines on relieving primary dysmenorrhea in a murine model and to delineate a plausible mechanism. MATERIALS AND METHODS: Herbal medicines in the form of pills (Wan) or capsules, including Gui-Zhi-Fu-Ling capsule, Gui-Zhi-Fu-Ling-Wan, Jia-Wei-Xiao-Yao-Wan, and Shao-Fu-Zhu-Yu capsule were purchased from local drug stores in Nanjing. Dang-Gui-Shao-Yao-San filled from a local hospital. The identity of the drugs was validated by HPLC profiling. Female ICR mice were used for an induced dysmenorrhea model. The severity of dysmenorrhea was evaluated and scored, the motor coordination and balance affected by induced dysmenorrhea was assessed by a Rotarod test. Uterine inflammation and edema were examined after histological and immunohistochemical staining. The effect of the drugs on COX2 activity was evaluated enzymatically. RESULTS: The Chinese herbal medicines at dosages relevant to recommended uses in humans relieved painful responses, including abdominal wall contraction, pelvic twisting and/or rear limb stretching. The treatment also improved motor coordination, extending the time staying on a rotating rod from 2.64 ±â€¯0.38 min of oxytocin-induced group to 8.59 ±â€¯1.45 (DGSYs), 9.50 ±â€¯1.47 (GZFLc), 8.04 ±â€¯1.87 (GZFLw), 9.91 ±â€¯1.62 (JWXYw), and 8.20 ±â€¯1.35 min (SFZYc), respectively. H&E staining showed that treatment with ibuprofen or Chinese herbal medicines markedly decreased edema and inflammatory cell infiltration in uterine tissues. The treatment did not significantly affect pattern of COX2 staining. In an in vitro enzymatic assay, the Chinese herbal medicines showed strong inhibitory activity against cyclooxygenase-2. The aqueous extracts from P. lactiflora or P. suffruticosa, two of the common components in the formulae tested, also showed anti-dysmenorrhea activity in the rotarod assay. CONCLUSION: The study demonstrates that traditionally used Chinese herbal medicines are effective against induced-dysmenorrhea. These herbal medicines relieve dysmenorrhea symptoms likely though inhibition of cyclooxygenase activity.

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.

Extracts of compound Muniziqi granule suppressed uterus contraction and ameliorated oxytocin-induced primary dysmenorrhea.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Muniziqi granule (CMG) is usually used as a traditional Uighur medicine to treat acne, chloasma, skin inflammation, primary dysmenorrhea (PDM), and menopausal syndrome. However, there are no sufficient data to support the clinic uses of CMG in PDM. AIM OF THE STUDY: This work aims to examine the effect of CMG as a treatment for PDM and reveal its possible therapeutic mechanism. MATERIALS AND METHODS: In vivo and in vitro mouse PDM models were utilized in this study. The mouse uterine contraction was induced by oxytocin after progynova or estradiol benzoate pretreatment. CMG, alkaloid extracts from seeds of Peganum harmala (AEP), and 10% and 95% ethanol extracts from seeds of Nigella glandulifera (EEN10 and EEN95) were given to mice in three doses by gavage. The writhing times within 30 min after oxytocin treatment were recorded to evaluate the analgesic effect, and the glutathione peroxidase (GSH-Px), malondialdehyde (MDA), 6-keto-prostaglandin F1α (6-k-PGF1α), prostaglandin F2α (PGF2α), thromboxane B2 (TXB2), and nitric oxide (NO) levels in uterine tissues and PGF2α and MDA in serum were determined. The effects (contractile curve) of CMG, AEP, EEN10, and EEN95 on uterus contraction induced by oxytocin in isolated mouse uterus were recorded. RESULTS: In contrast to the control group, CMG, AEP, N10, and N95 could display analgesic activities dose dependently by reducing the writhing response of the PDM model mice. CMG, AEP, EEN10, and EEN95 could also remarkably decrease the level of PGF2α, 6-k-PGF1α, TXB2, NO and MDA in uterine tissues and PGF2α and MDA in serum, whereas the activity of GSH-Px in uterine tissues was increased. Furthermore, CMG, AEP, EEN10, and EEN95 could significantly inhibit the frequency and amplitude of isolated uterus induced by oxytocin in a concentration-dependent manner. CONCLUSIONS: CMG exhibited a significant protective effect on experimental PDM. The mechanisms are probably associated with abating lipid peroxidation and over-inflammatory reaction, and alleviating the contraction of isolated mouse uterus. The seeds of P. harmala and N. glandulifera in the CMG may play an important role in exerting protective effects on PDM. This study provides pre-clinic proof to the use of CMG in clinical practice of PDM.

Efficacy and safety of the contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive in Chinese women: a 1-year randomised trial.

OBJECTIVES: The aim of the study was to assess the efficacy and tolerability of the monthly vaginal ring (NuvaRing; 15 µg ethinylestradiol [EE] and 120 µg etonogestrel per day) compared with a monophasic (21/7) combined oral contraceptive (COC) containing 30 µg EE and 3 mg drospirenone in healthy Chinese women aged 18-40 years. METHODS: This was a phase III, open-label, randomised multicentre trial conducted in China. Participants received NuvaRing or COC for 13 cycles (3 weeks of ring/pill treatment followed by a 1-week ring-free/pill-free period). Contraceptive efficacy was assessed by in-treatment pregnancies and expressed by the Pearl Index (PI; number of pregnancies/100 woman-years of use). Cycle control was assessed by unscheduled (breakthrough) and absence of scheduled (withdrawal) bleeding events. Safety and tolerability were assessed throughout the study. RESULTS: Participants were randomised either to the NuvaRing (n = 732) or to the COC (n = 214); 588 (82.4%) and 182 (78.4%) participants, respectively, completed the study. There were 10 in-treatment pregnancies in the NuvaRing group (PI 1.92; 95% confidence interval [CI] 0.92, 3.53) and five in the COC group (PI 3.12; 95% CI 1.01, 7.29). Breakthrough bleeding/spotting ranged from 18.6% (Cycle 1) to 4.2% (Cycle 11) for NuvaRing and from 21.6% (Cycle 1) to 7.9% (Cycle 11) for COC. Absence of withdrawal bleeding ranged from 8.6% (Cycle 1) to 3.0% (Cycle 11) for NuvaRing and from 14.6% (Cycle 1) to 6.4% (Cycle 5) for COC. For NuvaRing and COC, respectively, 26.6% and 25.0% of participants had treatment-related adverse events, and 7.0% and 9.1% discontinued the study as a result. CONCLUSIONS: Once-monthly NuvaRing is efficacious and safe for use in Chinese women.

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.

Evaluation of the anti-inflammatory and analgesic properties of individual and combined extracts from Commiphora myrrha, and Boswellia carterii.

AIM OF THE STUDY: The Chinese herbs of myrrh and frankincense are often combined for treating some inflammatory pain diseases with synergistic therapeutic effects. In this study, we investigated the effects of individual herbal extracts and combined extract on anti-inflammatory and analgesic activities in vivo and analyzed the potential bioactive components from the combination extract by ultra-performance liquid chromatography coupled with mass spectrum (UPLC-MS/MS). MATERIALS AND METHODS: The anti-inflammatory activities were investigated by utilizing the paw edema mice induced by formalin and carrageenan. In addition, we determined the levels of PGE(2) and nitrite in the edema paw. The analgesic activity was examined against oxytocin-induced dysmenorrhea in mice. The effects of the administration of dolantin or indomethacin were also studied for references. The components in combination extract (CWE) were analyzed by UPLC-MS/MS. RESULTS: The results showed that myrrh water extract (MWE) and the combined extract (CWE) at the 3.9 g/kg, and 5.2 g/kg showed inhibition of formalin-induced paw edema with inhibition rate of 30.44%, and 23.50%, respectively. The PGE(2) production was inhibited significantly by all samples (P<0.01 or P<0.05). CWE showed stronger suppression on carrageenan-induced mice paw edema at 2 and 3h after administration of drugs. The inhibitory effect of CWE on nitrite production was between that of MWE and water extract of frankincense (FWE) at 5.2 g/kg. The dysmenorrhea mice test showed MWE could remarkably reduce the writhing times (P<0.05) and prolong the latency period, while FWE showed no obvious effects on the writhing times. CWE significantly reduced the writhing times and prolong the latency period (P<0.01). CONCLUSION: These results demonstrated MWE, FWE, and CWE exhibited significant anti-inflammatory and analgesic activities. The findings suggest that CWE may be therapeutically more useful for mitigating inflammatory pain than individual herbal extract. In addition, 12 potential active compounds were identified from CWE. These data may support the fact the traditional application of this combined extract in treating various diseases associated with inflammatory pain.

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.

Long-term efficacy and safety of a monophasic combined oral contraceptive containing 0.02 mg ethinylestradiol and 2 mg chlormadinone acetate administered in a 24/4-day regimen.

OBJECTIVE: This study was conducted to assess the long-term efficacy and safety of a low-dose monophasic combined oral contraceptive (COC) containing 0.02 mg ethinylestradiol (EE) and 2 mg chlormadinone acetate (CMA) in a novel regimen administered daily for 24 days followed by a 4-day placebo interval. STUDY DESIGN: In this multicenter, uncontrolled, Phase III trial, 1665 subjects took the COC 0.02 mg EE/2 mg CMA for up to 21 cycles. The overall Pearl Index was the primary end point; cycle control, safety, effect on acne and seborrhea, and changes in body weight and libido were secondary end points. RESULTS: Contraceptive efficacy was analyzed for 1653 subjects completing 21,495 cycles. Six pregnancies occurred during trial duration with one attributable to method failure. The overall Pearl Index for the first year of use was 0.33 (95% confidence interval, 0.09-0.85). The mean number of bleeding/spotting days during six 90-day reference periods (RPs) decreased from 17.0 (RP 1) to 11.7 (RP 6), and the number of bleeding episodes per RP decreased from 3.8 (RP 1) to 2.7 (RP 6). Among subjects who presented with acne at the baseline visit, a decrease of papules/pustules and comedones was observed during the course of the trial. The most common "at least possibly related" adverse events were headache, breast discomfort and nausea. The tolerability and well-being was reported as being excellent or good in the majority of trial subjects (84.6% and 80.2%, respectively). CONCLUSIONS: The low-dose COC 0.02 mg EE/2 mg CMA administered daily for 24 days followed by a 4-day placebo interval provides high contraceptive efficacy combined with an adequate cycle control and safety profile, beneficial effects on acne, and is well tolerated.

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.