Effectiveness of Zhenqi Buxue Oral Liquid Combined with Progesterone for Treatment of Oligomenorrhea and Hypomenorrhea with Qi-Blood and Kidney (Shen) Essence Deficiency: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effectiveness and safety of Zhenqi Buxue Oral Liquid (ZQ), progesterone capsules, and their combination in treating oligomenorrhea and hypomenorrhea with qi-blood and Kidney (Shen) essence deficiency. METHODS: This was a prospective, randomized, multi-center controlled trial between June 2022 to December 2022. Ninety-six oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency were randomly assigned to receive ZQ (ZQ group, 29 cases), progesterone capsules (PG group, 32 cases), or the combined Chinese and Western medicine (COM group, 31 cases) at a ratio of 1:1:1. Patients in the ZQ or PG group took daily 10 mL twice a day of ZQ or 200 mg once a day of progesterone capsules for 10 consecutive days on day 15 of the menstrual cycle respectively, and patients in the COM group received the same ZQ combined with progesterone capsules. The treatment course lasted for 3 months and follow-up was performed at 1 and 3 months after the end of treatment. Primary endpoint was the menstrual Traditional Chinese Medicine Syndrome Scale (TCMSS) scores. Secondary endpoints included pictorial blood loss assessment chart (PBAC) scores, clinical efficacy rate, 36-item Short Form Health Survey (SF-36) scores, sex hormones and thickness of endometrium. Adverse events (AEs) were recorded. RESULTS: TCMSS scores after 1- and 3-month treatment in all groups were significantly lower than those at baseline (P<0.05). Only TCMSS scores after 3-month treatment in the ZQ and COM groups continuously decreased compared with those after 1-month treatment in the same group (P<0.01). TCMSS scores after 3-month treatment in the ZQ and COM groups were significantly lower than those in the PG group (P<0.05, P<0.01). Compared with baseline, PBAC scores in the ZQ and COM groups after 3 months of treatment were also significantly higher (both P<0.01). The total effective rates of TCM syndrome of 3-month treatment were significantly improved in all groups compared with that after 1 month of treatment (P<0.05). The total effective rate of the COM group was the highest in the 3rd month of treatment and significantly higher than that of PG group alone (P<0.05). Compared with baseline, only the SF-36 scores of COM group were significantly improved after 3 months of treatment (P<0.05). No serious adverse reactions were observed after treatment. CONCLUSIONS: The combination of ZQ and PG, or ZQ only had better effects on reducing TCMSS scores compared with PG, and COM showed the higher total effective rate compared with monotherapy. Besides, COM could effectively improve menstrual blood loss and quality of life. ZQ combined with PG may be an effective and safe option for oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency.

Effectiveness of Zhenqi Buxue Oral Liquid Combined with Progesterone for Treatment of Oligomenorrhea and Hypomenorrhea with Qi-Blood and Kidney (Shen) Essence Deficiency: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the effectiveness and safety of Zhenqi Buxue Oral Liquid (ZQ), progesterone capsules, and their combination in treating oligomenorrhea and hypomenorrhea with qi-blood and Kidney (Shen) essence deficiency.@*METHODS@#This was a prospective, randomized, multi-center controlled trial between June 2022 to December 2022. Ninety-six oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency were randomly assigned to receive ZQ (ZQ group, 29 cases), progesterone capsules (PG group, 32 cases), or the combined Chinese and Western medicine (COM group, 31 cases) at a ratio of 1:1:1. Patients in the ZQ or PG group took daily 10 mL twice a day of ZQ or 200 mg once a day of progesterone capsules for 10 consecutive days on day 15 of the menstrual cycle respectively, and patients in the COM group received the same ZQ combined with progesterone capsules. The treatment course lasted for 3 months and follow-up was performed at 1 and 3 months after the end of treatment. Primary endpoint was the menstrual Traditional Chinese Medicine Syndrome Scale (TCMSS) scores. Secondary endpoints included pictorial blood loss assessment chart (PBAC) scores, clinical efficacy rate, 36-item Short Form Health Survey (SF-36) scores, sex hormones and thickness of endometrium. Adverse events (AEs) were recorded.@*RESULTS@#TCMSS scores after 1- and 3-month treatment in all groups were significantly lower than those at baseline (P<0.05). Only TCMSS scores after 3-month treatment in the ZQ and COM groups continuously decreased compared with those after 1-month treatment in the same group (P<0.01). TCMSS scores after 3-month treatment in the ZQ and COM groups were significantly lower than those in the PG group (P<0.05, P<0.01). Compared with baseline, PBAC scores in the ZQ and COM groups after 3 months of treatment were also significantly higher (both P<0.01). The total effective rates of TCM syndrome of 3-month treatment were significantly improved in all groups compared with that after 1 month of treatment (P<0.05). The total effective rate of the COM group was the highest in the 3rd month of treatment and significantly higher than that of PG group alone (P<0.05). Compared with baseline, only the SF-36 scores of COM group were significantly improved after 3 months of treatment (P<0.05). No serious adverse reactions were observed after treatment.@*CONCLUSIONS@#The combination of ZQ and PG, or ZQ only had better effects on reducing TCMSS scores compared with PG, and COM showed the higher total effective rate compared with monotherapy. Besides, COM could effectively improve menstrual blood loss and quality of life. ZQ combined with PG may be an effective and safe option for oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency.

Efficacy of a Herbal Formulation Based on Foeniculum Vulgare in Oligo/Amenorrhea: A Randomized Clinical Trial.

BACKGROUND: The aim of this study was to evaluate the efficacy of the herbal tea based on Foeniculum vulgare, on inducing regular bleeding in women with oligomenorrhea and secondary amenorrhea( oligo/amenorrhea). METHODS: Forty women aged 18- 40 with oligo/amenorrhea were enrolled in this randomized controlled clinical trial and were allocated to two groups equally. The women in the first group were treated by Fomentex (Foeniculum vulgare / Mentha longifolia / Vitex agnus-castus) herbal tea 11.2 g/day in 2 divided doses for 2 weeks and the second group were treated by medroxy progesterone acetate (MP)10 mg/day for the last 10 days of their menstrual cycles. The intervention was repeated in three cycles of menstruation in both groups. Bleeding pattern was documented by the patient on diary cards. The occurrence (yes/no) of bleeding, the regularity of bleeding pattern, the interval of cycles, the duration of bleeding, the volume of blood flow, the hormonal parameters (total testosterone, free testosterone luteinizing hormone and follicle-stimulating hormone), and the endometrial thickness in sonography before and after the intervention were evaluated and compared as outcomes. RESULTS: The number of women with bleeding during the first cycle was in the Fomentex group and the MP group 83.3% and 94.1% respectively (p = 0.61). The regularity of bleeding did not significantly differ in patients treated with Fomentex from those given MP (66.7% vs. 94.1%; p = 0.088). Mean interval of cycles decreased in both groups after intervention (P<0.001). Mean duration decreased significantly in MP group after the intervention but it was not different in patients treated with Fomentex. The difference between 2 groups was not significant (P=0.705). Volume of blood flow, with regard to Pictorial Blood Assessment Chart (PBAC), increased significantly in MP group after the intervention (P=0.001) and it was not different in patients treated with Fomentex (P=0.757); however, difference between 2 groups was not significant (P=0.063). The percentage of patients with on time menstruation in the next (drug-free) episode, was higher in the Fomentex group compared with the MP group (50% vs. 23.5%; p = 0.105). Secondary outcomes such as dysmenorrhea, acne and hirsutism reduced in the Fomentex group (P≤0.05), while they increased in the MP group (P=0.007). At the end of the treatment, there was a significant decrease in luteinizing hormone, total testosterone and free testosterone in patients taking Fomentex. The decrease of endometrial thickness, was significant in both groups after the intervention (P=0.001), but the difference between 2 groups was not significant (P=0.58). No notable complication or side effect was reported in relation to Fomentex. CONCLUSION: Fomentex herbal tea is a safe, well-tolerated, and effective choice in inducing bleeding and maintaining regular bleeding in women with oligo/amenorrhea.

Impact of Route of Estrogen Administration on Bone Turnover Markers in Oligoamenorrheic Athletes and Its Mediators.

OBJECTIVE: Transdermal, but not oral, estrogen replacement improves bone mineral density (BMD) in athletes with oligoamenorrhea (OA). Our objective was to determine mechanisms that may explain the impact of route of estrogen administration on bone outcomes. METHODS: Seventy-three participants with OA between 14 and 25 years old received (i) a 17ß-estradiol transdermal patch continuously with cyclic oral micronized progesterone (PATCH), (ii) a combined ethinyl estradiol and desogestrel pill (PILL), or (iii) no estrogen/progesterone (NONE) for 12 months. We evaluated morning fasting levels of a marker of bone formation [N-terminal propeptide of type 1 procollagen (P1NP)], a marker of bone resorption (N-telopeptide), IGF-1, insulinlike growth factor binding protein 3, total testosterone, estradiol, SHBG, sclerostin, preadipocyte factor-1 (Pref-1), brain-derived neurotrophic factor (BDNF), calcium, 25(OH) vitamin D, and PTH levels at baseline and 12 months. RESULTS: Groups did not differ for age, weight, exercise activity, or markers of bone formation at baseline. Over 12 months, P1NP decreased the most in the PILL group (P = 0.03) associated with a decrease in IGF-1 levels (r = 0.37; P = 0.003). Sclerostin, Pref-1, and BDNF decreased in the PATCH group over 12 months. PATCH had the greatest increases in estradiol (P ≤ 0.0001), and estradiol increases were associated with increases in bone density. CONCLUSION: Transdermal 17ß-estradiol given over 12 months does not cause the decrease in IGF-1 observed with oral ethinyl estradiol. It also leads to decreases in sclerostin, Pref-1, and BDNF, which may mediate the beneficial effects of estrogen.

Herbal Medicine for Oligomenorrhea and Amenorrhea: A Systematic Review of Ancient and Conventional Medicine.

INTRODUCTION: Menstrual bleeding cessation is one of the most frequent gynecologic disorders among women in reproductive age. The treatment is based on hormone therapy. Due to the increasing request for alternative medicine remedies in the field of women's diseases, in present study, it was tried to overview medicinal plants used to treat oligomenorrhea and amenorrhea according to the pharmaceutical textbooks of traditional Persian medicine (TPM) and review the evidence in the conventional medicine. METHODS: This systematic review was designed and performed in 2017 in order to gather information regarding herbal medications of oligomenorrhea and amenorrhea in TPM and conventional medicine. This study had several steps as searching Iranian traditional medicine literature and extracting the emmenagogue plants, classifying the plants, searching the electronic databases, and finding evidences. To search traditional Persian medicine references, Noor digital library was used, which includes several ancient traditional medical references. The classification of plants was done based on the repetition and potency of the plants in the ancient literatures. The required data was gathered using databases such as PubMed, Scopus, Google Scholar, Cochrane Library, Science Direct, and web of knowledge. RESULTS: In present study of all 198 emmenagogue medicinal plants found in TPM, 87 cases were specified to be more effective in treating oligomenorrhea and amenorrhea. In second part of present study, where a search of conventional medicine was performed, 12 studies were found, which had 8 plants investigated: Vitex agnus-castus, Trigonella foenum-graecum, Foeniculum vulgare, Cinnamomum verum, Paeonia lactiflora, Sesamum indicum, Mentha longifolia, and Urtica dioica. Conclusion. Traditional Persian medicine has proposed many different medicinal plants for treatment of oligomenorrhea and amenorrhea. Although just few plants have been proven to be effective for treatment of menstrual irregularities, the results and the classification in present study can be used as an outline for future studies and treatment.

Effects of myo-inositol, gymnemic acid, and L-methylfolate in polycystic ovary syndrome patients.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder, characterized by chronic anovulation/oligomenorrhea, hyperandrogenism, and insulin-resistance. Moreover, some studies propose a possible association between insulin resistance and hyperhomocysteinemia, which is a significant long-term risk for factor for atherogenesis and chronic vascular damage, especially in situations where insulin levels are increased. Insulin-sensitizing agents are used in the treatment of PCOS: in fact, inositols were shown to have insulin-mimetic properties. Synergic action to myo-inositol is that of gymnemic acids that have antidiabetic, anti-sweetener, and anti-inflammatory activities. Gymnemic acid formulations have also been found useful against obesity due to their ability to delay the glucose absorption in the blood. L-methyl-folate increases peripheral sensitivity to insulin, maintaining folatemia stable, and thus restoring normal homocysteine levels. Unlike folic acid, L-methyl folate has a higher bioavailability, no drug/food interferences, high absorption, and it is stable to UV-A exposure. The aim of our study is to compare the clinical, endocrine, and metabolic parameters in 100 PCOS women treated with myo-inositol, gymnemic acid, and l-methylfolate (Group A) or myo inositol and folic acid only (Group B), continuously for 6 months. From a clinical point of view, it was noticed a more significant improvement of the menstrual cycle regularity and a more significant reduction of BMI in Group A. Moreover, a more significant decrease of total testosterone and increase of SHBG serum levels were noticed in Group A. The metabolic assessment found a more significant decrease of total cholesterol and homocysteine levels; OGTT glycemia and insulinemia values were significantly more improved after treatment with myo-inositol + gymnemic acid. In conclusion, we can state that a good option for the treatment of PCOS is the combined administration of myo-inositol + gymnemic acid + l-methyl-folate, especially for overweight/obese patients with marked insulin resistance and with associated hyperhomocysteinemia.

Normalizing Ovulation Rate by Preferential Reduction of Hepato-Visceral Fat in Adolescent Girls With Polycystic Ovary Syndrome.

PURPOSE: Polycystic ovary syndrome (PCOS) is an increasingly prevalent disorder in adolescent girls, commonly presenting with hirsutism/oligomenorrhea, commonly treated with an oral contraceptive (OC), and commonly followed by oligoanovulatory subfertility. We tested whether an intervention targeting the reduction of hepato-visceral adiposity is followed by a higher ovulation rate than OC treatment. METHODS: This randomized, open-label, single-center, pilot proof-of-concept study (12 months on treatment, then 12 months off) was performed in adolescent girls with hirsutism and oligomenorrhea (PCOS by National Institutes of Health; no sexual activity; N = 36; mean age 16 years, body mass index 23.5 kg/m2; 94% study completion). Compared treatments were OC (ethinylestradiol-levonorgestrel) versus low-dose combination of spironolactone 50 mg/d, pioglitazone 7.5 mg/d, and metformin 850 mg/d (SPIOMET). Primary outcome was post-treatment ovulation rate inferred from menstrual diaries and salivary progesterone (12 + 12 weeks). Secondary outcomes included body composition (dual X-ray absorptiometry), abdominal fat (magnetic resonance imaging), insulinemia (oral glucose tolerance test), and androgenemia (liquid chromatography - tandem mass spectrometry). RESULTS: SPIOMET was followed by a 2.5-fold higher ovulation rate than OC (p ≤ .001) and by a 6-fold higher normovulatory fraction (71% vs. 12%; p ≤ .001); oligoanovulation risk after SPIOMET was 65% lower (95% confidence interval, 40%-89%) than after OC. Higher post-treatment ovulation rates related to more on-treatment loss of hepatic fat (r2 = .27; p < .005). Visceral fat and insulinemia normalized only with SPIOMET; androgenemia normalized faster with OC but rebounded more thereafter. Body weight, lean mass, and abdominal subcutaneous fat mass remained stable in both groups. CONCLUSIONS: Early SPIOMET treatment for PCOS normalized post-treatment ovulation rates more than OC. Focusing PCOS treatment on early reduction of hepato-visceral fat may prevent part of later oligoanovulatory subfertility.

The role of oligomenorrhea in melasma.

Melasma is a facial hyperpigmentation in the upper lips, cheeks, forehead and chin. It is mostly seen in women. Melasma treatments include topical methods that are not only costly, but also temporary. Melasma recurs shortly after cessation of the treatment. Considering the relationship between melasma and elevated estrogen levels in patients with oligomenorrhea, systemic anti-estrogen therapies are not used for melasma. In this study, by searching in the scientific databases such as Scopus, Pubmed and the authentic books of traditional medicine such as the Canon of medicine, melasma treatment was evaluated based on oligomenorrhea systemic therapy. The results of this study showed that if melasma is due to oligomenorrhea, the use of systemic anti-estrogenic therapies can improve melasma by reducing of Melanogenesis due to decreasing α msh (alpha-Melanocyte-stimulating hormone) in addition to oligomenorrhea improvement. However, because of the extreme attention to the advertising cosmetic creams, attention to systemic therapies has been faded. According to traditional medicine, the use of menstruation-inducing systemic therapies can be more effective in melasma than topical treatments because of removing of the disease agent. Given the important role of oligomenorrhea in creating of melasma, it is suggested conducting more studies on the effect of systemic therapy of oligomenorrhea on melasma treatment. If proven, to be considered as the treatment strategies for this disease.

Estrogen Replacement Improves Verbal Memory and Executive Control in Oligomenorrheic/Amenorrheic Athletes in a Randomized Controlled Trial.

OBJECTIVE: Both estrogen and exercise may have cognition enhancing benefits; however, young oligomenorrheic/amenorrheic athletes (OA) with estrogen deficiency have not been evaluated for cognitive deficits. Our objective was to determine whether 6 months of estrogen replacement will impact cognitive domains in OA. We hypothesized that estrogen replacement would improve verbal memory and executive control in OA. METHODS: We performed cognitive assessments at baseline and after 6 months in 48 OA (14-25 years) randomized to estrogen (EST+) (oral 30 µg ethinyl estradiol [n = 16] or transdermal 100 µg 17-ß-estradiol patch [n = 13]) or no estrogen (EST-) (n = 19) in an ongoing clinical trial. Neurocognitive testing included California Verbal Learning Test-Second Edition (CVLT-II) (for verbal memory) and Delis-Kaplan Executive Function System Color-Word Interference Test (D-KEFS-CWIT) (executive control). RESULTS: On average, subjects (mean ± SEM age: 19.9 ± 3.1 years, body mass index: 20.6 ± 2.3 kg/m²) participated in 10.3 ± 5.9 hours per week of weight-bearing activities of their lower limbs. The EST+ group performed better for CVLT-II verbal memory scores for immediate recall over 6 months of therapy compared to EST- (P < .05) even after controlling for baseline scores and age. Changes in D-KEFS-CWIT scores over 6 months did not differ between the groups. However, the EST+ group had greater improvements in inhibition-switching completion time over 6 months compared with the EST- group after controlling for baseline scores and age (P = .01). CONCLUSIONS: OA show improvements in verbal memory and executive control following 6 months of estrogen replacement. These findings in athletes, who are in their prime of neurocognitive development, underscore the need for future studies exploring cognition in OA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00946192.

Standardised versus individualised multiherb Chinese herbal medicine for oligomenorrhoea and amenorrhoea in polycystic ovary syndrome: a randomised feasibility and pilot study in the UK.

OBJECTIVES: To explore feasibility of a randomised study using standardised or individualised multiherb Chinese herbal medicine (CHM) for oligomenorrhoea and amenorrhoea in women with polycystic ovary syndrome (PCOS), to pilot study methods and to obtain clinical data to support sample size calculations. DESIGN: Prospective, pragmatic, randomised feasibility and pilot study with participant and practitioner blinding. SETTING: 2 private herbal practices in the UK. PARTICIPANTS: 40 women diagnosed with PCOS and oligomenorrhoea or amenorrhoea following Rotterdam criteria. INTERVENTION: 6 months of either standardised CHM or individualised CHM, 16 g daily taken orally as a tea. MAIN OUTCOME MEASURES: Our primary objective was to determine whether oligomenorrhoea and amenorrhoea were appropriate as the primary outcome measures for the main study. Estimates of treatment effects were obtained for menstrual rate, body mass index (BMI), weight and hirsutism. Data were collected regarding safety, feasibility and acceptability. RESULTS: Of the 40 participants recruited, 29 (72.5%) completed the study. The most frequently cited symptoms of concern were hirsutism, weight and menstrual irregularity. Statistically significant improvements in menstrual rates were found at 6 months within group for both standardised CHM (mean difference (MD) 0.18±0.06, 95% CI 0.06 to 0.29; p=0.0027) and individualised CHM (MD 0.27±0.06, 95% CI 0.15 to 0.39; p<0.001), though not between group (p=0.26). No improvements were observed for BMI nor for weight in either group. Improvements in hirsutism scores found within group for both groups were not statistically significant between group (p=0.09). Liver and kidney function and adverse events data were largely normal. Participant feedback suggests changing to tablet administration could facilitate adherence. CONCLUSIONS: A CHM randomised controlled trial for PCOS is feasible and preliminary data suggest that both individualised and standardised multiherb CHMs have similar safety profiles and clinical effects on promoting menstrual regularity. These data will inform the design of a study in primary care that will incorporate an appropriate control. TRIAL REGISTRATION NUMBER: ISRCTN 31072075; Results.

Influence of the conclusion of a recent large cooperative study in changing standard protocol of inducing menses in anovulatory women with oligomenorrhea prior to initiating ovulation induction with anti-estrogens and outcome.

PURPOSE: To compare pregnancy rates following ovulation induction in anovulatory women with clomiphene citrate vs. letrozole and to determine the relative confounding effect of inducing menses or not. The study also evaluated whether starting these anti-estrogen drugs later in the menstrual cycle has-less adverse effect on endometrial thickness. MATERIALS AND METHODS: Prospective series with choice by physician of inducing menses or not or choosing clomiphene citrate or letrozole for ovulation induction. Peak endometrial thickness was compared between drugs and between those conceiving or not. RESULTS: There were 21 first cycles using letrozole and 42 using clomiphene. Menses were not induced in 18/21 (86%) letrozole cycles and 24/42 (57%) clomiphene cycles. Clinical pregnancies occurred in four (22.2%) letrozole cycles without induced menses with one miscarriage vs. 4/24 (16.6%) clomiphene cycles, no mis- carriage. One of three (33.3%) letrozole cycles with menses induced achieved a clinical pregnancy vs. only 1/18 (5.5%) of clomiphene cycles. There were no miscarriages. CONCLUSIONS: Though the endometrial thickness was higher with clomiphene without induced menses vs. menses induced (11 mm vs. 9.5 mm), one cannot explain the trend for lower pregnancy rates in women with induced menses because of thinner endometria since the thickness was 10.3 mm for clomiphene and 10.0 with letrozole.

Comparison of spironolactone and spironolactone plus metformin in the treatment of polycystic ovary syndrome.

The aim of this study was to evaluate and compare the effects of spironolactone and spironolactone plus metformin treatments on body mass index (BMI), hirsutism score, hormone levels, and insulin resistance in women with polycystic ovary syndrome (PCOS). Thirty-seven patients with PCOS were randomly assigned to receive spironolactone 100 mg/d (spironolactone group, 18 patients) or spironolactone 100 mg/d plus metformin 2000 mg/d (combination group, 19 patients) for 12 months. BMI, modified Ferriman-Gallway score (FGS), serum levels of regarding hormones, and homeostasis model assessment of insulin resistance (HOMA-IR) index were assessed before and after the treatments. Six patients in the spironolactone group and four patients in the combination group reported inter-menstrual vaginal bleeding during treatments. In hirsutism scores, the spironolactone therapy resulted in 25.2% reduction, while combination therapy resulted in 28.3% reduction (p > 0.05, between groups). When the groups were compared in terms of percent changes in BMI, FGS, HOMA-IR, and hormone values other than free testosterone, no significant difference was noted. In the present study, FGSs were significantly decreased in both groups; however, combination therapy was not more effective than spironolactone alone in terms of BMI, FGS, hormone levels, or insulin resistance.

A randomized controlled trial evaluating the effect of ethinyl estradiol during clomiphene citrate cycles among women with polycystic ovary syndrome.

OBJECTIVE: To investigate the effects of low-dose ethinyl estradiol (EE) on the clinical pregnancy rate among women with polycystic ovary syndrome (PCOS) undergoing ovulation induction with clomiphene citrate (CC). METHODS: Between March 12, 2011, and February 10, 2013, a randomized, double-blind, placebo-controlled trial was conducted at the Royan Institute Research Center, Tehran, Iran, among women with PCOS who were aged 25-30 years, were undergoing their first intrauterine insemination cycle, and had a history (≥2 years) of infertility, oligomenorrhea, or amenorrhea. Participants were randomly allocated to receive EE (0.05 mg daily for 5 days) or placebo, co-administered with CC cycles (100 mg daily for 5 days). The primary outcome was clinical pregnancy rate. Analyses were per protocol: patients who discontinued the intervention were excluded. RESULTS: Analyses included 45 women who received CC and EE, and 50 women who received CC and placebo. The number of women who achieved a clinical pregnancy was higher among participants who received CC and EE (13 [29%]) than among those in the control group (5 [10%]; P =0 .02). No adverse effects of EE were reported. CONCLUSION: The combination of CC and EE seems to increase the clinical pregnancy rate among women with PCOS undergoing intrauterine insemination. ClinicalTrials.gov:NCT01219101.

[Vitex Agnus Castus in the treatment of hyperprolactinemia and menstrual disorders - a case report]. / Vitex Agnus Castus w leczeniu hiperprolaktynemii i zaburzen cyklu miesiaczkowego - opis przypadku.

We describe a patient with mild hyperprolactinemia and menstrual disorders (oligomenorrhea). She presented relative hypoestrogenism in laboratory tests. Magnetic resonans excluded the presence of pituitary adenoma. Because patient developed a bromocriptine intolerance, the Vitex Agnus Castus (VAC) extract has been introduced. The VAC therapy was effective, with symptoms relief and improvement of hormonal tests. The VAC medicines are indicated for the treatment of premenstrual syndrome (PMS), mastalgia, menstrual disorders and mild hyperprolactinemia. The mechanism of action is not fully understood, but it is related to dopaniergic activity of diterpenes and castacin in VAC. The randomized clinical trials revealed efficacy of VAC extract in the treatmet of hyperprolactinemia, menstrual disorders, PMS and mastalgia. Good tolerability, lack of serious side-effects and drug interactions are the advantages of the VAC preparations.

Myo-inositol vs. D-chiro inositol in PCOS treatment.

AIM: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women in fertile age. It is an endocrine and metabolic disorder characterized by oligo-anovulation, hyperandrogenism and insulin-resistance. Various therapeutic approaches have been attempted in PCOS, including diet and the use of pharmacological agents such as oral contraceptives (OCs) or anti-androgens. Recently, the introduction of inositol in the treatment plan has proved to be as reasonable as useful in countering the endocrine-metabolic disorders of this syndrome. METHODS: The aim of our study was to compare the clinical, endocrine and metabolic response after 6 months of therapy in 137 PCOS women characterized by oligomenorrhea and/or acne and/or mild hirsutism and insulin-resistance. The patients were treated with myo-inositol or with D-chiro-inositol or with placebo. RESULTS: Our study showed that both myo-inositol (MI-PG) and D-chiro inositol (DCI-PG) treatments are able to significantly improve the regularity of the menstrual cycle, the Acne Score, the endocrine and metabolic parameters and the insulin-resistence in young, overweight, PCOS patients. CONCLUSION: Definitely, we assumed that both treatments with myo-inositol and with D-chiro inositol could be proposed as a potential valid therapeutic approach for the treatment of patients with PCOS. Additionally, further examination and for a longer period of treatment are needed.

Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a prevalent, complex endocrine disorder characterised by polycystic ovaries, chronic anovulation and hyperandrogenism leading to symptoms of irregular menstrual cycles, hirsutism, acne and infertility. Evidence based medical management emphasises a multidisciplinary approach for PCOS, as conventional pharmaceutical treatment addresses single symptoms, may be contra-indicated, is often associated with side effects and not effective in some cases. In addition women with PCOS have expressed a strong desire for alternative treatments. This review examines the reproductive endocrine effects in PCOS for an alternative treatment, herbal medicine. The aim of this review was to identify consistent evidence from both pre-clinical and clinical research, to add to the evidence base for herbal medicine in PCOS (and associated oligo/amenorrhoea and hyperandrogenism) and to inform herbal selection in the provision clinical care for these common conditions. METHODS: We undertook two searches of the scientific literature. The first search sought pre-clinical studies which explained the reproductive endocrine effects of whole herbal extracts in oligo/amenorrhoea, hyperandrogenism and PCOS. Herbal medicines from the first search informed key words for the second search. The second search sought clinical studies, which corroborated laboratory findings. Subjects included women with PCOS, menstrual irregularities and hyperandrogenism. RESULTS: A total of 33 studies were included in this review. Eighteen pre-clinical studies reported mechanisms of effect and fifteen clinical studies corroborated pre-clinical findings, including eight randomised controlled trials, and 762 women with menstrual irregularities, hyperandrogenism and/or PCOS. Interventions included herbal extracts of Vitex agnus-castus, Cimicifuga racemosa, Tribulus terrestris, Glycyrrhiza spp., Paeonia lactiflora and Cinnamomum cassia. Endocrine outcomes included reduced luteinising hormone (LH), prolactin, fasting insulin and testosterone. There was evidence for the regulation of ovulation, improved metabolic hormone profile and improved fertility outcomes in PCOS. There was evidence for an equivalent effect of two herbal medicines and the pharmaceutical agents bromocriptine (and Vitex agnus-castus) and clomiphene citrate (and Cimicifuga racemosa). There was less robust evidence for the complementary combination of spirinolactone and Glycyrrhiza spp. for hyperandrogenism. CONCLUSIONS: Preclinical and clinical studies provide evidence that six herbal medicines may have beneficial effects for women with oligo/amenorrhea, hyperandrogenism and PCOS. However the quantity of pre-clinical data was limited, and the quality of clinical evidence was variable. Further pre-clinical studies are needed to explain the effects of herbal medicines not included in this review with current clinical evidence but an absence of pre-clinical data.

Improving the prognosis ways of central genesis and management option in infertile women.

To study central genesis of disfunctional menstrual disorders was based particulary on electroencephalography and find out efficacy of pathogenetic management in infertile women with central forms of oligomenorrhoea and amenorrhoea compared to generally accepted hormone therapy. Depending on received management, all 159 patients were divided into two groups. Group I included 93 women with infertility and menstrual disorders treated by taking into account the found cerebral dysfunction. Group II included 66 women received generally accepted hormone therapy. 26 women belonged to group I were found to have regulated menstrual cyclicity (28%) after neuro-mediatorical management with tegretol, finlepsin, cinnarizin, phenazepam,- received during 3-6 months. In group II, in 3 women (4.5%) was obtained improvement and period became regular by using hormone treatment, included Diane-35, Tri-Regol, Marvelon subsequently by generally accepted way during long lasting courses (12 months- more than 1 year). Pregnancy occurred in 17 cases in group I (18.3%). The difference was significantly higher in this group in comparison with group II, where pregnancy was attained only in 3 women (4.5%). Our findings indicate that in the basis of menstrual disorders observed in 159 infertile women were stood dysfunctional changes of central regular mechanisms. Pathogenetic therapy showed that we have taken into consideration neuro-mediatorical correction of found central nervous system level dysfunction. By this way our study reveals significant success of management with neuro-mediatorical purpose compared to the generally accepted hormone therapy.

Management of anovulatory infertility.

Anovulatory subfertility is a heterogeneous condition with various underlying causes, which should be identified with appropriate history taking, physical examination and relevant investigations. Optimisation of body weight is essential in either underweight, overweight or obese individuals. Women with hypogonadotrophic anovulation can be treated with pulsatile gonadotrophin-releasing hormone therapy or a gonadotrophin preparation containing both follicle-stimulating hormone or luteinising hormone activities. For normogonadotrophic anovulation, clomiphene citrate should be used as first-line medical treatment. Metformin co-treatment with clomiphene citrate may be considered in a subgroup of women with polycystic ovary syndrome who are obese or clomiphene-resistant. Ovulation induction with gonadotrophin or laparoscopic ovarian drilling is the next option. Dopamine agonist is indicated for anovulation as a result of hyperprolactinaemia.

Early metformin therapy (age 8-12 years) in girls with precocious pubarche to reduce hirsutism, androgen excess, and oligomenorrhea in adolescence.

CONTEXT: Girls with a combined history of low(-normal) birth weight (LBW) and precocious pubarche (PP) are at high risk to develop polycystic ovary syndrome (PCOS). OBJECTIVE: The objective of the study was to compare the capacity of early vs. late metformin treatment to prevent adolescent PCOS. DESIGN: This was a randomized, open-label study over 7 yr. SETTING: The study was conducted at a university hospital. PATIENTS: Thirty-eight LBW-PP girls were followed up from the mean age 8 until age 15 yr. INTERVENTION: Early metformin (study yr 1-4; age 8-12 yr) vs. late metformin (yr 6; age 13-14 yr). MAIN OUTCOME MEASURES: Measures included height; weight; hirsutism score; menstrual cycle; endocrine-metabolic screening (fasting; follicular phase); C-reactive protein; body composition (absorptiometry); abdominal fat partitioning (magnetic resonance imaging); ovarian morphology (ultrasound); PCOS (National Institutes of Health and Androgen Excess Society definitions) after yr 7 (all girls thus untreated for at least 1 yr). RESULTS: None of the girls dropped out of the study. At age 15 yr, early-metformin girls were taller (4 cm), were in a less proinflammatory state, and had less central fat due to reductions in visceral and hepatic fat. Hirsutism, androgen excess, oligomenorrhea, and PCOS were between 2- and 8-fold more prevalent in late- than early-treated girls. Abdominal adiposity was the first variable to diverge (at age 8-10 yr) between girls without vs. with PCOS at age 15 yr. CONCLUSIONS: In LBW-PP girls, early metformin therapy was found to prevent or delay the development of hirsutism, androgen excess, oligomenorrhea, and PCOS more effectively than late metformin. The time window of late childhood and early puberty may be more critical for the development, and thus for the prevention, of adolescent PCOS than the first years beyond menarche.