Dietary Supplementation of Lauric Acid Alleviates the Irregular Estrous Cycle and the Impaired Metabolism and Thermogenesis in Female Mice Fed with High-Fat Diet (HFD).

Lauric acid (LA) has been implicated in the prevention/treatment of obesity. However, the role of LA in modulating an obesity-related female reproductive disorder remains largely unknown. Here, female mice were fed a control diet, high-fat diet (HFD), or HFD supplemented with 1% LA. The results demonstrated that the HFD-induced estrous cycle irregularity and the reduction of serum follicle-stimulating hormone (FSH) were alleviated by LA supplementation. In possible mechanisms, LA supplementation led to significant increase in serum lipid metabolites such as sphingomyelin and lysophosphatidylcholine containing LA (C12:0) and the improvement of glucose metabolism in mice fed HFD. Moreover, impaired body energy metabolism and weakened brown adipose tissue (BAT) thermogenesis of HFD-fed mice were improved by LA supplementation. Together, these findings showed that LA supplementation alleviated HFD-induced estrous cycle irregularity, possibly associated with altered serum lipid metabolites, improved glucose metabolism, body energy metabolism, and BAT thermogenesis. These findings suggested the potential application of LA in alleviating obesity and its related reproductive disorders.

Uncovering the pharmacological mechanism of motherwort (Leonurus japonicus Houtt.) for treating menstrual disorders: A systems pharmacology approach.

Leonurus japonicus (motherwort) is a traditional Chinese medicine that is widely used to treat menstrual disorders (MDs). However, the pharmacological mechanisms that underlie its clinical application remain unclear. In this study, a network pharmacology-based approach was used that integrated drug-likeness evaluation, oral bioavailability prediction, target exploration, network construction, bioinformatic annotation and molecular docking to investigate the mechanisms that underlie motherwort treatment for MDs. In total, 29 bioactive compounds were collected from 51 compounds in motherwort, which shared 17 common MDs-related targets. Network analysis indicated that motherwort played a therapeutic role in MDs treatment through multiple components that acted on multiple targets. Pathway enrichment analysis showed that the putative targets of motherwort were primarily involved in various pathways associated with the endocrine system, cancers, vascular system, and anti-inflammation process. Notably, five targets (i.e., AKT1, PTGS2, ESR1, AR and PPARG) were screened as hub genes based on a degree algorithm. Moreover, most of the bioactive components in motherwort had good binding ability with these genes, implying that motherwort could regulate their biological function. Collectively, this study elucidated the molecular mechanisms that underlay the efficiency of motherwort against MDs and demonstrated the potential of network pharmacology as an approach to uncover the action mechanism of herbal medicines.

Regulation effect and mechanism of Sheng-Hua-Tang on female reproductive system: From experimental transcriptomic analysis to clinical applications.

ETHNOPHARMACOLOGICAL RELEVANCE: Sheng-Hua-Tang (SHT) is commonly used to treat female illnesses, especially postpartum conditioning. However, its effects and mechanisms on female reproductive system remain unclear. The aim of the present study was to investigate the effect of SHT on female brain-ovary-uterus axis from bench to clinic. MATERIALS AND METHODS: Mice were administrated SHT (200 mg/kg) orally for seven consecutive days. Brain, ovary, and uterus tissues were then collected for microarray analysis. A nationwide database analysis and a pilot randomized, open-label clinical trial were further applied to evaluate the clinical application and effects of SHT on postpartum women. RESULTS: Microarray analysis showed that oral administration of SHT induced a cascade reaction of gene expression, with 17, 883, and 1592 genes were significantly regulated by SHT in brain, ovary, and uterus, respectively. Population-based analysis of one million subjects in Taiwan's National Health Insurance Research Database between 1997 and 2013 showed that SHT was commonly used in menstrual disorders in female population, especially dysmenorrhea, abnormal uterine bleeding, and variation of menstrual cycle. Clinical trial on postpartum women showed that oral administration SHT for one week alleviated uterine contraction pain and breast swelling pain. Furthermore, Mmp2, Mmp3, Mmp9, Mmp11, Mmp15, Oxtr, Plrl, and Tph2 gene expression affected by SHT in mice were correlated with clinical effects of SHT in human subjects. CONCLUSION: This report provided the scientific evidences of mechanisms and clinical efficacies of SHT. Moreover, our findings might afford insights for clinical doctors in terms of SHT prescription.

[Pharmacodynamic evaluation and molecular mechanism research of Huanshao capsule on irregular menstruation].

Huanshao capsule is widely used in irregular menstruation and has achieved a good effect. Huanshao capsule can promote gonad development in mice, significantly improve the ovarian index in mice, increase estrogen level and reduce FSH level in rats, inhibit the pain response induced by oxytocin and estrogen, inhibit writhing reaction induced by acetic acid pain in mice. Due to the complexity of traditional Chinese medical formula, the pharmacological mechanism of the treatment on the irregular menstruation of the Huanshao capsule is unclear. In this study, the internet-based computation platform (www.tcmip.cn）was used to explore the molecular mechanism of Huanshao capsule on the menstrual. The aim of this study was to find the molecular mechanism of Huanshao capsule in treating menstrual. In the study of the molecular mechanism of Huanshao capsule in the treatment of menstrual by using the internet-based computation platform, Huanshao capsule maybe treat the menstrual by the pathway of endocrine system, GnRH signal transduction pathway, estrogen signal transduction pathway, oxytocin signaling pathway, thyroid hormone signaling pathway, VEGF signaling pathway, FCεRI signaling pathway and purine metabolism and nucleotide metabolism. The early pharmacological study confirmed Huanshao capsule could increase the serum estradiol level and decrease follicle stimulating hormone level and the traditional Chinese medicine pharmacology coincide with the prediction result of internet-based computation platform which roles as the pathway of GnRH signaling pathway and estrogen signal transduction pathway. Other pathway needs further experimental verification.

High dose vitamin D supplementation can improve menstrual problems, dysmenorrhea, and premenstrual syndrome in adolescents.

Vitamin D has a crucial role in female reproduction, possibly through its effects on calcium homeostasis, cyclic sex steroid hormone fluctuations, or neurotransmitter function. We have assessed the effects of vitamin D supplementation on dysmenorrhea and premenstrual syndrome (PMS) in adolescents. In this study, 897 adolescent girls living in Mashhad and Sabzevar, Iran, received nine high-dose vitamin D supplements (as 50,000 IU/week of cholecalciferol) and were followed up over 9 weeks. We evaluated the effect of vitamin D supplementation on individuals in four categories: those with only PMS; individuals with only dysmenorrhea; subjects with both PMS and dysmenorrhea and normal subjects. The prevalence of PMS after the intervention fell from 14.9% to 4.8% (p < .001). Similar results were also found for the prevalence of subjects with dysmenorrhea (35.9% reduced to 32.4%), and in subjects with both PMS and dysmenorrhea (32.7% reduced 25.7%). Vitamin D supplementation was associated with a reduction in the incidence of several symptoms of PMS such as backache and tendency to cry easily as well as decrement in pain severity of dysmenorrhea (p < .05). High dose vitamin D supplementation can reduce the prevalence of PMS and dysmenorrhea as well as has positive effects on the physical and psychological symptoms of PMS.

Western herbal medicine consultations for common menstrual problems; practitioner experiences and perceptions of treatment.

To explore the prevalence with which Australian Western herbalists treat menstrual problems and their related treatment, experiences, perceptions, and interreferral practices with other health practitioners. Members of the Practitioner Research and Collaboration Initiative practice-based research network identifying as Western Herbalists (WHs) completed a specifically developed, online questionnaire. Western Herbalists regularly treat menstrual problems, perceiving high, though differential, levels of effectiveness. For menstrual problems, WHs predominantly prescribe individualised formulas including core herbs, such as Vitex agnus-castus, and problem-specific herbs. Estimated clients' weekly cost (median = $25.00) and treatment duration (median = 4-6 months) covering this Western herbal medicine treatment appears relatively low. Urban-based women are more likely than those rurally based to have used conventional treatment for their menstrual problems before consulting WHs (p = .001). Only 19% of WHs indicated direct contact by conventional medical practitioners regarding treatment of clients' menstrual problems despite 42% indicating clients' conventional practitioners recommended consultation with WH. Western herbal medicine may be a substantially prevalent, cost-effective treatment option amongst women with menstrual problems. A detailed examination of the behaviour of women with menstrual problems who seek and use Western herbal medicine warrants attention to ensure this healthcare option is safe, effective, and appropriately co-ordinated within women's wider healthcare use.

Effects of icariin on the expression of ER, VEGF, and KDR in the endometrial cells of thin endometrium.

We explored the effects of icariin on the expression of estrogen receptor (ER), vascular endothelial growth factor (VEGF), and kinase insert domain receptor (KDR) in the endometrial cells of the thin endometrium. Primary endometrial cells were obtained and divided into a blank control group, a high-, a middle-, and a low-dose icariin groups, as well as an estrogen treatment group to undergo cellular identification by immunocytochemistry. The expression levels of ER, VEGF, and its receptor were estimated by western blotting. The expression levels of ER, VEGF, and KDR gradually increased from the control group to the estrogen (E2) treatment and icariin treatment groups; the differences were statistically significant. However, the differences were not statistically significant among the different icariin dose groups. The endometrium may be thickened by icariin treatment by increasing the expression levels of ER, VEGF, and KDR in endometrial cells.

Tradition in treating taboo: Folkloric medicinal wisdom of the aboriginals of Purulia district, West Bengal, India against sexual, gynaecological and related disorders.

ETHNOPHARMACOLOGICAL RELEVANCE: In order to explore the traditional medicine practised by the ethnic communities residing in the topographically and climatically challenged Purulia, an underprivileged district of West Bengal, India, a quantitative ethnobiological approach was adopted to document the folkloric use of ethnomedicinals against different sexual, gynaecological and related ailments. MATERIALS AND METHODS: Ethnobiological surveys were conducted during 2012-2015 by interviewing 82 informants or traditional healers with the help of a semi-structured questionnaire. The survey included questions on botanical and non-botanical ingredients and additives mixed with monoherbal and polyherbal formulations, vernacular names of the plants and animals, methods of preparation and administration and restrictions during medications. Additional quantitative indices such as use value, informant׳s consensus factor and fidelity level were used for data analysis. RESULTS: Twenty eight sexual and gynaecological disorders were found to be treated with 18 monoherbal and 31 polyherbal formulations consisting of a total number of 96 plant species from 86 genera and 47 families and four animal species. A variety of additives, either botanicals or non-botanicals were used with the formulations for higher efficacy and taste enhancement. Fabaceae (16 species) was found to be the most common family of medicinal plants whereas herbs (42.7%) and roots (32%) were the most common habit type and plant part used respectively. Use value, informant׳s consensus factor and fidelity level indicate frequency and coherence of citations. CONCLUSION: Age old belief on traditional medicine prevails in the studied area due to its efficacy, inexpensive price and the remoteness of tribal villages from conventional medical centres. Traditional healers had detailed knowledge of preparations, doses, methods of administration, restrictions during medications, safety and efficacy of using folkloric therapeutics against sexual and gynaecological disorders. Possible synergistic interactions among phytochemicals and additives were indicated to explain enhanced therapeutic efficacy of mixed herbal formulations.

Traditional phytoremedies for the treatment of menstrual disorders in district Udhampur, J&K, India.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal remedies form an integral part of healing and are considered to be the oldest forms of health care known to mankind. The present study aims to document traditional phytoremedies for the treatment of menstrual disorders in Udhampur district of J&K, India. MATERIAL AND METHODS: The informants were interviewed directly and information was gathered about plants used in different menstrual disorders. The data was further analyzed for use-value (UV), factor informant consensus (Fic) and fidelity level (Fl). RESULTS: In all, 62 informants were interviewed. Most of the informants (66%) were females. The patients prefer female healers over male vaids and hakims. A total of 50 plants were used to cure different menstrual disorders. Seeds were found to be of utmost medicinal importance (43.8%) followed by leaves (20.8%) and fruits (16.7%). Oral administration was observed to be the main mode (90.0%) of intake of medicine. The plants with high use-value were Triticum aestivum (UV=1.76), Taraxacum officinale (UV=1.16), Citrus limon (UV=0.95), Allium cepa (UV=0.79), Cicer arietinum (UV=0.77), Trigonella foenum-graecum (UV=0.66), Rubia manjith (UV=0.56), Ocimum tenuiflorum (UV=0.56) and Oryza sativa (UV=0.52). The various menstrual disorders were classified into 7 categories. The values of Fic varied between 0.96 (dysmenorrhea, itching and foul smell) and 0.92 (menorrhagia). The 100% Fl value was scored by 20 plants. Leucorrhea reported the highest 5 plants with 100% Fl. Nearly 40% of the formulations had two or more plants. CONCLUSION: Plants used for the treatment of different menstrual disorders were documented and analyzed for ethnogynecological problems. The study revealed some plants like Triticum aestivum, Rubia manjith, Dalbergia sissoo, Raphanus sativus, Citrus limon, Allium cepa, Trigonella foenum-graecum, Elettaria cardamomum etc. to be of great importance vis a vis menstrual disorders. Further pharmacological studies of these plants may provide some important drugs for the treatment of common menstrual disorders.

[Discussion on application of Chinese medicine treatment of gynecological diseases].

With rapid social development rhythm, the incidence of gynecological diseases gradually rise. Traditional Chinese medicine has made irreplaceable position in the treatment of gynecological disease. Due to the characteristics of gynecological diseases, the syndrome differentiation and treatment has unique characteristics. In this paper, according to menstrual disease, leukorrheal diseases, pregnancy diseases, puerperal diseases and miscellaneous diseases in order, combining documents discussion and old doctors of traditional Chinese medicine treatment of gynecological disease experiences, illustrate the key points of drug selection in the treatment process. We can get a revelation that appropriate choice of tradition Chinese medicine is an indispensable part for healing effects. Through the analysis of characteristics of drugs, we can understand the feature of each period in disease of department of gynecology, increase the ability of usinig traditional Chinese medicine and improve the level of clinical treatment.

Effects of Korean red ginseng (Panax Ginseng Meyer) on bisphenol A exposure and gynecologic complaints: single blind, randomized clinical trial of efficacy and safety.

BACKGROUND: Korean red ginseng (KRG) is a processed ginseng from raw ginseng to enhance safety, preservation and efficacy, known having beneficial effects on women's health due to its estrogen like function. While estrogen supplementation showed some modulation of endocrine disrupting chemicals, bisphenol A (BPA) has been focused as a potential endocrine disrupting chemical. In this study, we examined the efficacy and safety outcomes of KRG against BPA, focusing on female quality of life (QOL). Individual variations in susceptibility to KRG were also investigated with the Sasang Typology, the personalized medicine used for hundred years in Korea. METHODS: We performed a single-blind randomized clinical trial. Study subjects were young women (N = 22), consumed 2.7 g of KRG or placebo per day for 2 weeks and filled up questionnaires regarding gynecologic complaints at the 4 time spots. We analyzed urinary total BPA and malondialdehyde (MDA), an oxidative stress biomarker, with GC/MS and HPLC/UVD respectively, and diagnosed their Sasang Typology with the questionnaire for the Sasang constitution Classification (QSCC II). RESULTS: KRG consumption decreased urinary BPA and MDA levels (ps < 0.05) and alleviated 'menstrual irregularity', 'menstrual pain', and 'constipation' (ps < 0.05). SoEum type (Lesser Yin person) among the Sasang types showed significant alleviation in insomnia, flushing, perspiration and appetite by KRG consumption, rather than other Sasang types. During the intervention, no one experienced any aggravated side effects. CONCLUSION: We suggest KRG is efficient for protection for female QOL and BPA- exposure and - related oxidative stress. However, individual variation in susceptibility to KRG should be further considered for identifying ideal therapy. TRIAL REGISTRATION: KCT0000920.

Medicinal plants used for menstrual disorders in Latin America, the Caribbean, sub-Saharan Africa, South and Southeast Asia and their uterine properties: a review.

ETHNOPHARMACOLOGICAL RELEVANCE: Menstrual disorders are generally not perceived as major health concerns by global health organizations, despite being disruptive to women׳s daily activities, particularly when access to sanitary facilities or analgesics is limited. Improving menstrual health requires access to safe and effective medication, but many women in Latin America, Africa or Asia prefer traditional medicine above modern remedies (such as contraceptives), as they can cause physical symptoms associated with fertility loss. Many medicinal plants are used for menstrual disorders, but few have been examined for their pharmacological activities related to traditional uses. Plants that have a smooth muscle-relaxant effect could ease menstrual cramps, but there are indications that dysmenorrhea in low-income countries is commonly treated with emmenagogues. This review aims to assess the most salient plants used to treat menstrual morbidity in Latin America and the Caribbean, sub-Saharan Africa, South and Southeast Asia, their uterine properties and adverse effects. To test whether plants used for painful menstruation could have uterine contracting properties, we recorded whether these species were also used to ease birth, induce menstruation, abortion or expel the afterbirth, as these suggest spasmogenic activities. MATERIALS AND METHODS: We reviewed the literature documenting traditional plant use in the study area for dysmenorrhea, regulating or inducing menstruation, uterine cleansing, uterine fibroids, expelling the placenta and lochia and for easing childbirth. Thirty genera (59 species) used in at least two continents or frequently throughout one continent, where shortlisted from the 90 most salient plant species emerging from our literature review. Using Medline, we searched for pharmacological properties and/or mechanisms of action relevant to their traditional uses of the shortlisted species. We searched VigiBase™, the WHO global individual case safety report database, on reported adverse drug reactions associated with these species. RESULTS: More than 2000 plant species are used for menstrual disorders in the study area. The most salient uses are to treat painful menstruation, induce or regulate menses, and induce abortion. Around half (29) of the 59 most salient species have been tested for their pharmacological effects, of which 48% act as uterine spasmolytics and 31% as uterine spasmogenics. Several frequently used species contain toxic constituents, which may put women and their unborn children at serious risk. VigiBase(TM) listed adverse drug reactions for 18 of these species, but few reports came from the study area. CONCLUSIONS: Research into the risks and benefits of medicinal plants for menstrual complaints should be given a higher priority in reproductive health programs that respect traditional knowledge and practices. Increased data collection is needed on adverse drug reactions among women using herbal medicines for reproductive health, especially in countries with limited reproductive health facilities.

Ethnomedicine of menstruation in rural Dominica, West Indies.

ETHNOPHARMACOLOGICAL RELEVANCE: In Dominica, women offer dysmenorrhea, delayed menses, and menorrhagia as prevalent menstrual troubles. Dominican humoral theory considers menstruation to be "hot" such that menstrual problems are caused by the introduction of too much "cold" in the body. These conditions can be painful and may require herbal medicine. Our method finds the most culturally salient plants for these conditions-those which are of common knowledge across the population. We hypothesize that cultural agreement on ethnobotanical treatments (1) reflects their perceived ethnophysiological efficacy, and that (2) salient plants contain bioactive compounds appropriate for the menstrual conditions for which Dominicans employ the plants. MATERIALS AND METHODS: Qualitative data on local explanatory models and treatment of menstrual conditions were collected using participant-observation, focus groups, and informal key informant interviews. Quantitative ethnobotanical data come from freelist (or "free-list") tasks, conducted with 54 adults. RESULTS: Mean salience values calculated from freelisted data reveal that the same four plants, Cinnamomum verum (synonym Cinnamomum zeylanicum) (Lauraceae), Mentha suaveolens (Lamiaceae), Pimenta racemosa (Myrtaceae) and Sphagneticola trilobata (synonym Wedelia trilobata) (Asteraceae) are used to treat dysmenorrhea and delayed menses. The only remedy reported for menorrhagia, Sphagneticola trilobata (Asteraceae), is also a treatment for dysmenorrhea and delayed menses. The Dominican humoral system views menstruation as a "hot" condition, yet these "bush medicines" are also "hot." Dominicans do not view menstruation as a problem, rather, they reckon that excess "cold" in a woman׳s menstruating body impedes menstrual function to cause problems thus requiring "hot" plants to alleviate their symptoms. A literature review revealed that all four plants contain analgesic, anti-nociceptive, and anti-inflammatory properties. Additionally, Mentha suaveolens is muscle-relaxing and anti-spasmodic, Cinnamomum verum has a mild anti-coagulant, and Sphagneticola trilobata has wound healing, anti-stress, and sedative properties. CONCLUSIONS: In Dominican menstrual problems there is correspondence between cultural consensus, bioactivity, and humoral theory. Examining the ethnophysiology of menstruation and its complications provides evidence for the expectations of actions and effectiveness of locally culturally salient medicinal plants.

Gonadotrophin receptor hormone analogues in combination with add-back therapy: an update.

Gonadotrophin receptor hormone analogues (GnRHa) have been used in a range of sex hormone-dependent disorders. In the management of premenstrual syndrome, they can completely abolish symptoms. The success of GnRHa in the treatment of endometriosis and adjuvant therapy in the management of fibroids is proven. This efficacy does not come without a cost and the side-effects of the hypo-estrogenic state have limited their application. The use of add-back therapy to counter these effects has enabled wider application, longer durations of treatment and an increase in compliance. This review article is an update on the evidence supporting gonadotrophin receptor hormone analogues in combination with add-back therapy.

Effect of vitamin D3 treatment on glucose metabolism and menstrual frequency in polycystic ovary syndrome women: a pilot study.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances, in particular from insulin resistance. Accumulating evidence suggests that vitamin D deficiency may contribute to the development of insulin resistance. Hence, we aimed to examine the effect of vitamin D supplementation on metabolic and endocrine parameters in PCOS women. METHODS: Fifty-seven PCOS women were included in the study. PCOS women received 20,000 IU cholecalciferol weekly for 24 weeks. Anthropometric measures, oral glucose tolerance test, and blood analyses of endocrine parameters were performed at baseline and after 12 weeks (V2) and 24 weeks (V3). RESULTS: Forty-six PCOS women finished the study. 25-hydroxyvitamin D [25(OH)D] levels significantly increased from 28.0±11.0 ng/ml at baseline to 51.3±17.3 and 52.4±21.5 at V2 and V3, respectively (p<0.001). We observed a significant decrease of fasting and stimulated glucose (V3, p<0.05) and C-peptide levels (V2 and 3, p<0.001) after vitamin D treatment. Moreover, triglyceride and estradiol levels significantly decreased at V3 (p=0.001) and V2 (p=0.022), respectively, whereas total cholesterol (V2, p=0.008) and LDL cholesterol levels (V2, p=0.005; V3, p=0.026) significantly increased after vitamin D treatment. There were no changes in androgens. At V2, 14 out of 46 PCOS women previously affected by menstrual disturbances (30.4%) reported improvement of menstrual frequency; at V3, 23 out of 46 women (50.0%), who were oligo- or amenorrheic at baseline reported improvement. DISCUSSION: Our results suggest that vitamin D treatment might improve glucose metabolism and menstrual frequency in PCOS women. Further randomized controlled trails are warranted to confirm our findings.

Psychological and neuroendocrinological effects of odor of saffron (Crocus sativus).

AIM: The purpose of this study was to clarify the effects of saffron odor on symptoms unique to women, such as premenstrual syndrome (PMS), dysmenorrhea (menstrual pain) and irregular menstruation. MATERIALS AND METHODS: Thirty-five women with a normal sense of smell were exposed to saffron odor for 20 min. Saliva samples were then collected to measure levels of cortisol (C), testosterone (T) and 17-ß estradiol (E) by enzyme immunoassay, and the State-Trait Anxiety Inventory (STAI) was administered as a psychological test. RESULTS: Saffron odor significantly decreased C levels after short-term stimulation (20 min) in both follicular and luteal phases. E level after exposure to saffron odor was increased in both the follicular- and luteal-phase groups. STAI score decreased in the follicular and luteal phases in the saffron group. CONCLUSIONS: The present findings support the existence of physiological and psychological effects of saffron odor in women. Our results indicate that saffron odor exert some effects in the treatment of PMS, dysmenorrhea and irregular menstruation. This is the first report to suggest that saffron odor may be effective in treating menstrual distress.

Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women.

OBJECTIVE: The aim of this study was to compare the effectiveness of myo-inositol (MYO) and metformin, in monotherapy or in association with recombinant follicle stimulating hormone (r-FSH), in the treatment of menstrual irregularities, chronic anovulation, and female infertility in patients with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: One hundred twenty patients were randomly treated with metformin 1500 mg/day orally (n = 60), or 4 g MYO plus 400 microg folic acid daily (n = 60), continuously. If no pregnancy occurred, r-FSH (37.5 units/day) was added to the treatment for a maximum of three attempts. RESULTS: Fifty percent of the patients who assumed metformin restored spontaneous ovulation, 18.3% of these obtained pregnancy. The remaining 42 patients were treated with metformin plus r-FSH. Pregnancy occurred in a total of 11 women (26.1%). The total pregnancy rate was 36.6%. Sixty-five percent of the patients treated with MYO plus folic acid restored spontaneous ovulation activity, 30% of these obtained pregnancy. The remaining 38 patients were treated with MYO, folic acid plus r-FSH. Pregnancy occurred in a total of 11 women (28.9%). The total pregnancy rate was 48.4%. CONCLUSIONS: Both metformin and MYO, can be considered as first line treatment for restoring normal menstrual cycles in most patients with PCOS, even if MYO treatment seems to be more effective than metformin.