Robotic-assisted hysterectomy for benign gynecologic disease in the United States: in-hospital use of opioid and non-opioid analgesics.

To compare the in-hospital opioid and non-opioid analgesic use among women who underwent robotic-assisted hysterectomy (RH) vs. open (OH), vaginal (VH), or laparoscopic hysterectomy (LH). Records of women in the United States who underwent hysterectomy for benign gynecologic disease were extracted from the Premier Healthcare Database (2013-2019). Propensity score methods were used to create three 1:1 matched cohorts stratified in inpatients [RH vs. OH (N = 16,821 pairs), RH vs. VH (N = 6149), RH vs. LH (N = 11,250)] and outpatients [RH vs. OH (N = 3139), RH vs. VH (N = 29,954), RH vs. LH (N = 85,040)]. Opioid doses were converted to morphine milligram equivalents (MME). Within matched cohorts, opioid and non-opioid analgesic use was compared. On the day of surgery, the percentage of patients who received opioids differed only for outpatients who underwent RH vs. LH or VH (maximum difference = 1%; p < 0.001). RH was associated with lower total doses of opioids in all matched cohorts (each p < 0.001), with the largest difference observed between RH and OH: median (IQR) of 47.5 (25.0-90.0) vs. 82.5 (36.0-137.0) MME among inpatients and 39.3 (19.5-66.0) vs. 60.0 (35.0-113.3) among outpatients. After the day of surgery, fewer inpatients who underwent RH received opioids vs. OH (78.7 vs. 87.5%; p < 0.001) or LH (78.6 vs. 80.6%; p < 0.001). The median MME was lower for RH (15.0; 7.5-33.5) versus OH (22.5; 15.0-55.0; p < 0.001). Minor differences were observed for non-opioid analgesics. RH was associated with lower in-hospital opioid use than OH, whereas the same magnitude of difference was not observed for RH vs. LH or VH.

Green Tea and Benign Gynecologic Disorders: A New Trick for An Old Beverage?

Green tea is harvested from the tea plant Camellia sinensis and is one of the most widely consumed beverages worldwide. It is richer in antioxidants than other forms of tea and has a uniquely high content of polyphenolic compounds known as catechins. Epigallocatechin-3-gallate (EGCG), the major green tea catechin, has been studied for its potential therapeutic role in many disease contexts, including pathologies of the female reproductive system. As both a prooxidant and antioxidant, EGCG can modulate many cellular pathways important to disease pathogenesis and thus has clinical benefits. This review provides a synopsis of the current knowledge on the beneficial effects of green tea in benign gynecological disorders. Green tea alleviates symptom severity in uterine fibroids and improves endometriosis through anti-fibrotic, anti-angiogenic, and pro-apoptotic mechanisms. Additionally, it can reduce uterine contractility and improve the generalized hyperalgesia associated with dysmenorrhea and adenomyosis. Although its role in infertility is controversial, EGCG can be used as a symptomatic treatment for menopause, where it decreases weight gain and osteoporosis, as well as for polycystic ovary syndrome (PCOS).

Inositols in the ovaries: activities and potential therapeutic applications.

INTRODUCTION: Myo-inositol (MI) and d-chiro-inositol (DCI) play a key role in ovarian physiology, as they are second messengers of insulin and gonadotropins. Ex-vivo and in-vitro experiments demonstrate that both isomers are deeply involved in steroid biosynthesis, and that reduced MI-to-DCI ratios are associated with pathological imbalance of sex hormones. AREAS COVERED: This expert opinion provides an overview of the physiological distribution of MI and DCI in the ovarian tissues, and a thorough insight of their involvement into ovarian steroidogenesis. Insulin resistance and compensatory hyperinsulinemia dramatically reduce the MI-to-DCI ratio in the ovaries, leading to gynecological disorders characterized by hyperandrogenism, altered menstrual cycle and infertility. EXPERT OPINION: Available evidence indicates that MI and DCI have very specific physiological roles and, seemingly, physiological MI-to-DCI ratios in the ovaries are crucial to maintain the correct homeostasis of steroids. Inositol treatments should be evaluated on the patients' specific conditions and needs, as long-term supplementation of high doses of DCI may cause detrimental effects on the ovarian functionality. In addition, the effects of inositol therapy on the different PCOS phenotypes should be further investigated in order to better tailor the supplementation.

Phytoprogestins: Unexplored Food Compounds with Potential Preventive and Therapeutic Effects in Female Diseases.

In recent years, there has been an increasing interest in natural therapies to prevent or treat female diseases. In particular, many studies have focused on searching natural compounds with less side effects than standard hormonal therapies. While phytoestrogen-based therapies have been extensively studied, treatments with phytoprogestins reported in the literature are very rare. In this review, we focused on compounds of natural origin, which have progestin effects and that could be good candidates for preventing and treating female diseases. We identified the following phytoprogestins: kaempferol, apigenin, luteolin, and naringenin. In vitro studies showed promising results such as the antitumoral effects of kaempferol, apigenin and luteolin, and the anti-fibrotic effects of naringenin. Although limited data are available, it seems that phytoprogestins could be a promising tool for preventing and treating hormone-dependent diseases.

Alien woody plants are more versatile than native, but both share similar therapeutic redundancy in South Africa.

Understanding why alien plant species are incorporated into the medicinal flora in several local communities is central to invasion biology and ethnobiology. Theories suggest that alien plants are incorporated in local pharmacopoeias because they are more versatile or contribute unique secondary chemistry which make them less therapeutically redundant, or simply because they are locally more abundant than native species. However, a lack of a comprehensive test of these hypotheses limits our understanding of the dynamics of plants knowledge, use and potential implications for invasion. Here, we tested the predictions of several of these hypotheses using a unique dataset on the woody medicinal flora of southern Africa. We found that the size of a plant family predicts the number of medicinal plants in that family, a support for the non-random hypothesis of medicinal plant selection. However, we found no support for the diversification hypothesis: i) both alien and native plants were used in the treatment of similar diseases; ii) significantly more native species than alien contribute to disease treatments particularly of parasitic infections and obstetric-gynecological diseases, and iii) alien and native species share similar therapeutic redundancy. However, we found support for the versatility hypothesis, i.e., alien plants were more versatile than natives. These findings imply that, although alien plant species are not therapeutically unique, they do provide more uses than native plants (versatility), thus suggesting that they may not have been introduced primarily for therapeutic reasons. We call for similar studies to be carried out on alien herbaceous plants for a broader understanding of the integration of alien plants into the pharmacopoeias of the receiving communities.

Selective Progesterone Receptor Modulators (SPRMs) and Androgen Receptor Modulators (SARMs) as Treatment for Benign Gynecologic Diseases.

Common benign gynecologic conditions such as uterine fibroids and endometriosis are linked to chronic pelvic pain, abnormal and heavy uterine bleeding, and infertility. Effective medical management of these diseases is an unmet need. The steroid hormones progesterone (P4), estrogen (E2), and testosterone play a major role in reproductive physiology and uterine pathologies. Notably, selective progesterone receptor modulators have shown considerable promise as treatment options for some hormone-dependent conditions. More limited data are available regarding the safety and efficacy of selective androgen receptor modulators. In this report we review current evidence for selective progesterone receptor modulators and selective androgen receptor modulators as treatment options for benign gynecologic conditions.

Drug delivery strategies for management of women's health issues in the upper genital tract.

The female upper genital tract (UGT) hosts important reproductive organs including the cervix, uterus, fallopian tubes, and ovaries. Several pathologies affect these organ systems such as infections, reproductive issues, structural abnormalities, cancer, and inflammatory diseases that could have significant impact on women's overall health. Effective disease management is constrained by the multifaceted nature of the UGT, complex anatomy and a dynamic physiological environment. Development of drug delivery strategies that can overcome mucosal and safety barriers are needed for effective disease management. This review introduces the anatomy, physiology, and mucosal properties of the UGT and describes drug delivery barriers, advances in drug delivery technologies, and opportunities available for new technologies that target the UGT.

The Role of microRNA Let-7d in Female Malignancies and Diseases of the Female Reproductive Tract.

microRNAs are small noncoding RNAs that regulate gene expression at the posttranscriptional level. Let-7d is a microRNA of the conserved let-7 family that is dysregulated in female malignancies including breast cancer, ovarian cancer, endometrial cancer, and cervical cancer. Moreover, a dysregulation is observed in endometriosis and pregnancy-associated diseases such as preeclampsia and fetal growth restriction. Let-7d expression is regulated by cytokines and steroids, involving transcriptional regulation by OCT4, MYC and p53, as well as posttranscriptional regulation via LIN28 and ADAR. By downregulating a wide range of relevant mRNA targets, let-7d affects cellular processes that drive disease progression such as cell proliferation, apoptosis (resistance), angiogenesis and immune cell function. In an oncological context, let-7d has a tumor-suppressive function, although some of its functions are context-dependent. Notably, its expression is associated with improved therapeutic responses to chemotherapy in breast and ovarian cancer. Studies in mouse models have furthermore revealed important roles in uterine development and function, with implications for obstetric diseases. Apart from a possible utility as a diagnostic blood-based biomarker, pharmacological modulation of let-7d emerges as a promising therapeutic concept in a variety of female disease conditions.

Pharmacokinetic study of traditional Japanese Kampo medicine shimotsuto used to treat gynecological diseases in rats.

Shimotsuto is a traditional Japanese Kampo medicine used to treat gynecological diseases, such as irregular menstruation, in addition to oversensitivity to cold and chilblains. Part of the pharmacological actions of shimotsuto is traditionally considered to be exerted by an improvement effect of the blood and the circulatory system. Multiple ingredients (e.g., catalpol and paeoniflorin) contained in shimotsuto have been reported to have pharmacological activities on the blood and circulatory system, and thus been considered to contribute to the pharmacological actions of shimotsuto. However, it remains unclear whether the ingredients can be absorbed into the body following oral administration of shimotsuto. The aim in the present study was to specify shimotsuto ingredient absorbed into the systemic circulation in rats. Seven candidate active ingredients (catalpol, paeoniflorin, albiflorin, ligustilide, senkyunolide A, butylphthalide, and ferulic acid) in plasma after oral administration of shimotsuto were quantified by targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. This study also performed nontargeted LC-MS/MS analysis of plasma following administration of constituent crude drugs of shimotsuto to find extensively blood-absorbed ingredients of shimotsuto. Among detected peaks in the nontargeted analysis, two peaks could be identified as bergapten and 8-debenzoylpaeoniflorin, subsequently their concentrations in shimotsuto-treated rat plasma were quantified. These pharmacokinetic studies indicated that catalpol showed the highest plasma concentration following administration of shimotsuto, followed by 8-debenzoylpaeoniflorin. This study suggests that all nine ingredients are absorbed into the blood following oral administration of shimotsuto and possibly contribute to its pharmacological action.

Azithromycin in the treatment of rectogenital Chlamydia trachomatis infections: end of an era?

INTRODUCTION: Azithromycin was recommended as the first-line therapeutic regimen for treatment of genital infections in men and women by the Centers for Disease Control in 1998. A series of studies of azithromycin for treatment of rectal chlamydial infection in men who have sex with men (MSM) found that azithromycin was significantly less effective than doxycycline. AREAS COVERED: Literature on treatment of rectal C. trachomatis from 2000 through May 2020 was searched using PubMed. Retrospective and observational studies were identified documenting the frequency and treatment of rectal chlamydial infection in MSM, heterosexual men and women that reported lower efficacy of single-dose azithromycin compared to doxycycline. Literature on possible reasons for the lower efficacy were also reviewed including studies of antibiotic resistance, impact of organism load, and persistent infection in rectal specimens and pharmacokinetics and pharmacodynamics of azithromycin in rectal tissue. EXPERT OPINION: The available data suggests that single-dose azithromycin is not as effective as azithromycin for the treatment of rectal infection in MSM and women. Most of these data have been retrospective or from observational studies. Final recommendations will depend on the outcome of prospective, randomized, treatment studies. We may also need to examine other dosage regimens for azithromycin.

Integration of prevention and control measures for female genital schistosomiasis, HIV and cervical cancer.

Female genital schistosomiasis as a result of chronic infection with Schistosoma haematobium (commonly known as bilharzia) continues to be largely ignored by national and global health policy-makers. International attention for large-scale action against the disease focuses on whether it is a risk factor for the transmission of human immunodeficiency virus (HIV). Yet female genital schistosomiasis itself is linked to pain, bleeding and sub- or infertility, leading to social stigma, and is a common issue for women in schistosomiasis-endemic areas in sub-Saharan Africa. The disease should therefore be recognized as another component of a comprehensive health and human rights agenda for women and girls in Africa, alongside HIV and cervical cancer. Each of these three diseases has a targeted and proven preventive intervention: antiretroviral therapy and pre-exposure prophylaxis for HIV; human papilloma virus vaccine for cervical cancer; and praziquantel treatment for female genital schistosomiasis. We discuss how female genital schistosomiasis control can be integrated with HIV and cervical cancer care. Such a programme will be part of a broader framework of sexual and reproductive health and rights, women's empowerment and social justice in Africa. Integrated approaches that join up multiple public health programmes have the potential to expand or create opportunities to reach more girls and women throughout their life course. We outline a pragmatic operational research agenda that has the potential to optimize joint implementation of a package of measures responding to the specific needs of girls and women.

La schistosomiase génitale féminine, résultant d'une infection chronique à Schistosoma haematobium (également connue sous le nom de bilharziose), continue d'être largement ignorée par les responsables des politiques de santé nationales et internationales. Si le monde lui accorde son attention en vue de mener une action à grande échelle contre la maladie, c'est surtout pour déterminer s'il s'agit d'un facteur de risque pour la transmission du virus de l'immunodéficience humaine (VIH). Pourtant, la schistosomiase génitale féminine est associée à des douleurs, des saignements et peut engendrer l'hypofertilité, voire la stérilité. Par conséquent, celles qui en souffrent sont souvent stigmatisées, et le problème est courant dans les régions endémiques d'Afrique subsaharienne. Cette maladie doit donc être considérée comme composante à part entière d'une approche globale de la santé et des droits humains pour les femmes et filles africaines, à l'instar du VIH et du cancer du col de l'utérus. Chacune de ces trois maladies fait l'objet d'une intervention préventive ciblée qui a déjà fait ses preuves: le traitement antirétroviral et la prophylaxie pré-exposition pour le VIH; le vaccin contre le papillomavirus humain pour le cancer du col de l'utérus; et l'administration de praziquantel pour la schistosomiase génitale féminine. Le présent document se penche sur la manière d'intégrer la schistosomiase génitale féminine dans la prise en charge du VIH et du cancer du col de l'utérus. Un tel programme fera partie d'un cadre plus vaste consacré aux droits et à la santé sexuelle et reproductive, à l'émancipation des femmes et à la justice sociale en Afrique. Les approches intégrées qui regroupent plusieurs programmes de santé publique permettent d'élargir des perspectives ou de créer des opportunités visant à atteindre un plus grand nombre de filles et de femmes tout au long de leur vie. Nous exposons les grandes lignes d'un programme de recherches pragmatiques et opérationnelles capable d'optimiser la mise en œuvre conjointe d'une série de mesures qui répondent aux besoins spécifiques des filles et des femmes.

Los responsables de formular las políticas sanitarias nacionales y globales siguen ignorando en gran medida la esquistosomiasis genital femenina como consecuencia de la infección crónica por Schistosoma haematobium (conocida comúnmente como bilharziasis). La atención internacional para adoptar medidas de gran alcance contra la enfermedad se centra en determinar si es un factor de riesgo para la transmisión del virus de la inmunodeficiencia humana (VIH). Sin embargo, la propia esquistosomiasis genital femenina está vinculada al dolor, las hemorragias y la infertilidad o subfertilidad, lo que conduce al estigma social, además de ser un problema común para las mujeres de las áreas en donde la esquistosomiasis es endémica en el África subsahariana. Por consiguiente, la enfermedad debe ser reconocida como otro componente de un programa integral de salud y de derechos humanos para las mujeres y las niñas de África, junto con el VIH y el cáncer de cuello uterino. Cada una de estas tres enfermedades tiene una intervención preventiva específica y comprobada: la terapia antirretroviral y la profilaxis previa a la exposición para el VIH; la vacuna contra el virus del papiloma humano para el cáncer de cuello uterino; y el tratamiento con praziquantel para la esquistosomiasis genital femenina. Se analiza cómo el control de la esquistosomiasis genital femenina se puede integrar con la atención del VIH y el cáncer de cuello uterino. Ese programa formará parte de un marco más amplio de salud y de derechos sexuales y reproductivos, de empoderamiento de la mujer y de justicia social en África. Los enfoques integrados que unen múltiples programas de salud pública tienen el potencial de ampliar o crear oportunidades para llegar a más niñas y mujeres a lo largo de sus vidas. Se describe a grandes rasgos un programa de investigación operacional pragmático que tiene el potencial de optimizar la implementación conjunta de una serie de medidas que respondan a las necesidades específicas de las niñas y de las mujeres.

A Case Report of Pelvic Actinomycosis and a Literature Review.

BACKGROUND The aim of this study was to report the clinical diagnosis and treatment of a case of pelvic actinomycosis in our hospital and provide a review of recent literature. CASE REPORT The patient was a 54-year-old woman who was admitted to our hospital due to "bilateral lower abdominal tenderness accompanied with anorexia and vomiting for 3 months". After admission, a variety of imaging examinations found pelvic space-occupying lesions, which were considered as malignant. She underwent surgery and pelvic actinomycosis was diagnosed by postoperative pathology. Postoperatively, she was treated with a high-dose sufficient course of penicillin (20 million U, iv gtt) for 14 days and she is currently under close follow-up for 1 year, with no recurrent symptoms. CONCLUSIONS Pelvic actinomycosis is rare and often forms mass invasion into the tissue structure around the pelvic cavity, which is easily misdiagnosed as ovarian malignant tumor. The criterion standard for diagnosing an infection is culture, with histopathology aiding the diagnosis.

An Assay on the Possible Effect of Essential Oil Constituents on Receptors Involved in Women's Hormonal Health and Reproductive System Diseases.

Aromatic herbal remedies, hydrosols, and essential oils are widely used for women's hormonal health. Scientific investigation of their major constituents may prevent unwanted infertility cases, fetal abnormalities, and drug-herb interactions. It also may lead to development of new medications. A list of 265 volatile molecules (mainly monoterpenes and sesquiterpenes) were prepared from a literature survey in Scopus and PubMed (2000-2019) on hydrosols and essential oils that are used for women's hormonal and reproductive health conditions. The PDB (protein data bank) files of the receptors (136 native PDB files) that involve with oxytocin, progesterone, estrogen, prolactin, acetyl choline, androgen, dopamine, human chorionic gonadotropin, luteinizing hormone, follicle-stimulating hormone, aromatase, and HER2 receptors were downloaded from Protein Data Bank. An in silico study using AutoDock 4.2 and Vina in parallel mode was performed to investigate possible interactions of the ligands with the receptors. Drug likeliness was investigated for the most active molecules using DruLiTo software. Aristola-1(10),8-diene, bergapten (5-methoxypsoralen), α-bergamotene, bicyclogermacrene, α-bisabolol oxide A, α-bisabolone oxide, p-cymen-8-ol, 10-epi elemol, α-elemol, ß-eudesmol, 7-epi-ß-eudesmol, ficusin, ß-humulene, methyl jasmonate, nerolidol, pinocarvone, (+)-spathulenol, and thujone had better interactions with some androgen, aromatase, estrogen, progesterone, HER2, AChR, and/or dopamine receptors. Most of these molecules had an acceptable drug likeliness except for α-bergamotene, bicyclogermacrene, ß-humulene, and aristola-1(10),8-diene. Some volatile natural molecules can be considered as lead compound for drug development to treat hormonal conditions.

Extrapulmonary Surfactant Therapy: Review of Available Data and Research/Development Issues.

Since the discovery of surfactant, a large amount of knowledge has been accumulated about its biology and pharmacology. Surfactant is the cornerstone of neonatal respiratory critical care, but its proteins and phospholipids are produced in various tissues and organs, with possible roles only partially similar to that played in the alveoli. As surfactant research is focused mainly on its respiratory applications, knowledge about the possible role of surfactant in extrapulmonary disorders has never been summarized. Here we aim to comprehensively review the data about surfactant biology and pharmacology in organs other than the lung, especially focusing in the more promising surfactant extrapulmonary roles. We also review any preclinical or clinical data available about the therapeutic use of surfactant in these contexts. We offer a summary of knowledge and research/development milestones, as possible useful guidance for researchers of multidisciplinary background.

90 YEARS OF PROGESTERONE: Selective progesterone receptor modulators in gynaecological therapies.

Abnormal uterine bleeding (AUB) is a chronic, debilitating and common condition affecting one in four women of reproductive age. Current treatments (conservative, medical and surgical) may be unsuitable, poorly tolerated or may result in loss of fertility. Selective progesterone receptor modulators (SPRMs) influence progesterone-regulated pathways, a hormone critical to female reproductive health and disease; therefore, SPRMs hold great potential in fulfilling an unmet need in managing gynaecological disorders. SPRMs in current clinical use include RU486 (mifepristone), which is licensed for pregnancy interruption, and CDB-2914 (ulipristal acetate), licensed for managing AUB in women with leiomyomas and in a higher dose as an emergency contraceptive. In this article, we explore the clinical journey of SPRMs and the need for further interrogation of this class of drugs with the ultimate goal of improving women's quality of life.

New clinical targets of d-chiro-inositol: rationale and potential applications.

INTRODUCTION: Inositols have a key role in ovarian physiology and the literature reports a wealth of studies about the major isomer, myo-inositol (MI). However, information about d-chiro-inositol (DCI) is still scarce, despite the ratio MI:DCI is tissue-specific and actively maintained by an insulin-dependent epimerase enzyme. AREAS COVERED: This expert opinion provides an overview of the physiological contribution of DCI in regulating steroidogenesis. DCI indeed mediates the intracellular signaling of insulin, which induces the biosynthesis of androgens. Studies on second messengers of insulin also revealed that DCI has a specific role in modulating the activity of aromatase enzyme. Specifically, recent findings demonstrated that DCI influences the enzyme gene expression, thus reducing the conversion of androgens into estrogens. EXPERT OPINION: Available evidence suggests that the effects of DCI administration may be similar to those of aromatase inhibitors, but without causing hypo-estrogenic states. Therefore, DCI treatments should be evaluated for either estrogen-dependent gynecological conditions or low testosterone states in male subjects.

Ingenol Mebutate Gel 0.05% in the Treatment of Anogenital Warts: A Prospective Controlled Trial Comparing It With Topical Podophyllin Solution 25.

BACKGROUND: Anogenital warts (AGWs) are a common therapeutic challenge. All therapies are associated with burning, pain, and frustrating high rate of recurrence. The search for a new alternative continues. Recently, a diterpene ester extracted from the Euphorbia peplus plant (ingenol mebutate [IM]) has been shown to possess activity against AGWs. OBJECTIVE: This study aimed to compare and evaluate the therapeutic efficacy and safety of topical 0.05% ingenol gel with another herbal extract medication (topical 25% podophyllin solution) in treatment of AGWs. METHODS: This was a comparative single blinded nonrandomized, 2-arm trial of ingenol 0.05% gel versus podophyllin solution 25% administered up to 6 times to patients with AGWs. To evaluate the therapeutic efficacy, the complete clearance rate and recurrence rate were assessed 1 and 12 weeks after last treatment, respectively. Safety was assessed by occurrence and severity of pain and local skin reaction (LSR). RESULTS: Of 31 and 36 patients in the IM group and podophyllin group who completed the study, initial complete resolution was observed in 20 (64.5%) and 14 (38.9%) patients, respectively (P = 0.03). The initial clearance was faster in the IM group (2.00 ± 0.91 weeks) compared with the podophyllin group (4.21 ± 1.05 weeks, P = 0.00). After 3 months, recurrence was seen in 13 (65.0%) of 20 patients in the IM group and 6 (42.8%) of 14 in the podophyllin group (P = 0.20). The number of patients with complete resolution after 3 months was not different between the 2 groups (7/31 in the IM group and 8/36 in the podophyllin group, P = 0.97). The mean ± SD severity scores for LSR and pain in the IM group were 6.65 ± 1.76 and 6.13 ± 2.57, respectively, which was significantly higher than their scores (3.39 ± 1.57 and 2.58 ± 1.38) in the podophyllin group (P = 0.00). CONCLUSION: Ingenol mebutate 0.05% gel is effective as podophyllin 25% solution in treating AGWs, with further benefit of being much more rapid. However, high recurrence rate, sever pain, and LSR limit its use.