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Pharmaceuticals
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Current Therapies for Endometriosis, Adenomyosis and Endometrial Cancer
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Current Therapies for Endometriosis, Adenomyosis and Endometrial Cancer

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (24 February 2025) | Viewed by 31807

Special Issue Editors

Dr. Ambrogio Pietro Londero

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Guest Editor
Research Associate in the Academic Unit of Obstetrics and Gynaecology, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Infant Health, University of Genoa, Genova, Italy
Interests: endometrial cancer
Special Issues, Collections and Topics in MDPI journals
Dr. Anjeza Xholli

E-Mail Website
Guest Editor
Academic Unit of Obstetrics and Gynecology, Maternal and Child Health (DiNOGMI), IRCCS Ospedale Policlinico San Martino, Genova, Italy
Interests: gynecological ultrasound; endometriosis and pelvic pain; oncological gynecology
Dr. Angelo Cagnacci

E-Mail Website
Guest Editor
Clinic of Obstetrics and Gynecology, Azienda Ospedaliera Universitaria San Martino di Genova, Genova, Italy
Interests: menopause; contraception; endometriosis; pelvic pain; gynecological endocrinology; biological rhytms; gynecological oncology

Special Issue Information

Dear Colleagues,

Endometriosis, adenomyosis, and endometrial cancer are three gynecological conditions with varying options for treatment. Endometriosis constitutes a complex disease whose etiology is not fully understood. Reflecting this, therapies to address this condition are mainly symptomatic, aimed at pain control and improving fertility through medical treatments, surgery, and medically assisted procreation. Adenomyosis is another estrogen-dependent condition that can cause pain, heavy bleeding, and infertility. While drug therapies can effectively relieve symptoms, the respite is temporary. Adenomyosis can also be associated with other conditions like endometriosis, and in rare cases, it can lead to adenocarcinomas, making diagnosis and treatment complicated. Conversely, there have been promising developments in identifying novel diagnostic markers and therapeutic targets of endometrial cancer. Potential therapeutic strategies for endometrial cancer include targeting specific pathways, such as mTOR or CDK4/6, and analyzing long non-coding RNA. Radiomics features and models have also been validated to differentiate endometrial cancer risk groups. However, a better understanding of these conditions' mechanisms is still needed to develop therapies with curative or preventive application. New developments for the treatment all three of the discussed pathologies include both hormonal and non-hormonal treatments. This Special Volume aims to discuss the merits of this area's current and future therapeutic lines.

Dr. Ambrogio Pietro Londero
Dr. Anjeza Xholli
Dr. Angelo Cagnacci
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • endometriosis
  • adenomyosis
  • endometrial cancer
  • hormonal therapy
  • non-hormonal therapy
  • pain management
  • fertility preservation
  • complementary/alternative medicine
  • radiation therapy
  • chemotherapy
  • immunotherapy

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Published Papers (7 papers)

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Research

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18 pages, 7657 KiB  
Article
Optimization and Evaluation of Cannabis-Based Magistral Formulations: A Path to Personalized Therapy
by Bożena Grimling, Magdalena Fast, Magdalena Okoniewska, Artur Owczarek and Bożena Karolewicz
Pharmaceuticals 2025, 18(1), 73; https://doi.org/10.3390/ph18010073 - 9 Jan 2025
Viewed by 1397
Abstract
Introduction: The official implementation of pharmaceutical-grade cannabis raw materials for medicinal use has permitted doctors to prescribe and pharmacists to prepare cannabis-based formulations. The objective of the pharmaceutical development and manufacturing process optimization work was to propose a suppository formulation containing doses of [...] Read more.
Introduction: The official implementation of pharmaceutical-grade cannabis raw materials for medicinal use has permitted doctors to prescribe and pharmacists to prepare cannabis-based formulations. The objective of the pharmaceutical development and manufacturing process optimization work was to propose a suppository formulation containing doses of 25 mg and 50 mg of tetra-hydrocannabinol (∆-9-THC) as an alternative to existing inhalable or orally administered formulations. The formulation could be used for rectal or vaginal administration, thereby providing dosage control in the treatment of endometriosis and other conditions involving pain. In this study, two substrates from suppositories with standardized Cannabis extractum normatum (CEX) were used: cocoa butter and Witepsol® H15. Materials and Methods: The long-term stability of CEX was investigated over a period of up to 24 months. The concentrations of ∆-9-THC, cannabidiol (CBD), and cannabinol (CBN) were determined using an HPLC method. Furthermore, the water content of the extract, the ethanol residue, and the microbiological purity were determined. The pharmaceutical properties of CEX-incorporated suppositories, namely content uniformity, hardness, softening time, total deformation time, disintegration time, and the release profile of ∆-9-THC, CBD, and CBN, were evaluated in order to develop optimal preparation procedures for pharmacists. Results and Discussion: Following a 24-month stability study on CEX, no significant alterations in component content were observed beyond the specified requirements. The disintegration time, total deformation time, and hardness of the suppositories based on Witepsol® H15 with CEX were found to be longer and higher, respectively, than those of suppositories formulated with cocoa butter. In vitro studies demonstrated that suppositories prepared with Witepsol® H15 exhibited superior release of ∆-9-THC compared to those prepared with cocoa butter. Conclusions: We suggest that pharmacists making prescription drugs in a pharmacy setting in the form of medical marijuana suppositories will receive a better release profile of the drug by choosing Witepsol® H15 as a substrate. Full article
(This article belongs to the Special Issue Current Therapies for Endometriosis, Adenomyosis and Endometrial Cancer)
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Review

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17 pages, 1939 KiB  
Review
Exosomes in Ovarian Cancer: Towards Precision Oncology
by Maria Grazia Perrone, Silvana Filieri, Amalia Azzariti, Domenico Armenise, Olga Maria Baldelli, Anselma Liturri, Anna Maria Sardanelli, Savina Ferorelli, Morena Miciaccia and Antonio Scilimati
Pharmaceuticals 2025, 18(3), 371; https://doi.org/10.3390/ph18030371 - 5 Mar 2025
Cited by 1 | Viewed by 850
Abstract
Background: Identification of targetable biomarkers to improve early disease detection and overall patient outcomes is becoming an urgent need in clinical oncology. Ovarian cancer (OC) has one of the highest mortality rates among gynecological cancers. It is asymptomatic and almost always diagnosed [...] Read more.
Background: Identification of targetable biomarkers to improve early disease detection and overall patient outcomes is becoming an urgent need in clinical oncology. Ovarian cancer (OC) has one of the highest mortality rates among gynecological cancers. It is asymptomatic and almost always diagnosed at an advanced stage (III or IV), leading to a 5-year survival rate of approximately 35%. Methods: Current therapeutic approaches for OC are very limited and mainly consist of cytoreductive surgery and cisplatin plus taxane-based chemotherapy. No gender and tumor specific biomarkers are known. Exosomes, lipid bilayer vesicles of endocytic origin secreted by most cell types, represent sources of information for their involvement in the onset and progression of many diseases. Hence, research on exosome contents as tools and targets in precise oncology therapy provides knowledge essential to improving diagnosis and prognosis of the disease. Results: This review attempts to give an overview of how exosomes are implicated in ovarian carcinoma pathogenesis to trigger further cancer exosome-based investigations aimed at developing ovarian cancer fine-tuning diagnostic methodologies. Conclusions: It is essential to investigate exosome-based cancer drugs to advance understanding, improve treatment plans, create personalized strategies, ensure safety, and speed up clinical translation to increase patients’ overall survival and quality of life. Papers published in PubMed and Web of Science databases in the last five years (2020–2024) were used as a bibliographic source. Full article
(This article belongs to the Special Issue Current Therapies for Endometriosis, Adenomyosis and Endometrial Cancer)
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15 pages, 586 KiB  
Review
Endometriosis: Molecular Pathophysiology and Recent Treatment Strategies—Comprehensive Literature Review
by Marcin Sadłocha, Jakub Toczek, Katarzyna Major, Jakub Staniczek and Rafał Stojko
Pharmaceuticals 2024, 17(7), 827; https://doi.org/10.3390/ph17070827 - 24 Jun 2024
Cited by 3 | Viewed by 4944
Abstract
Endometriosis is an enigmatic disease, with no specific cause or trigger yet discovered. Major factors that may contribute to endometriosis in the pelvic region include environmental, epigenetic, and inflammatory factors. Most experts believe that the primary mechanism behind the formation of endometrial lesions [...] Read more.
Endometriosis is an enigmatic disease, with no specific cause or trigger yet discovered. Major factors that may contribute to endometriosis in the pelvic region include environmental, epigenetic, and inflammatory factors. Most experts believe that the primary mechanism behind the formation of endometrial lesions is associated with Sampson’s theory of “retrograde menstruation”. This theory suggests that endometrial cells flow backward into the peritoneal cavity, leading to the development of endometrial lesions. Since this specific mechanism is also observed in healthy women, additional factors may be associated with the formation of endometrial lesions. Current treatment options primarily consist of medical or surgical therapies. To date, none of the available medical therapies have proven effective in curing the disorder, and symptoms tend to recur once medications are discontinued. Therefore, there is a need to explore and develop novel biomedical targets aimed at the cellular and molecular mechanisms responsible for endometriosis growth. This article discusses a recent molecular pathophysiology associated with the formation and progression of endometriosis. Furthermore, the article summarizes the most current medications and surgical strategies currently under investigation for the treatment of endometriosis. Full article
(This article belongs to the Special Issue Current Therapies for Endometriosis, Adenomyosis and Endometrial Cancer)
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19 pages, 2189 KiB  
Review
Gut Microbiota and Endometriosis: Exploring the Relationship and Therapeutic Implications
by Anjeza Xholli, Francesca Cremonini, Isabella Perugi, Ambrogio Pietro Londero and Angelo Cagnacci
Pharmaceuticals 2023, 16(12), 1696; https://doi.org/10.3390/ph16121696 - 7 Dec 2023
Cited by 7 | Viewed by 8685
Abstract
Endometriosis is a common inflammatory disease affecting women of reproductive age, characterized by the growth of endometrial tissue beyond the uterus. In addition to gynecological manifestations, many endometriosis patients experience gastrointestinal symptoms, indicating a potential association between gut health and the disease. Recent [...] Read more.
Endometriosis is a common inflammatory disease affecting women of reproductive age, characterized by the growth of endometrial tissue beyond the uterus. In addition to gynecological manifestations, many endometriosis patients experience gastrointestinal symptoms, indicating a potential association between gut health and the disease. Recent studies have revealed alterations in the gut microbiota of individuals with endometriosis, including reduced diversity, microbial composition imbalances, and pathogenic bacteria. These changes can disrupt immune function, increase inflammation, and contribute to the chronic inflammatory state observed in endometriosis. Moreover, dysregulation of intestinal permeability may further exacerbate gastrointestinal symptoms in affected individuals. Understanding the role of the gut microbiota and intestinal permeability in endometriosis can provide valuable insights into disease pathogenesis, aid in non-invasive diagnostic approaches, and open new avenues for therapeutic interventions. Probiotics, in particular, have shown promise in improving endometriosis-associated pain symptoms and reducing endometriotic lesions in animal models. This review suggests that additional research and well-designed clinical trials are necessary to validate the potential diagnostic and therapeutic benefits of manipulating the gut microbiota in managing endometriosis and its gastrointestinal symptoms, thereby improving the quality of life for those affected. Full article
(This article belongs to the Special Issue Current Therapies for Endometriosis, Adenomyosis and Endometrial Cancer)
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20 pages, 1527 KiB  
Review
Clinical Efficacy, Pharmacokinetics, and Safety of the Available Medical Options in the Treatment of Endometriosis-Related Pelvic Pain: A Scoping Review
by Mislav Mikuš, Marina Šprem Goldštajn, Antonio Simone Laganà, Franka Vukorepa and Mario Ćorić
Pharmaceuticals 2023, 16(9), 1315; https://doi.org/10.3390/ph16091315 - 18 Sep 2023
Cited by 6 | Viewed by 3659
Abstract
Background: In this scoping review, we sought to identify published studies evaluating the drugs currently used in the treatment of endometriosis-related pelvic pain, with reflection on their chemical properties, pharmacokinetics, safety profile, and clinical efficacy. Methods: A literature search was conducted with the [...] Read more.
Background: In this scoping review, we sought to identify published studies evaluating the drugs currently used in the treatment of endometriosis-related pelvic pain, with reflection on their chemical properties, pharmacokinetics, safety profile, and clinical efficacy. Methods: A literature search was conducted with the use of the PubMed and EMBASE electronic databases, focusing on identifying articles published in English between January 1990 and 2023. Results: Based on the included studies, current therapy options for the treatment of endometriosis-related pain identified and reviewed in this article were: (1) non-steroidal anti-inflammatory drugs; (2) combined oral contraceptive (COCs); (3) progestins; (4) gonadotropin-releasing hormone agonists and antagonists; (5) aromatase inhibitors (AIs); (6) selective estrogen and progesterone receptor modulators; and (7) levonorgestrel-intrauterine device. Conclusions: Based on the published evidence, clinicians should consider NSAIDs, COCs, and progestins as the first-line medical therapies. Compared with second-line options, such as GnRH agonists/antagonists or AIs, the abovementioned first-line options are well tolerated, efficacious, and exhibit lower overall price. Future research priorities should be to identify novel target therapies and to evaluate the effects of available drugs through different routes of administration. Full article
(This article belongs to the Special Issue Current Therapies for Endometriosis, Adenomyosis and Endometrial Cancer)
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Other

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10 pages, 447 KiB  
Perspective
Effects, Doses, and Applicability of Gestrinone in Estrogen-Dependent Conditions and Post-Menopausal Women
by Guilherme Renke, Mariana Antunes, Renato Sakata and Francisco Tostes
Pharmaceuticals 2024, 17(9), 1248; https://doi.org/10.3390/ph17091248 - 22 Sep 2024
Viewed by 6277
Abstract
Gestrinone (R-2323), or ethylnorgestrienone, is a synthetic steroid of the 19-nortestosterone group more commonly used as an oral, intravaginal, or subcutaneous implant for the treatment of endometriosis, contraception, and estrogen-dependent conditions such as hypermenorrhea, premenstrual dysphoria, and intense menstrual cramps. This review aims [...] Read more.
Gestrinone (R-2323), or ethylnorgestrienone, is a synthetic steroid of the 19-nortestosterone group more commonly used as an oral, intravaginal, or subcutaneous implant for the treatment of endometriosis, contraception, and estrogen-dependent conditions such as hypermenorrhea, premenstrual dysphoria, and intense menstrual cramps. This review aims to reevaluate the routes, doses, and applicability proposed for using gestrinone, including its use in new conditions such as menopause, lipedema, and sarcopenia. Here, we present the possible application of gestrinone as a long-acting therapeutic possibility through hormonal implants and the benefits and potential risks. Available evidence on the safety of doses and routes is limited. Gestrinone appears to be effective compared to other progestins and may have some advantages in the treatment of estrogen-dependent pathologies. Future research must evaluate gestrinone’s long-term safety and potential therapeutic indications. Full article
(This article belongs to the Special Issue Current Therapies for Endometriosis, Adenomyosis and Endometrial Cancer)
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20 pages, 642 KiB  
Systematic Review
Shared Pathogenic and Therapeutic Characteristics of Endometriosis, Adenomyosis, and Endometrial Cancer: A Comprehensive Literature Review
by Melinda-Ildiko Mitranovici, Diana Maria Chiorean, Liviu Moraru, Raluca Moraru, Laura Caravia, Andreea Taisia Tiron, Titiana Cornelia Cotoi, Havva Serap Toru and Ovidiu Simion Cotoi
Pharmaceuticals 2024, 17(3), 311; https://doi.org/10.3390/ph17030311 - 28 Feb 2024
Cited by 2 | Viewed by 3551
Abstract
Endometriosis and adenomyosis behave similarly to cancer. No current treatments represent a cure, even if there are several options, including hormonal and surgical therapy. In advanced or recurrent pathologies, however, personalized treatment is necessary. We have found that due to the multiple common [...] Read more.
Endometriosis and adenomyosis behave similarly to cancer. No current treatments represent a cure, even if there are several options, including hormonal and surgical therapy. In advanced or recurrent pathologies, however, personalized treatment is necessary. We have found that due to the multiple common features, various therapeutic options have been used or studied for all three pathologies, with varying results. The objective of this review is to extract from the relevant literature the compounds that are used for endometriosis and adenomyosis characterized by malignant behavior, with some of these drugs being studied first in the treatment of endometrial cancer. Special attention is needed in the pathogenesis of these pathologies. Despite the multiple drugs that have been tested, only a few of them have been introduced into clinical practice. An unmet need is the cure of these diseases. Long-time treatment is necessary because symptoms persist, and surgery is often followed by postoperative recurrence. We emphasize the need for new, effective, long-term treatments based on pathogeny while considering their adverse effects. Full article
(This article belongs to the Special Issue Current Therapies for Endometriosis, Adenomyosis and Endometrial Cancer)
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