Endometriosis is a chronic, estrogen-dependent inflammatory disorder characterized by ectopic endometrium-like tissue, leading to debilitating pain and reduced quality of life. Pain is the hallmark of endometriosis, with individuals experiencing dysmenorrhea, dysuria, dyschezia, dyspareunia, and chronic pelvic pain. However, pain does not always correlate with the severity or location of the lesions, which suggests additional factors are involved in the generation of endometriosis-associated pain. The underlying mechanisms are multifactorial, involving peripheral and central sensitization, inflammation, aberrant innervation, immune dysregulation, and hormonally influenced processes. Additionally, many individuals with endometriosis experience comorbid pain syndromes, including pelvic floor dysfunction (PFD), irritable bowel syndrome, interstitial cystitis, abdomino-pelvic myalgia, and vulvar vestibulodynia. These conditions share overlapping pathophysiological mechanisms, such as cross-sensitization of pelvic organs and maladaptive neuroplastic changes, further amplifying pain perception. Despite advances in understanding these mechanisms, current treatment strategies remain inadequate, with hormonal suppression and surgical intervention providing variable relief. A comprehensive, multimodal approach targeting neuroinflammatory pathways, PFD, and central sensitization may be essential for improving pain management. Further research is needed to refine therapeutic strategies and develop targeted interventions for this challenging condition.

Endometriomas affect up to 44% of women with endometriosis and are associated with chronic pelvic pain, infertility, and reduced ovarian reserve. Diagnosis and management are clinically challenging, requiring a nuanced understanding of imaging, clinical presentation, and patient goals. This review offers a comprehensive overview of the diagnosis and management of ovarian endometrioma, with a focus on clinical presentation, advanced diagnostic imaging, and treatment strategies. It addresses the complex balance between symptom relief, disease progression, fertility preservation, and long-term ovarian function, while also exploring emerging innovations in care. Endometriomas are often associated with significant pelvic pathology, including deep endometriosis and adenomyosis. Advanced imaging modalities, such as transvaginal ultrasound and magnetic resonance imaging, have significantly improved diagnostic accuracy. Management strategies range from surveillance in asymptomatic patients to medical therapy for symptom control. Surgical options of laparoscopic cystectomy remain the gold standard for patients with pain, infertility, or concerning imaging findings, but do carry the risk of affecting ovarian reserve. Emerging evidence suggests that conservative surgical techniques and postoperative hormonal therapy may reduce recurrence rates. Endometriomas represent a complex gynecological condition requiring individualized management strategies. Future research should focus on biomarkers for diagnosis and recurrence prediction, refining noninvasive diagnostic tools, and optimizing surgical techniques to minimize ovarian damage.

Endometriosis affects millions of women around the world, yet it remains a complex and often misunderstood condition, with limited funding available for research. Although much about this enigmatic disease is still unknown, emerging data continue to shed light on its mechanisms, leading to improved understanding and better management options for patients. While advances have been made in understanding the symptoms and pathophysiology of endometriosis, one critical area remains underexplored: its impact on fertility. It is now well established that endometriosis can significantly impair fertility, posing additional challenges for women trying to conceive. This study explores current theories on how endometriosis affects reproductive function and highlights the latest research on both medical and surgical approaches to managing infertility in these patients. It will also examine the implications of endometriosis on natural conception as well as outcomes related to assisted reproductive technologies.

Endometriosis affects an estimated 200 million women globally, yet significant barriers hinder access to timely and appropriate care. These barriers encompass various aspects, including societal normalization of menstrual pain, leading to delayed diagnosis and misinterpretation of symptoms as "normal" period pain. This normalization, coupled with the stigma surrounding menstrual health, often results in the dismissal of symptoms by both individuals and healthcare providers. Furthermore, access is often limited by socioeconomic factors and healthcare disparities, making specialized treatments financially prohibitive for many. There is an urgent need for a multi-pronged approach to improve access to quality endometriosis care. This includes increased education and awareness for patients, healthcare providers, and the public to destigmatize the condition and promote early recognition of symptoms. Additionally, addressing healthcare system reforms and socioeconomic disparities is essential to ensuring equitable access to effective diagnostic tools and treatment options for all affected individuals. Further research is crucial to better understand the underlying mechanisms of the disease, improve diagnostic tools, and develop more effective treatments.

Endometriosis-the growth of uterine-like tissue outside the uterus-is a devastating disease that severely reduces the quality of life of those affected, resulting in missed days from school and work due to intractable pelvic pain. While endometriosis was first recognized over 100 years ago, we still do not fully understand the mechanisms of the disease, and most treatments address the symptoms of pain and discomfort but do not prevent lesion growth or disease progression. Endometriosis is a significant cause of infertility; 50% of patients seeking fertility care have endometriosis. Definitive diagnosis typically requires histological examination of excised lesional tissue, necessitating surgical excision of lesions. Therefore, many patients have a significant diagnosis delay-up to 11 years following the first onset of symptoms. While modern research technologies hold the potential to vastly improve diagnosis and treatment, women's health, particularly genitopelvic health, is understudied and underfunded. Here, we summarize what is currently known about the mechanism and ongoing efforts to develop new biomarkers and therapies that target the root causes of disease.

Menopausal symptoms, particularly vasomotor symptoms (VMS) and genitourinary syndrome of menopause (GSM), significantly affect women's quality of life (QoL). While menopausal hormone therapy (MHT) is the most effective treatment, contraindications such as estrogen-sensitive cancers and thromboembolic conditions limit its use for many women. This review explores alternative nonhormonal treatments, including pharmacological options like selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, gabapentin, clonidine, and neurokinin receptor antagonists (e.g., fezolinetant), alongside nonpharmacological approaches such as lifestyle modifications, cognitive-behavioral therapy, and acupuncture. These alternatives, though less effective than MHT, provide critical options for women unable to use hormonal therapies. Emerging treatments like fezolinetant demonstrate promise in reducing VMS by addressing the underlying pathophysiology, but safety concerns, such as hepatotoxicity, require ongoing monitoring. GSM management includes therapies such as vaginal estrogens, prasterone, and ospemifene, with tailored approaches necessary for cancer survivors. Emphasis is placed on individualized care, better patient education, and continued research into the safety and efficacy of these therapies to improve the QoL for postmenopausal women.

Perimenopausal women have specific needs when it comes to contraception. Although fertility rates generally decrease after age 40, pregnancy is still possible and may be associated with a higher risk of obstetric and fetal complications. Moreover, women may experience bothersome symptoms during perimenopause due to anovulatory cycles and fluctuating estrogen levels, such as abnormal uterine bleeding, vasomotor symptoms, migraines, and mood disorders. Additionally, age increases the risk of the most common side effects of well-known contraceptives, particularly those containing estrogen. For this reason, contraception counseling during perimenopause should be tailored to the woman's characteristics. It should include three steps: evaluating the woman's needs and symptoms; evaluating the potential benefits of the chosen method; evaluating risk factors that may contraindicate certain choices. No contraceptive method is contraindicated solely based on age. Among combined hormonal contraceptives, if no contraindication exists, natural estrogens should be preferred after 40 years old. On the other hand, progestin-only methods can also be safely used in the presence of cardiovascular risk factors. This review will address the main reasons why a woman may need an HC method and how to make a tailored and informed choice.

Menopause represents a cardio-metabolic transition, but cardiovascular (CV) health in women is highly influenced by other reproductive milestones and conditions, which delineate a cardio-reproductive lifeline. Reproductive history represents an opportunity to identify women at elevated risk of CV events after menopause, going beyond traditional CV risk factors. This review aims to summarize the impact of reproductive milestones, gynecological conditions, and pregnancy-related factors on cardio-metabolic health at midlife. The main physio-pathological mechanisms likely implicated in linking reproductive events and CV disease risk are described, as well as the impact of specific conditions (early/late menarche and menstrual dysfunction [functional hypothalamic amenorrhea, polycystic ovary syndrome, benign gynecological conditions (endometriosis, adenomyosis, and fibroids), infertility, adverse pregnancy outcomes, and premature/early natural or surgical menopause]). Data indicate that a reproductive checklist in midlife women is warranted for primary prevention and intervention.

Estrogens, including estradiol and estrone, and androgens, including testosterone, are locally produced in adipose tissue throughout a woman's lifespan. Already in fertile-aged women, subcutaneous and visceral adipose tissue produce notable amounts of estrogens despite ongoing ovarian estrogen synthesis. After menopause, adipose tissue becomes the most important producer of estrogens. A decrease in circulating estrogen concentrations coincides with a relative increase in the amount of visceral adipose tissue and an increased risk for metabolic disorders. Furthermore, local adipose tissue biosynthesis of sex steroids may regulate the distribution of adipose tissue between the subcutaneous and visceral depots. Further studies are needed to characterize the relation of local adipose tissue sex steroid milieu to local and circulating markers of adipose tissue and metabolic dysfunction. This can shed more light on the increasing adiposity and metabolic burden associated with menopause. Here, we discuss the roles estrogens and androgens play in adipose tissue distribution and function before and after menopause, and highlight the role of local sex steroid biosynthesis, or intracrinology, in determining local tissue sex steroid environments.

Progestogens (norethisterone acetate, medroxyprogesterone acetate, dydrogesterone, micronized progesterone, levonorgestrel, drospirenone, and trimegestone) added to estrogen for endometrial protection are reviewed. They can be given orally or vaginally, norethisterone acetate can also be given transdermally, and levonorgestrel can be given through the intrauterine route. Sequential use of progestogens protects the endometrium if exposure lasts for at least 12 days/month; longer intervals are not safe. Continuous use of progestogens, whether oral, transdermal, or intrauterine, provides the most effective protection. Progestogen addition is accompanied with significant elevations in breast cancer risk, the largest drawback of progestogen use, and dydrogesterone, micronized progesterone, and a levonorgestrel intrauterine device may be safest in this regard. Progestogens also double deep vein thrombosis risk and diminish the positive effect of estrogen on colorectal cancer and vascular health. Recent data imply a neutral effect of progestogens in combination with estrogen on Alzheimer's disease risk, but the risk of vascular dementia is decreased. In conclusion, progestogens are a double-edged sword, effectively protecting the endometrium but causing several side effects and reducing many estrogen-induced benefits. With modern endometrial diagnostic tools, the safety of low-dose unopposed estrogen regimens should be assessed in a prospective controlled trial in women with an intact uterus.

Given that menopause affects about half of the world's midlife population, it is crucial to understand its impact beyond traditional menopausal symptomology. For instance, many women, while transitioning through menopause, experience profound changes in body composition. These changes may contribute to postmenopausal reductions in metabolic health. This narrative review explores the influence of menopause on skeletal muscle and adipose tissue, highlighting the decline in muscle mass and strength and the gain and redistribution of adipose tissue, particularly the increase in visceral adiposity. Although menopausal changes in body composition are seemingly extensively studied, the longitudinal studies are not that common, and the precise mechanisms driving body composition changes remain unclear, with uncertainties surrounding the roles of hormonal shifts compared with regular aging, energy balance, and lifestyle factors. Notably, it remains debated whether menopause or estrogen meaningfully influences resting energy expenditure. The review also considers the potential mitigating effects of menopausal hormone therapy and regular exercise. Understanding these changes is essential for developing effective strategies to support women's health during and after menopause.

Although the average age of menopause in western women is 50 years, 10% of women experience menopause between the age of 40 and 44 (early menopause) and 2 to 3% before the age of 40 (premature ovarian insufficiency). Although the etiology of early-onset menopause varies, it remains unknown in most cases. The most common reasons are genetic factors or chromosomal abnormalities, cancer treatment, bilateral oophorectomy, and autoimmune diseases. Early or premature menopause can negatively impact a woman's long-term health. There is strong evidence that these conditions increase the risk of osteoporosis, cardiovascular disease (CVD) morbidity, and premature mortality. There is comparatively little evidence, however, on other associated health risks or on their potential for mitigation by hormone replacement therapy (HRT). In this review, we examine the literature on the long-term health of women with early-onset menopause, particularly its effects on morbidity, mortality, and quality of life. At-risk women and their physicians should be aware of the age-related risks of menopause to avoid or mitigate negative outcomes.

With the rising incidence of endometrial cancer, including among young women, and the trend of increasing age among first-time mothers, the need for safe and effective fertility-sparing treatments for endometrial cancer and atypical endometrial hyperplasia has become crucial. Focusing on studies from the past decade, this review synthesizes findings on the safety and outcomes of fertility-sparing treatments for endometrial cancer and atypical endometrial hyperplasia and provides an overview of current treatment recommendations. Fertility-sparing treatment, including hysteroscopic tumor resection followed by hormonal therapy with oral progestins and/or the insertion of a levonorgestrel-releasing intrauterine device, can be offered to a selected group of women of reproductive age who wish to preserve their ability to become pregnant in the future. The safety of conservative treatment for women diagnosed with Stage 1A, Grade 1 endometrial cancer without myometrial invasion is high; however, current evidence on the safety of this treatment for women with Grade 1, Stage 2 endometrial cancer is limited. Even though the success rate in terms of pregnancies and deliveries is high, it is not as high as in the general population, and women should be informed of the potential need for assisted reproductive technology.

Radiotherapy is an effective treatment for various cancers, but it can cause significant side effects on various organ systems, including the reproductive organs, which is a major concern for women of reproductive age. A well-known long-term effect of oncological treatment is premature ovarian insufficiency. Another critical but sometimes overlooked organ at risk in female cancer survivors is the uterus. This review focuses on the impact of radiotherapy on uterine physiology, highlighting key issues such as the development of fibrosis and loss of elasticity, vascular damage, and hormonal disruption, all of which can compromise uterine function. These changes can negatively impact fertility and pregnancy outcomes, such as miscarriage, preterm birth, and low birth weight. Limited evidence is also available suggesting that radiotherapy may affect endometrial receptivity and contribute to abnormal placentation. We conclude by discussing strategies aimed at mitigating the damage caused by radiotherapy, such as fertility-preserving treatments and hormonal interventions. A thorough understanding of these effects is essential for healthcare providers to offer informed support to women who wish to maintain their fertility and have children following cancer treatment.

Young women diagnosed with endometrial cancer may have a fertility wish and may, under certain conditions, be offered fertility-sparing treatment. However, they may also have underlying infertility issues, as anovulation, obesity, polycystic ovary syndrome, and advanced maternal age are often found in women with endometrial cancer or atypical hyperplasia. These fertility issues may hinder pregnancy or prolong the time to pregnancy, in a situation where not much time is allowed to try for a pregnancy. Referral to a reproductive specialist is recommended as early as possible to detect any possible underlying infertility issues that might require assisted reproductive technology once a pregnancy is allowed or may even contradict fertility-sparing treatment. Ovarian reserve testing is a tool used to assess a woman's ovarian reserve, although it cannot, as such, be used to predict the chance of pregnancy. In case of obesity, weight loss is recommended as soon as possible.

Borderline ovarian tumors (BOTs) are commonly diagnosed in women of reproductive age, raising concerns about the impact of surgical management on fertility. This review explores the role of fertility-sparing surgery (FSS) and fertility preservation (FP) strategies in young women diagnosed with BOTs. While FSS carries a slightly higher risk of recurrence compared to bilateral salpingo-oophorectomy, there is growing evidence supporting the safety of FSS, with no adverse effects on 10-year overall survival. In light of this, recent multidisciplinary guidelines recommend FSS for BOT at all stages. A significant proportion of women with BOTs report infertility prior to diagnosis, suggesting a possible pathophysiological link between reduced reproductive fitness and the development of BOT. The potential association between ovarian stimulation (OS) and an increased risk of BOT remains controversial, with current evidence failing to establish a definitive causal link. For women with recurrent stage I BOT and no evidence of peritoneal disease on imaging, OS followed by oocyte retrieval is a viable option before definitive surgery. Notably, a history of BOT does not significantly affect pregnancy outcomes following IVF. FP counseling is essential to tailor treatment plans that address both oncological and reproductive needs in patients undergoing FSS for BOT.

Cervical cancer (CC) is one of the most common malignancies affecting young women of childbearing age, making fertility preservation (FP) a pivotal consideration in its management. The feasibility of FP techniques depends on the cancer stage and oncological treatments. In early-stage CC, fertility-sparing surgery can be offered for young patients wishing to preserve fertility without compromising oncological safety. Neoadjuvant chemotherapy followed by fertility-sparing surgery is an alternative for patients with nonmetastatic locally advanced disease and negative lymph node status. Nevertheless, for patients with locally advanced disease requiring radical hysterectomy or pelvic radiotherapy, FP can be performed using oocyte, embryo, or ovarian tissue cryopreservation. For these patients, future pregnancy is possible through surrogacy. Recently, uterine transposition has been proposed as an alternative to preserve uterine anatomy to prevent uterine radio-induced damage and avoid surrogacy. This review provides a comprehensive overview of the FP options available for young patients with CC.