Endometriosis and Adenomyosis, Hormonal Therapy in Gynecology
1. Aidarbek kyzy Aidanek
2. Hemant Sundesha
Dipesh Solanki
Avinash Vishnoi
(1. Teacher, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic.
2. Students, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic.)
Abstract
Endometriosis and adenomyosis represent two of the most prevalent estrogen-dependent gynecological disorders affecting women during their reproductive years, with substantial implications for quality of life, fertility, and psychological wellbeing. This comprehensive review examines the pathophysiological mechanisms underlying these conditions and critically evaluates contemporary hormonal therapeutic strategies. Drawing upon recent international guidelines and systematic evidence, we analyze the efficacy, safety profiles, and clinical positioning of progestin-based therapies, gonadotropin-releasing hormone analogs, combined oral contraceptives, and emerging pharmacological interventions. The analysis reveals that while no single hormonal agent demonstrates consistent superiority, sustained ovarian suppression forms the cornerstone of both symptomatic management and recurrence prevention. Progesterone resistance emerges as a critical therapeutic challenge, necessitating personalized treatment approaches and long-term management strategies. The integration of hormonal therapy within multidisciplinary care frameworks, addressing both physical symptoms and psychological comorbidities, represents the optimal contemporary paradigm for managing these chronic conditions. Future directions include the development of novel agents targeting specific molecular pathways and the refinement of predictive biomarkers to guide individualized therapy selection.
Introduction
The landscape of gynecological endocrinology has been fundamentally transformed over recent decades by deepening insights into the molecular pathogenesis of estrogen-dependent disorders and the corresponding evolution of targeted hormonal interventions. Among these conditions, endometriosis and adenomyosis stand as particularly challenging clinical entities, sharing common histological features of ectopic endometrial tissue while differing in anatomical distribution, symptomatic presentation, and therapeutic considerations. Endometriosis, characterized by the presence of endometrial-like tissue outside the uterine cavity, affects approximately 5% of women globally, with prevalence rising to 38% among infertile populations and 18-42% among women presenting with gynecological symptoms. Adenomyosis, representing the invasion of endometrial glands and stroma into the myometrium, demonstrates a pooled prevalence of 15-17% depending on histological subtype, with similarly elevated frequencies among symptomatic and infertile cohorts. These conditions impose substantial burdens upon affected individuals, manifesting through chronic pelvic pain, dysmenorrhea, dyspareunia, heavy menstrual bleeding, and infertility, while simultaneously generating significant psychological distress including anxiety, depression, and social isolation.
The therapeutic management of endometriosis and adenomyosis has historically oscillated between surgical and medical approaches, with contemporary consensus increasingly favoring hormonal suppression as first-line intervention for symptomatic disease. This paradigm shift reflects growing recognition of the chronic, recurrent nature of these conditions and the limitations of surgical intervention in providing durable symptom resolution. The 2024 German S3 Guideline on Endometriosis and the 2024 Korean Society of Endometriosis recommendations establish hormonal therapy as foundational to symptomatic management, while acknowledging the necessity of individualized treatment selection based on symptom severity, reproductive intentions, comorbidities, and patient preferences. The emergence of novel pharmacological agents, including oral gonadotropin-releasing hormone antagonists and refined progestin formulations, has expanded therapeutic options while simultaneously complicating clinical decision-making through the proliferation of available interventions.
This review aims to provide a comprehensive analysis of hormonal therapy in endometriosis and adenomyosis, integrating pathophysiological principles with clinical evidence to guide therapeutic selection. We examine the molecular mechanisms driving disease persistence and progression, with particular attention to estrogen dependence and progesterone resistance as critical determinants of treatment response. The pharmacological properties, efficacy profiles, and safety considerations of major hormonal drug classes are systematically evaluated, supported by evidence from randomized controlled trials, systematic reviews, and contemporary clinical guidelines. Special consideration is given to challenging clinical scenarios including deep infiltrating endometriosis, fertility preservation, adolescent patients, and postmenopausal persistence of disease. Through this synthesis, we seek to illuminate both current best practices and emerging directions in the hormonal management of these complex, chronic gynecological conditions.
Pathophysiological Foundations
Understanding the molecular underpinnings of endometriosis and adenomyosis is essential for rational therapeutic selection and the anticipation of treatment response. Both conditions demonstrate fundamental dependence upon estrogen signaling for lesion establishment, growth, and maintenance, while simultaneously exhibiting varying degrees of resistance to progesterone-mediated differentiation and growth inhibition. This hormonal milieu creates a permissive environment for ectopic endometrial proliferation, inflammatory activation, and the generation of pain symptomatology.
The pathogenesis of endometriosis involves multiple interconnected mechanisms, with retrograde menstruation representing the most widely accepted initiating event. However, the mere presence of refluxed endometrial tissue is insufficient for lesion establishment, as evidenced by the universal occurrence of retrograde menstruation contrasted against the 5% population prevalence of endometriosis. Successful implantation requires aberrant adhesive properties, enhanced invasive capacity, resistance to immune surveillance, and dysregulated angiogenesis. Endometrial mesenchymal stem cells and epithelial progenitors contribute critically to lesion establishment through their capacity for adhesion to peritoneal surfaces, proliferation, and differentiation into ectopic tissue. The molecular dysregulation underlying these processes involves aberrant expression of adhesion molecules including integrins and cadherins, upregulation of matrix metalloproteinases facilitating extracellular matrix degradation, and activation of survival pathways including PI3K/Akt and Wnt/β-catenin signaling.
Central to the hormonal dependence of endometriosis is the local estrogen environment within ectopic lesions. Aromatase activity, absent in normal endometrium, is aberrantly expressed in endometriotic tissue, enabling local conversion of androgens to estrogens and creating a self-sustaining cycle of estrogen production. This local hyperestrogenism is further amplified by prostaglandin E2-mediated upregulation of aromatase expression, establishing a positive feedback loop that promotes lesion growth and inflammatory activation. Estrogen receptor beta is overexpressed in endometriotic lesions relative to eutopic endometrium, contributing to estrogen-mediated proliferation while paradoxically suppressing estrogen receptor alpha-mediated induction of progesterone receptor expression.
Progesterone resistance represents perhaps the most significant therapeutic challenge in endometriosis management. Normally, progesterone induces secretory transformation of the endometrium, suppresses proliferation, and promotes differentiation through the progesterone receptor-mediated activation of target genes. In endometriosis, this signaling is fundamentally impaired through multiple mechanisms. Progesterone receptor B, the transcriptionally active isoform, is downregulated in ectopic lesions and often in eutopic endometrium of affected women, while progesterone receptor A, which can function as a transcriptional repressor, becomes predominant. This imbalance is mediated by epigenetic modifications including DNA hypermethylation of the progesterone receptor B promoter, driven by chronic inflammatory signaling through nuclear factor-kappa B activation. The proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1 beta, elevated in the peritoneal fluid of women with endometriosis, directly contribute to progesterone receptor suppression and impaired progesterone responsiveness.
The downstream consequences of progesterone resistance extend beyond mere proliferative disinhibition. The progesterone-regulated Indian hedgehog-COUP-TFII-WNT4 pathway, critical for epithelial proliferation control and stromal decidualization, is disrupted in endometriosis, contributing to both lesion persistence and endometrial non-receptivity. Insulin-like growth factor binding protein-1, a classical marker of decidualization, shows nearly two-fold reduction in endometriosis, reflecting impaired progesterone action. These molecular alterations have direct clinical implications, as they underlie both the therapeutic efficacy of progestin-based interventions and the phenomenon of progestin resistance observed in a subset of patients.
Adenomyosis shares fundamental pathophysiological features with endometriosis while demonstrating distinct anatomical and clinical characteristics. The prevailing model of adenomyosis pathogenesis involves invagination of the endometrial basalis into the myometrium, with recent molecular evidence supporting the role of endometrial epithelial and stromal progenitor cells in lesion establishment. The junctional zone, the inner myometrial layer adjacent to the endometrium, plays a critical role in disease initiation through trauma-induced activation of tissue injury and repair mechanisms. Hyperestrogenism and progesterone resistance similarly characterize adenomyotic tissue, driving enhanced proliferation, reduced apoptosis, and increased invasive capacity of endometrial cells.
The neuroangiogenic processes underlying pain generation in both conditions involve complex interactions between inflammatory mediators and neural elements. Nerve growth factors, substance P, and other neurogenic mediators are elevated in ectopic lesions, contributing to the sensitization of nociceptors and the development of chronic pain states. The inflammatory microenvironment, characterized by activated macrophages producing excessive cytokines and diminished natural killer cell function permitting immune evasion, perpetuates both tissue damage and symptom generation. These pathophysiological insights inform therapeutic targeting, as effective hormonal intervention must address not merely estrogen suppression but also the inflammatory and neurogenic components of disease.
Pharmacological Interventions and Clinical Evidence
The contemporary therapeutic armamentarium for endometriosis and adenomyosis encompasses multiple drug classes targeting distinct points in the hypothalamic-pituitary-gonadal axis and peripheral estrogen metabolism. The 2024 German S3 Guideline establishes progestins and oral gonadotropin-releasing hormone antagonists as first-line options for symptomatic endometriosis-related pain, with second-line alternatives including combined oral contraceptives, other progestins, gonadotropin-releasing hormone agonists, and aromatase inhibitors. For adenomyosis, all established hormonal therapies demonstrate efficacy without evidence supporting superiority of any single agent class.
Progestin-based therapies constitute the most widely utilized hormonal interventions, offering the advantages of oral administration, favorable cost profiles, and extensive clinical experience. Dienogest, a 19-nortestosterone derivative with high progesterone receptor selectivity and minimal androgenic activity, has emerged as a preferred progestin for endometriosis treatment. The efficacy of dienogest in reducing endometriosis-associated pain has been demonstrated in multiple randomized trials, with symptom improvement comparable to gonadotropin-releasing hormone agonists but substantially better tolerability. The drug achieves lesion regression through direct antiproliferative effects on endometriotic tissue, suppression of matrix metalloproteinase expression, and inhibition of neurogenic inflammation, independent of its ovulation-suppressing properties. Long-term administration up to five years has demonstrated sustained efficacy with acceptable safety profiles, though monitoring for bone mineral density effects is recommended for extended use.
Medroxyprogesterone acetate and norethisterone represent alternative progestin options, with demonstrated efficacy in pain reduction and lesion suppression. These agents may be particularly useful when dienogest is unavailable or poorly tolerated, though their androgenic side effect profiles and metabolic effects require consideration in patient selection. Desogestrel and drospirenone, available in many regions for long-term use, offer additional progestin choices with favorable tolerability characteristics. The levonorgestrel-releasing intrauterine system provides localized progestin delivery with particular utility in adenomyosis, where it achieves substantial reduction in menstrual bleeding and dysmenorrhea through endometrial decidualization and atrophy. Comparative studies between levonorgestrel intrauterine system and dienogest in adenomyosis demonstrate comparable pain relief efficacy, with the intrauterine system showing superior menstrual flow reduction but higher rates of device-related adverse events including expulsion in the context of enlarged uteri.
The recognition of progesterone resistance as a clinical phenomenon has prompted investigation into strategies to overcome or circumvent this therapeutic limitation. For patients demonstrating inadequate response to standard progestin doses, dose escalation or continuous administration regimens may achieve improved symptom control. The addition of estrogen-lowering agents to progestin therapy represents an alternative approach, with combination therapy potentially overcoming resistance through more profound hormonal suppression. However, the identification of true progestin resistance versus inadequate dosing, poor adherence, or alternative pain mechanisms remains clinically challenging and may require therapeutic trial periods of sufficient duration.
Gonadotropin-releasing hormone agonists have occupied a central position in endometriosis therapy since their introduction, achieving profound hypoestrogenism through pituitary receptor downregulation and suppression of ovarian steroidogenesis. The development of depot formulations including leuprolide acetate, goserelin, and triptorelin enabled monthly or quarterly administration, improving convenience while maintaining efficacy. Randomized trials consistently demonstrate equivalence to danazol in symptom reduction and lesion regression, without the androgenic and metabolic adverse effects that limited danazol's utility. However, the hypoestrogenic side effect profile including vasomotor symptoms, vaginal dryness, and bone mineral density loss has restricted monotherapy duration to six months in most guidelines.
The introduction of add-back therapy transformed gonadotropin-releasing hormone agonist utilization, permitting extension of treatment duration while mitigating estrogen deficiency consequences. Low-dose estrogen-progestin combinations administered concomitantly with agonist therapy maintain bone mineral density and improve tolerability without compromising therapeutic efficacy against endometriotic lesions. Current guidelines uniformly recommend add-back therapy when gonadotropin-releasing hormone agonists are prescribed, with treatment duration extendable to twelve months when appropriate add-back is utilized. The optimal add-back regimen remains subject to some debate, though norethisterone acetate-containing combinations have been most extensively studied and are widely recommended.
The recent development of oral gonadotropin-releasing hormone antagonists represents a significant pharmacological advance, offering several theoretical advantages over agonist therapy. These small-molecule, non-peptide agents achieve immediate receptor blockade without the initial flare effect observed with agonists, permit dose-dependent ovarian suppression allowing therapeutic titration, and demonstrate more rapid reversibility upon discontinuation. Relugolix, administered in combination with estradiol and norethisterone acetate add-back, has demonstrated efficacy in reducing endometriosis-associated pain in phase III trials, with regulatory approval for this indication in multiple jurisdictions. Linzagolix offers an alternative oral antagonist with flexible dosing options including both add-back and non-add-back regimens, allowing individualized treatment based on symptom severity and bone health considerations. The 2024 German guidelines position these agents as first-line options when preceded by surgical diagnosis, or as second-line alternatives following progestin failure.
Aromatase inhibitors represent a specialized therapeutic option for refractory endometriosis, targeting the local estrogen production within ectopic lesions that persists despite ovarian suppression. Anastrozole and letrozole, when administered in combination with progestins, gonadotropin-releasing hormone analogs, or combined oral contraceptives, achieve more profound estrogen suppression than ovarian suppression alone. Meta-analyses demonstrate significant pain reduction and quality of life improvement with aromatase inhibitor combination therapy in patients failing other hormonal interventions. The European Society of Human Reproduction and Embryology guidelines specifically recommend aromatase inhibitor combination therapy for pain associated with drug-resistant and surgery-resistant rectovaginal endometriosis. Bone mineral density monitoring is essential during aromatase inhibitor therapy given the profound estrogen suppression achieved.
Combined oral contraceptives maintain an important position in endometriosis and adenomyosis management, particularly as second-line therapy or for patients desiring contraception concurrent with disease treatment. Continuous or extended-cycle regimens, eliminating the hormone-free interval, achieve greater symptom suppression than conventional cyclic administration through sustained ovarian inhibition and endometrial atrophy. The 2024 German guidelines specifically recommend long-cycle combined oral contraceptive regimens over conventional use for menstruation-associated complaints including dysmenorrhea. The favorable impact of combined oral contraceptives on adolescent patients, providing both symptom relief and contraceptive benefits, makes them particularly suitable for this population, though evidence specifically supporting efficacy in adolescent endometriosis remains limited.
Special Clinical Considerations
The management of deep infiltrating endometriosis presents particular challenges given the extensive fibrotic and invasive nature of these lesions. While hormonal therapy achieves symptom improvement in many patients, complete lesion regression is rarely observed, and surgical intervention remains necessary for definitive anatomical correction in selected cases. The 2024 guidelines emphasize that postoperative hormonal therapy is essential following surgical management of deep infiltrating disease, with recurrence rates substantially higher in the absence of medical suppression. Combined treatment approaches achieving cure rates of approximately 60% in some series, compared to 50-55% for surgery or hormones alone, underscore the importance of multimodal management.
Fertility considerations fundamentally influence therapeutic decision-making in endometriosis and adenomyosis. Medical therapy, while effective for symptom control, does not improve fertility outcomes and indeed prevents conception through ovulation suppression. For patients desiring pregnancy, treatment intervals must be carefully planned to balance symptom control with fertility optimization. Pre-treatment with gonadotropin-releasing hormone agonists prior to in vitro fertilization has been advocated based on historical data suggesting improved pregnancy rates, though more recent randomized evidence has failed to confirm significant benefit. Postoperative hormonal suppression following conservative surgery for ovarian endometriomas is recommended to prevent recurrence and preserve ovarian reserve, with long-term progestin therapy or combined oral contraceptives demonstrating reduction in endometrioma recurrence rates.
Adolescent endometriosis requires special consideration given the potential impact of hormonal interventions on developing physiology and the importance of maintaining fertility potential. The 2024 guidelines recommend conservative medical therapy as primary management for suspected endometriosis in adolescence, with combined oral contraceptives and nonsteroidal anti-inflammatory drugs forming the usual first-line approach. Long-cycle combined oral contraceptive regimens are specifically recommended for menstruation-associated complaints in this population. Laparoscopic evaluation is reserved for treatment-refractory cases, with surgical intervention preferably combined with diagnostic assessment in a single procedure. Gonadotropin-releasing hormone agonists should be used cautiously in adolescents given concerns regarding effects on developing bone, with limited available data supporting their safety in this population.
Postmenopausal endometriosis, though less common given the estrogen-dependent nature of the disease, may persist or present de novo in women receiving hormone therapy. The 2024 Korean guidelines acknowledge that endometriotic symptoms may persist after menopause and treatment may remain necessary. For women with a history of endometriosis undergoing hysterectomy and experiencing vasomotor symptoms, progestogen combination with estrogen therapy is recommended considering the elevated risk of malignant transformation. Tibolone may serve as a second-line option for patients unable to tolerate continuous combined estrogen-progestogen therapy. Women experiencing surgical menopause at young ages should receive continuous combined estrogen-progestogen hormone therapy until the natural age of menopause to mitigate cardiovascular and bone health risks.
Recurrence Prevention and Long-Term Management
The chronic, recurrent nature of endometriosis and adenomyosis necessitates long-term management strategies extending beyond initial symptom resolution. Postoperative recurrence rates demonstrate the limitations of surgical intervention alone, with pain relapse reported in 20-26% of patients within the first postoperative year and lesion reappearance in 12-29% at one to two years. Systematic reviews indicate that postoperative hormonal therapy reduces lesion recurrence risk by 59-70% and symptom recurrence by approximately 30% compared to surgery alone, establishing medical suppression as essential adjunctive therapy.
The duration of postoperative hormonal therapy significantly influences recurrence rates, with treatment periods shorter than twelve months demonstrating recurrence risks comparable to untreated patients within one to two years of discontinuation. This observation suggests that hormonal therapy achieves suppressive rather than curative effects, requiring sustained administration to maintain benefit. Continuous combined oral contraceptive regimens following laparoscopy demonstrate superior dysmenorrhea relapse prevention compared to cyclic administration, supporting extended-cycle approaches for recurrence prevention.
Despite the established benefits of postoperative hormonal therapy, adherence represents a significant challenge, with discontinuation rates high due to side effects, cost considerations, or desire for pregnancy. Furthermore, emerging evidence suggests that some patients may develop resistance to progestin therapy over time, potentially reflecting progressive progesterone receptor downregulation or the evolution of centrally-mediated pain mechanisms less responsive to hormonal suppression. These limitations underscore the need for ongoing research into alternative therapeutic strategies and predictive biomarkers to identify patients most likely to benefit from specific interventions.
The phenomenon of minimal residual disease following surgical intervention contributes to early recurrence, particularly in deep infiltrating endometriosis where complete excision may be technically challenging. Positive resection margins and microscopic satellite lesions adjacent to resection sites carry significant recurrence risk, though the relationship between surgical completeness and long-term outcomes remains complex. Hormonal suppression may maintain residual lesions in a dormant state, with recurrence manifesting upon treatment discontinuation as these lesions reactivate and proliferate. This biological understanding supports recommendations for extended or indefinite hormonal therapy in patients with significant residual disease burden or high recurrence risk profiles.
Safety Considerations and Monitoring
The long-term safety of hormonal therapy for endometriosis and adenomyosis requires careful consideration, particularly given the extended treatment durations often necessary for effective disease management. Bone mineral density represents the most significant safety concern for therapies achieving profound estrogen suppression. Gonadotropin-releasing hormone agonist monotherapy causes significant bone loss, with lumbar spine density decreasing by approximately 5% over six months of treatment. Add-back therapy substantially mitigates this effect, though monitoring remains prudent for extended treatment courses. Aromatase inhibitor combination therapy similarly requires bone health surveillance, with dual-energy x-ray absorptiometry recommended at treatment initiation and periodic intervals thereafter.
Cardiovascular considerations influence hormonal therapy selection, particularly in patients with additional risk factors. Combined oral contraceptives and estrogen-containing add-back regimens carry thromboembolic risk requiring assessment of individual patient risk profiles. Progestin-only therapies avoid estrogen-related cardiovascular risks while maintaining efficacy, potentially offering preferable options for patients with contraindications to estrogen exposure. The metabolic effects of various progestins differ substantially, with androgenic progestins potentially adversely affecting lipid profiles and insulin sensitivity compared to less androgenic alternatives.
The potential for malignant transformation, though rare, influences management decisions particularly in postmenopausal patients with persistent endometriosis. Endometrioid adenocarcinoma arising in endometriotic lesions, while uncommon, demonstrates association with unopposed estrogen exposure and prolonged disease duration. This risk supports the inclusion of progestogen in hormone therapy regimens for menopausal women with endometriosis history, counterbalancing the proliferative effects of estrogen replacement.
Psychological wellbeing represents an essential consideration in long-term hormonal therapy, given the high prevalence of anxiety and depression among women with endometriosis and adenomyosis. While hormonal therapies may indirectly improve psychological health through symptom relief, some agents may adversely affect mood in susceptible individuals. The selection of well-tolerated hormonal regimens and attention to psychological comorbidities within integrated care models optimizes overall treatment outcomes.
Future Directions and Emerging Therapies
The evolving understanding of endometriosis and adenomyosis pathophysiology is driving development of novel therapeutic approaches targeting specific molecular pathways beyond global hormonal suppression. Selective progesterone receptor modulators, including asoprisnil and ulipristal acetate, have demonstrated preliminary efficacy in symptom reduction through mixed agonist-antagonist effects on progesterone receptor signaling. While regulatory challenges have limited their clinical availability, continued development of this drug class may offer alternatives for patients with progestin resistance or intolerance.
Targeting specific inflammatory and neurogenic pathways represents another promising therapeutic direction. Given the central role of prostaglandin E2 in both pain generation and estrogen production within lesions, selective prostaglandin pathway inhibitors may achieve symptomatic benefit with fewer systemic effects than hormonal suppression. Similarly, agents targeting nerve growth factor or other neurogenic mediators may address the pain component of disease more specifically than current hormonal approaches.
The identification of biomarkers predictive of treatment response would enable personalized therapy selection, matching individual patients with the interventions most likely to achieve benefit. Genetic polymorphisms affecting steroid hormone metabolism and receptor function may influence treatment responsiveness, suggesting potential for pharmacogenomic approaches to guide therapy. Non-invasive biomarkers reflecting lesion burden or inflammatory activity could facilitate treatment monitoring and early identification of recurrence, enabling timely intervention adjustment.
Immunomodulatory therapies targeting the immune dysfunction underlying lesion establishment and persistence represent an emerging frontier. Given the role of altered macrophage function, diminished natural killer cell activity, and chronic inflammation in disease pathogenesis, agents restoring normal immune surveillance or suppressing pathological inflammatory activation may complement hormonal approaches. The integration of such targeted therapies with conventional hormonal suppression may achieve superior outcomes while reducing the need for profound estrogen deprivation and its associated adverse effects.
Conclusion
The hormonal management of endometriosis and adenomyosis has evolved substantially, with contemporary practice guided by robust evidence supporting the efficacy of sustained ovarian suppression for symptom control and recurrence prevention. Progestin-based therapies, including dienogest and the levonorgestrel-releasing intrauterine system, occupy central positions in first-line management, offering favorable efficacy-tolerability profiles suitable for long-term administration. The emergence of oral gonadotropin-releasing hormone antagonists expands therapeutic options, providing flexible, rapidly reversible alternatives to traditional agonist therapy. The critical recognition of progesterone resistance as a pathophysiological and clinical phenomenon necessitates individualized treatment approaches, with combination therapies and dose optimization strategies addressing refractory disease.
The integration of hormonal therapy within comprehensive, multidisciplinary care models addressing both physical symptoms and psychological wellbeing represents optimal contemporary practice. Long-term management strategies must balance sustained disease suppression with safety considerations, particularly regarding bone health and cardiovascular risk. Future therapeutic development targeting specific molecular pathways promises to refine and expand treatment options, potentially overcoming current limitations including progestin resistance and the need for indefinite hormonal suppression in many patients. Through continued research and evidence-based clinical application, the burden of these chronic, challenging gynecological conditions may be progressively reduced, improving quality of life for the substantial population of affected women worldwide.
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