Seminars in reproductive endocrinology最新文献

The human corpus luteum (CL) is a transient endocrine gland regulated primarily by the age-dependent action of LH/hCG, which initiates a series of cell-specific processes necessary for the structure and also function of the gland. An extensive local regulation of the luteal function also exists, based on the heterogeneity of the cellular composition of the CL. It is most likely that interactions occur among the different subpopulations of steroidogenic (large and small luteal cells) and nonsteroidogenic cells (leukocytes, endothelial cells, and fibroblasts). Therefore, local produced substances, including steroids, growth factors, reactive oxygen species, and, recently, nitric oxide, may modulate luteal life span. The knowledge of the basic events involved in the control of human luteal function may lead to a better understanding of the physiopathology of the human menstrual cycle.

Immune cells of myeloid and lymphoid lineages constitute a significant cell mass in the corpus luteum. Changes in the distribution and numbers of these cells within the corpus luteum take place during the life span of the corpus luteum. These cells are now recognized to be important both in structural changes of the corpus luteum as well as in the regulation of steroidogenesis. Cytokines are secreted from immune cells and other cells of the corpus luteum and comprise an important component of the intercellular signaling that is regulating tissue remodeling and the endocrine activity of the gland. This review covers recent findings of the participation of immune cells and cytokines in the regulation of the corpus luteum function.

Although a limited number of drugs make up the mainstay of treatment of endometriosis, many alternative medications have been used in an attempt to improve efficacy. Some have been rigorously evaluated and are of proven benefit, while others show promise in preliminary trials or in animal models. Proper methods of evaluating medical therapy and outcomes are essential. This chapter provides a review of new medical therapies for the treatment of endometriosis and their evaluation.

The contrasting findings obtained in the studies that have attempted to correlate the stage of endometriosis with severity of pain symptoms suggest that some specific characteristics of the lesions are more implicated in the genesis of pain than disease extension per se. Thus, fresh, metabolically active, intraperitoneal implants may cause functional pain symptoms such as dysmenorrhea, whereas infiltrating, nodular and fibrotic lesions are responsible for organic-type pain such as deep dyspareunia. Women with symptomatic endometriosis seem to have reduced peripheral beta-endorphin production in comparison with pain patients without the disease, although neuroendocrine modulation of pelvic nociceptive stimuli is far from clear. There is little evidence to support the notion that specific psychiatric features render some women more vulnerable to developing endometriosis, as results from investigations performed on women with asymptomatic lesions are very similar to normative data. Moreover, it appears that the psychological profile of symptomatic patients with the disease is no different from those with pain and a normal pelvis or other gynecological conditions. Consequently, the local biochemical and physical effects of lesions seem to be the most important factors in determining frequency and severity of symptoms.

The absolute risk of endometrioid carcinoma of the ovary is very small. When endometriosis is left behind at the time of hysterectomy, there may be increased risk and difficulties in hormone replacement management.

The choice of treatment options for endometriosis-associated infertility has been both controversial and complex, largely because of lack of data. In the last 10 years, better data from numerous studies with improved design support laparoscopic ablation and/or resection of lesions as the most successful for both minimal/mild and moderate/severe/extensive disease. Laparotomy should be performed when necessary. Observation alone is sometimes indicated in young women with minimal/mild disease. Hormonal suppression has no identifiable role, except perhaps for severe/extensive disease, before IVF or GIFT. Ovarian stimulation with clomiphene or gonadotropins and concomitant intrauterine insemination is indicated for minimal/mild disease. IVF and GIFT are often best for those who have failed other treatments, have advanced age, prolonged infertility, and/or multiple-factor infertility.

The corpus luteum (CL) is an organ that exhibits extremely rapid growth, development, and regression during the course of each nonpregnant cycle. The CL consists of steroidogenic (parenchymal) and nonsteroidogenic (nonparenchymal) cells. The small and large parenchymal cells differ in numerous morphological and functional characteristics, and are thought to interact with each other to maintain normal luteal function. These steroidogenic luteal cells also interact with the nonsteroidogenic cells; for example, they produce factors that stimulate proliferation and migration of endothelial cells and proliferation of fibroblasts; they also may enhance or suppress immune cell function. Conversely, endothelial cells produce factors that modulate steroidogenesis, and immune cells produce cytokines that modify the secretory function of steroidogenic cells. Cellular interactions may be mediated by several mechanisms, including humoral (endocrine and paracrine) pathways as well as contact-dependent (gap junctional) pathways. Thus, hormones, growth factors and cytokines produced locally by steroidogenic or nonsteroidogenic cells may be transferred from cell to cell indirectly or directly to regulate luteal function. Gap junctions are present in luteal tissues of several species, and gap junctional intercellular communication is affected by the stage of luteal development and systemic and local regulators of luteal function. Such cellular interactions probably are important in luteal hormone production, signal transduction, angiogenesis, and luteolysis because of their role in coordinating function among the various luteal cell types.

There are many hypotheses concerning the pathogenesis of endometriosis, though no single theory can explain all cases. It is likely that several mechanisms are involved. Early studies concentrated on the histogenesis of the endometriotic lesion. Recent evidence has implicated components of the immune system in the pathogenesis of endometriosis. This review considers the evidence for different theories of the histogenesis of endometriosis and discusses possible immune factors that may be involved in the pathophysiology of the disease.

Classification systems for endometriosis continue to evolve. Past systems have been modeled primarily after those in use for grading malignant disease. Unfortunately, classification methods that attempted to quantitate the severity of disease have suffered from only modest predictability in determining outcome. The 1985 revised American Fertility Society classification system is limited by scoring arbitrariness, potential for observational error, limited reproductivity, failure to consider lesion morphologic type and a particularly poor correlation with pelvic pain. These shortcomings are being presently addressed.