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Query: UMLS:C0021359 (infertility)
 26,075 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uterine leiomyomas are the most common benign tumours of the female genital tract, often necessitating hysterectomy. The most common symptoms are dysmenorrhoea, menorrhagia, infertility and abortion. Ovarian hormones seem to play an essential role in pathogenesis, and deprivation of ovarian oestrogen causes leiomyomas to shrink significantly. The purpose of this study was to evaluate the effects of the non-steroidal aromatase inhibitor letrozole on uterine leiomyomas and on bone metabolism. A prospective, open clinical trial was conducted in a university-based hospital. Sixteen premenopausal women with symptomatic uterine leiomyomas were treated with letrozole 5 mg/day orally for 3 months. The main outcome measures of uterine and uterine leiomyoma sizes, serum FSH, LH, oestradiol concentrations, ovarian volumes and myoma-related symptoms were noted at baselines and once a month during treatment. Lumbar spine bone mineral density and biochemical markers of bone metabolism were studied at the beginning and at the end of 3 months. Letrozole significantly decreased uterine leiomyoma sizes (P < 0.01) and promptly benefited women with heavy menstrual bleeding associated with leiomyomas without changing bone mineral density. Aromatase inhibitors may represent a new generation of medications for the treatment of leiomyoma and associated symptoms. Larger clinical trials are needed, however, to fully evaluate their safety and efficacy.
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PMID:Treatment of symptomatic uterine leiomyoma with letrozole. 1885 13

Experimental animal studies have demonstrated that exposure to some phthalates may be associated with altered endocrine function and adverse effects on male reproductive development and function, but human studies are limited. In the present study, urine and serum samples were collected from 425 men recruited through a US infertility clinic. Urinary concentrations of mono(2-ethylhexyl) phthalate (MEHP), the hydrolytic metabolite of di(2-ethylhexyl) phthalate (DEHP), and other phthalate monoester metabolites were measured, along with serum levels of testosterone, estradiol, sex hormone-binding globulin (SHBG), follicle-stimulating hormone, luteinizing hormone, inhibin B, and prolactin. Two oxidized urinary metabolites of DEHP were also measured in urine from 221 of the men. In multiple regression models adjusted for potential confounders, MEHP was inversely associated with testosterone, estradiol, and free androgen index (FAI). An interquartile range increase in MEHP was associated with 3.7% (95% confidence interval [CI], -6.8% to -0.5%) and 6.8% (95% CI, -11.2% to -2.4%) declines in testosterone and estradiol, respectively, relative to the population median hormone levels. There was limited evidence for effect modification of the inverse association between MEHP and FAI by the proportion of DEHP metabolites in the urine measured as MEHP (MEHP%), which is considered a phenotypic marker of less efficient metabolism of DEHP to its oxidized metabolites. Finally, the ratio of testosterone to estradiol was positively associated with MEHP (P = .07) and MEHP% (P = .007), suggesting potential relationships with aromatase suppression. In conclusion, these results suggest that urinary metabolites of DEHP are inversely associated with circulating steroid hormone levels in adult men. However, additional research is needed to confirm these findings.
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PMID:Urinary metabolites of di(2-ethylhexyl) phthalate are associated with decreased steroid hormone levels in adult men. 1905 3

Endometriosis is so far considered as an incurable inflammatory disease. The ectopical implants of endometrial cells proliferate, increase in size and thereafter bleed following the menstrual cycle. The accumulated blood aggravates the situation by developing into cysts which, depending on the place, size and number, in most cases increase pain. Infertility in endometriosis is related either to mechanical distortion of the reproductive truck or to various endometriosis-induced factors including hormones, cytokines and chemokines. Except from the anti-inflammatory treatments and gonadotropin-releasing hormone agonists that have been used for a long time to relief from pain, new treatments are targeted against either hormonal-mediated cell growth via inhibition of the metabolic pathway of estrogens and androgens or vascularization or even implantation of the endometrial engraftment. Thus, the role of selective estrogen, androgen or progesterone receptor modulators, aromatase inhibitors, vascular endothelial growth factor receptor and extracellular matrix modulators is reviewed. This article also reviewed recent patents related to the field.
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PMID:Recent knowledge and new pharmaceutical products in potential alleviation of endometriosis. 1907 2

Endometriosis is a common, benign and chronic gynecological disorder. It is also an estrogen-dependent disorder that can result in substantial morbidity, including pelvic pain, pro gressive dysmenorrhea, dyspareunia, infertility and repeat surgeries. Endometriosis is often treated surgically upon diag nosis but with a higher rate of recurrence, suggesting that a combination of surgical and medical management might provide better outcomes. The primary goal of medical treatment for endometriosis is to halt the growth and activity of endometriosis lesions. The most widely utilized medical treat ment for endometriosis involves use of gonadotropin-releasing hormone (GnRH) agonists and oral contraceptives. Conventional agents also include androgen derivates and progestins. Due to the chronic nature of this disease, long-term or Dr. Hong-Yuan Huang repeated courses of medication may be required to control its related symptoms. Increasing knowledge about the pathogenesis of endometriosis at the cellular and molecular levels may give us the opportunity to use new, specific agents for treatment, including aromatase inhibitors, progesterone antagonists, selective progesterone receptor modulators, GnRH antagonists, intrauterine releasing systems with progestin and new pharmaceutical agents affecting inflammation, angiogenesis, and matrix metalloproteinase activity. Many of these promising new agents may prevent or inhibit the development of endometriosis. Further clinical trials may determine if these new therapies are superior to current medical treatment strategies for endometriosis.
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PMID:Medical treatment of endometriosis. 1909 89

Endometriosis is a common and chronic disease characterized by persistent pelvic pain and infertility. Estradiol is essential for growth and inflammation in endometriotic tissue. The complete cascade of steroidogenic proteins/enzymes including aromatase is present in endometriosis leading to de novo estradiol synthesis. PGE(2) induces the expression of the genes that encode these enzymes. Upon PGE(2) treatment, coordinate recruitment of the nuclear receptor SF-1 to the promoters of these steroidogenic genes is the key event for estradiol synthesis. SF-1 is the key factor determining that an endometriotic cell will respond to PGE(2) by increased estradiol formation. The presence of SF-1 in endometriosis and its absence in endometrium is determined primarily by the methylation of its promoter. The key steroidogenic enzyme in endometriosis is aromatase encoded by a single gene because its inhibition blocks all estradiol biosynthesis. Aromatase inhibitors diminish endometriotic implants and associated pain refractory to existing treatments in affected women.
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PMID:Steroidogenic factor-1 and endometriosis. 1915 Apr 83

Deteriorated male reproductive health has been connected to overexposure to estrogens or to imbalanced androgen-estrogen ratio. Transgenic male mice expressing human aromatase (AROM(+) mice) serve as an apt model for the study of the consequences of an altered androgen-estrogen ratio. Our previous studies with AROM(+) mice showed that low androgen levels together with high estrogen levels result in cryptorchidism and infertility. In the present study, the AROM(+) mice were shown to have severe abnormalities in the structure and function of Leydig cells before the appearance of spermatogenic failure. Decreased expression of adult-type Leydig cell markers (Ptgds, Vcam1, Insl3, Klk21, -24 and -27, Star, Cyp17a1, and Hsd17b3) indicated an immature developmental stage of the Leydig cells, which appears to be the first estrogen-dependent alteration. Genes involved in steroidogenesis (Star, Cyp17a1, and Hsd17b3) were suppressed despite normal LH levels. The low expression level of kallikreins 21, 24, and 27 potentially further inhibited Leydig cell function via remodeling extracellular matrix composition. In connection with disrupted steroidogenesis, Leydig cells showed enlarged mitochondria, a reduced amount of smooth endoplasmic reticulum, and an accumulation of cholesterol and precursors for cholesterol synthesis. The results of studies with AROM(+) mice crossed with estrogen receptor alpha or beta (ERalpha and ERbeta, respectively) knockout mice lead to the conclusion that the structural and functional disorders caused by estrogen exposure were mediated via ERalpha, whereas ERbeta was not involved.
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PMID:Increased exposure to estrogens disturbs maturation, steroidogenesis, and cholesterol homeostasis via estrogen receptor alpha in adult mouse Leydig cells. 1919 1

Endometriosis is an estrogen-dependent disease, causing pelvic pain and infertility. c-fos is an early transcription factor that has been reported to be related to estradiol-dependent cell proliferation. The aim of the present study was to assess the c-fos gene and protein expression in pelvic endometriotic implants in comparison to normal endometrium from infertile women. An open, prospective and controlled study included 15 infertile women with endometriosis and 19 control infertile women. Endometrial and endometriotic biopsies were performed at the follicular phase and the samples were processed for RT-PCR and immunohistochemistry. ERalpha mRNA levels were similar in the endometriotic implants/eutopic endometrium from women with endometriosis and in normal tissue (P = 0.649). The aromatase gene, however, was not expressed in the eutopic endometrium from either control or endometriosis groups, and was only expressed in 50% of endometriotic implants (P = 0.044). c-fos gene expression was higher in endometriotic implants (1.32 +/- 0.13; P = 0.011) than in eutopic endometrium from patients with endometriosis (0.97 +/- 0.11) or from the control group (0.91 +/- 0.05). In addition, immunohistochemistry showed a more abundant distribution of c-Fos in the stroma of endometriotic tissue compared to eutopic endometrium. These data suggest that c-fos may play a role in the molecular mechanisms of estrogen action on the induction, promotion or progression of endometriosis.
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PMID:c-fos gene and protein expression in pelvic endometriosis: a local marker of estrogen action. 1919 93

Endometriosis is an enigmatic, debilitating disease which affects as many as 15% of all women of reproductive age and is characterized by pelvic pain and infertility. Current treatment regimes used to manage the disease do so by inducing a hypoestrogenic state. While the absence of circulating estrogen levels lead to a regression of the disease, this hypoestrogenism also induces many unpleasant side-effects. As such, these and other shortcomings of current drug therapies emphasize their limitations and the necessity for the development of novel endometriosis treatments. In this review, current therapies which target the biochemistry of the implant are discussed with emphasis on aromatase inhibitors, anti-angiogenic compounds and vascular-disrupting agents.
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PMID:Future targets in endometriosis treatment: targeting the endometriotic implant. 1927 25

Aromatase expression in the endometrium seems to play a pivotal role in the development of endometriotic lesions. Because inflammatory mediators such as prostaglandin E2 appear to activate aromatase in the cells of the endometrial stroma, it was hypothesised that the ensuing inflammation caused by the arrival of aromatase-positive cells in the peritoneal cavity would stimulate local estrogen production, which would in turn facilitate the development of endometriotic lesions by suppressing macrophage phagocytosis. Aromatase expression in the eutopic endometrium will also hamper ovum nidation, thus causing infertility. Progestins, such as gestodene and danazol, are potent inhibitors of aromatase expression in the endometrium, and the use of vaginal rings with danazol in doses that do not block ovulation is associated with the occurrence of pregnancy in patients with severe endometriosis without the need for surgery. A local effect on the endometrium suppressing aromatase expression has been suggested as a possible mechanism of action for the danazol ring.
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PMID:Is aromatase expression in the endometrium the cause of endometriosis and related infertility? 1934 Jun 22

Pelvic endometriosis in women is a very common disease. The incidence of this condition in Poland in reproductive age women is about 7-15%, and as much as 50% of cases is diagnosed in patients with co-existing infertility and/or pain and adhesion of a true pelvis. The choice of a therapeutic method depends on the patient's age, stage of the disease, desire for pregnancy, the presence of adhesion, focus localization and a reaction to previous treatment. Currently, the most popular is surgical treatment sometimes followed by pharmacotherapy. Pharmacological treatment includes hormone therapy and symptomatic treatment, also the use of painkillers. Hormonal agents are administered to suppress ovarian activity and cause atrophy of ectopic foci of endometrium. At present, post-surgical pharmacotherapy for endometriosis uses mainly such hormones as: the Combined Oral Contraceptive Pill (COCP), progestagens, danazol, GnRh (gonadotropin-releasing hormone) analogues, aromatase inhibitors and other less common drugs. Also other therapeutic procedures are recommended in endometriosis treatment, procedures which support and in certain clinical situations even replace classical pharmacological methods. Some of them are immunotherapy and a diet rich in isoflavones, organic compounds which modulate estrogen receptor activity. Numerous clinical trials proved that preoperative pharmacotherapy does not improve treatment results and is not applicable to endometriomas in women. On the other hand, postoperative pharmacotherapy still ignites controversy. As maintained by the most recent literature, in the case of mild endometriosis (clinical Stage I and II according to the American Society for Reproductive Medicine) endometrial ablation has better effects than observation only, however postoperative pharmacotherapy does not improve the results of treatment. In more severe cases (clinical Stage III and IV), the best results are achieved by the combined treatment. Nevertheless, no randomized research has been carried out on a wide scale in this group of patients.
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PMID:[Pharmacotherapy for pelvic endometriosis in women]. 1938 39


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