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M Hickey

Publications and source records attributed to M Hickey.

At least 19 recordsLinked to original sources
PubMed2003

Changes in endometrial blood vessels in the endometrium of women with hormone replacement therapy-related irregular bleeding.

BACKGROUND: Irregular bleeding affects up to 60% of hormone replacement therapy (HRT) users. The mechanism of this bleeding is not understood. Reduced endometrial microvascular integrity appears to underlie breakthrough bleeding in pre-menopausal women and the aim of this study was to establish whether similar changes are seen in HRT users and hence to elucidate a possible mechanism of irregular bleeding. METHODS: Endometrium from 34 HRT users with amenorrhoea, irregular bleeding or regular bleeding was assessed for endometrial endothelial cell density (anti-CD34), number of blood vessels per mm(2), vascular basal lamina components (laminin, collagen IV and heparan sulphate proteoglycan) and in 32 subjects and 23 controls for perivascular smooth muscle alpha (SMA). Findings were compared with a control population of 29 post-menopausal women not using HRT, other sex steroids or tamoxifen and with no vaginal bleeding. Staining intensity was assessed in a blinded fashion in all immunohistochemical studies. RESULTS: Four significant differences in endometrial blood vessels were observed between HRT users and controls: (i) a significantly lower density of endometrial endothelial cells (EC staining for CD34) per mm(2) was present in HRT users compared with controls (P < 0.001); (ii) endothelial cells (EC) were predominantly organized within blood vessels (83%) in controls but in HRT users EC were dispersed in the tissues with only 29% in organized vessels (P <0.001); (iii) supportive perivascular cell SMA was significantly reduced in 23 post-menopausal HRT users compared with 23 post-menopausal controls (n = 29, P = 0.013) and (iv) an atrophic or inactive histological pattern of endometrium was more frequently seen in the controls (P < 0.001). CONCLUSIONS: These findings support the hypothesis that exposure to HRT profoundly alters endometrial blood vessels, reducing structural integrity thereby predisposing to irregular bleeding in HRT users.

Actins↗
PubMed2002

Endometrial destruction techniques for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding (HMB) is a significant health problem in premenopausal women that can reduce quality of life and cause anaemia. First line therapy has traditionally been medical therapy but this is not always completely effective. Hysterectomy, often used after the failure of medical therapy, is 100% effective but is risky, costly and can cause complications. Endometrial ablation is less invasive, less costly and preserves the uterus. A large number of techniques have been developed to "ablate" (remove) the lining of the endometrium. The gold standard techniques (laser, transcervical resection of the endometrium and rollerball) require visualisation of the uterus with a hysteroscope and, although safe, require skilled surgeons. A number of newer techniques have recently been developed, most of which can be performed blind and are less time consuming. Many of these techniques are still under development, refinement and investigation. OBJECTIVES: To compare the efficacy, safety and acceptability of methods used to destroy the endometrium to reduce HMB in premenopausal women. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (issue 4, 2001), Medline (1966 to September 2001), EmBase (1980 to August 2001), Current Contents (1993 to week 38, 2001), Biological Abstracts (1980 to June 2001), Psyclit (1967 to August 2001) and Cinahl (1982 to July 2001). We also searched the specialised register of the Cochrane Menstrual Disorders and Subfertility Group (August 2001). We also searched reference lists of articles and contacted pharmaceutical companies and experts in the field. SELECTION CRITERIA: Randomised controlled trials comparing endometrial ablation techniques in women with a complaint of heavy menstrual bleeding without uterine pathology. The outcomes included reduction of heavy menstrual bleeding, improvement in quality of life, operative outcomes, satisfaction with outcome, complications and need for further surgery. DATA COLLECTION AND ANALYSIS: The two reviewers independently selected trials for inclusion, assessed trials for quality and extracted data. Attempts were made to contact authors for clarification of data in some trials. Adverse events were only assessed if they were separately measured in the included trials. MAIN RESULTS: In comparing hysteroscopic techniques, the vaporising electrode procedure was less difficult to perform (OR=0.25, 95%CI 0.1, 0.7) and had less fluid deficit (WMD=-258mls, 95% CI -342.1, -174.0) than TCRE. The odds of fluid overload and equipment failure were higher ((OR=5.2, 95% CI 1.5, 18.4) and (OR=6.0, 95% CI 1.7, 20.9) respectively) for those women having laser as compared to TCRE (transcervical resection of the endometriuim). In comparing traditional hysteroscopic endometrial ablation with the newer 2nd generation techniques overall, the newer techniques took less time to perform (WMD=-11mins, 95% CI -18.6, -2.6) and were more likely to be performed under local anaesthesia (OR=7.6, 95% CI 1.1, 52.7) but had a greater chance of equipment failure (OR=4.1, 95% CI 1.1, 15.0). The reduction in heavy bleeding did not differ significantly between any of the groups. REVIEWER'S CONCLUSIONS: Endometrial ablation techniques continue to play an important role in the management of HMB. The rapid development of a number of new methods of endometrial destruction has made systematic comparisons between methods and with the "gold standard" of TCRE difficult. Most of the newer techniques are performed blind and are technically easier than hysteroscopy-based methods. Overall, the existing evidence suggests success rates and complication profile of newer techniques of ablation compares favourably with TCRE, although technical difficulties with new equipment need to be ironed out.

Adult↗
PubMed2002

Apical barriers to airway epithelial cell gene transfer with amphotropic retroviral vectors.

Gene transfer to airway epithelia with amphotropic pseudotyped retroviral vectors is inefficient following apical vector application. To better understand this inefficiency, we localized the expression of Pit2, the amphotropic receptor, in polarized human airway epithelia. Pit2 was expressed on both the apical and basolateral surfaces of the cells, suggesting that factors other than receptor abundance may limit apical gene transfer efficiency. Binding studies performed with radiolabeled amphotropic MuLV suggested that the apically applied virus binds to Pit2. Hypothetical barriers to retroviral gene transfer include the apical glycocalyx and other secreted products of epithelia. In this study, we demonstrated that sialic acid, keratan sulfate and collagen type V are present on the apical surface of well-differentiated human airway epithelia. While enzyme treatment reduced the abundance of these components, the treatment also decreased the transepithelial resistance to approximately 35% of the controls, suggesting that the epithelial integrity was impaired. To attain an airway epithelial culture with a modified apical surface and intact epithelial integrity, we utilized 100 mM 2-deoxy-D-glucose, a glycosylation inhibitor, to prevent the glycocalyx from reforming following enzyme treatment. This approach allowed the resistance, but not the apical glycocalyx to recover. Despite this physical modification of the cell surface, the amphotropic retroviral vector failed to transduce airway epithelia following apical application. These results suggest that factors other than apical receptor abundance and the glycocalyx inhibit amphotropic retroviral gene transfer in human airway epithelia.

Cell Polarity↗
PubMed2002

Clinical outcomes following percutaneous magnetic resonance image guided laser ablation of symptomatic uterine fibroids.

BACKGROUND: Fibroids are common benign tumours of the uterus. Percutaneous magnetic resonance (MR) image guided laser ablation provides a minimally invasive, day-case alternative to surgery for the treatment of symptomatic fibroids. METHODS: Women with symptomatic fibroids wishing to avoid surgery were treated with laser ablation. MR thermal mapping ensured that maximal safe energy was applied. Fibroid volume was measured at 3 and 12 months, menstrual blood loss was recorded before and after treatment and a menorrhagia outcomes questionnaire (MOQ) was used to assess satisfaction. RESULTS: A total of 66 patients was treated. There was a significant (P < 0.001) reduction in mean fibroid volume of 31%. This was 41% at 1 year follow-up (P < 0.001). Measured menstrual blood loss in eight patients complaining of excessive bleeding was reduced (P = 0.012). The MOQ total outcome score was not as good as that seen in hysterectomy patients (P = 0.02) but the quality of life/satisfaction score was similar (P = 0.06). CONCLUSION: We have used objective and subjective outcome measures to determine the efficacy of MR guided laser ablation for fibroids. Based on this limited study we are encouraged that this procedure may represent a minimally invasive alternative therapy for fibroids.

Female↗
PubMed2002

Endometrial destruction techniques for heavy menstrual bleeding: a Cochrane review.

UNLABELLED: This paper is based on a Cochrane review published in The Cochrane Library, issue 3, 2002 (see www.CochraneLibrary.net for information) with permission from The Cochrane Collaboration and Update Software. Cochrane reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and The Cochrane Library should be consulted for the most recent version of the review. BACKGROUND: The objective of this review was to compare the efficacy, safety and acceptability of methods used to destroy the endometrium to reduce heavy menstrual bleeding (HMB) in premenopausal women. METHODS: We searched the Cochrane Controlled Trials Register, Medline, Embase, Current Contents, Biological Abstracts, Psyclit and CINAHL. We also searched the specialized register of the Cochrane Menstrual Disorders and Subfertility Group and reference lists of articles, and contacted pharmaceutical companies and experts in the field. Randomized controlled trials comparing endometrial ablation techniques in women with a complaint of HMB without uterine pathology were selected. The outcomes included reduction of HMB, improvement in quality of life, operative outcomes, satisfaction with outcome, complications and need for further surgery. The two reviewers independently selected trials for inclusion, assessed trials for quality and extracted data. Attempts were made to contact authors for clarification of data in some trials. Adverse events were only assessed if they were separately measured in the included trials. RESULTS: In comparing hysteroscopic techniques, the vaporizing electrode procedure was less difficult to perform [odds ratio (OR) = 0.25; 95% confidence interval (CI): 0.1, 0.7] and had less fluid deficit [weighted mean difference (WMD) = -258 ml; 95% CI: -342.1, -174.0] than transcervical resection of the endometrium (TCRE). The odds of fluid overload and equipment failure were higher (OR = 5.2; 95% CI: 1.5, 18.4 and OR = 6.0; 95% CI: 1.7, 20.9 respectively) for those women having laser treatment as compared with TCRE. In comparing traditional hysteroscopic endometrial ablation with the newer second generation techniques overall, the newer techniques took less time to perform (WMD = -11 min; 95% CI: -18.6, -2.6) and were more likely to be performed under local anaesthesia (OR = 7.6; 95% CI: 1.1, 52.7) but had a greater chance of equipment failure (OR = 4.1; 95% CI: 1.1, 15.0). The reduction in HMB did not differ significantly between any of the groups. CONCLUSIONS: The rapid development of a number of new methods of endometrial destruction has made systematic comparisons between methods and with the 'gold standard' of TCRE difficult. Most of the newer techniques are performed blind and are technically easier than hysteroscopy-based methods. Overall, the existing evidence suggests that success rates and complication profile of newer techniques of ablation compare favourably with TCRE, although technical difficulties with new equipment need to be ironed out.

Endometrium↗
PubMed2002

Surface vascularization and endometrial appearance in women with menorrhagia or using levonorgestrel contraceptive implants. Implications for the mechanisms of breakthrough bleeding.

BACKGROUND: Women using progestogen-only contraceptives are commonly troubled by irregular bleeding. Endometrial vessel breakdown and repair is thought to be locally regulated under the indirect influence of sex steroids. Most information about endometrial vessels is derived from blind biopsies taken in an outpatient setting. Hysteroscopy allows in-vivo observation of the whole endometrial surface, including vessel morphology, distribution and areas of bleeding, as well as information about non-vascular structures that may not be accessible from biopsies. METHODS: Hysteroscopies were performed on 34 women using the levonorgestrel contraceptive implant system (Norplant(TM)) and in a comparison group of 20 women complaining of menorrhagia due to ovulatory dysfunctional bleeding. The images were captured and vascular appearances assessed using image analysis. RESULTS: The percentage of the superficial endometrium covered with blood vessels was found to be significantly greater in Norplant users compared with the comparison group (P = 0.0006). More superficial vessels were seen in those with recent frequent or prolonged bleeding and spotting (P < 0.0001). In Norplant users, but not in the comparison group, superficial vascular distribution was predominantly patchy (P < 0.0001). Unusual vascular appearances classified as 'neovascular' (P < 0.0001) and 'mosaic' (P < 0.0001) patterns were commonly seen in Norplant users but not in the comparison group. The hysteroscopic appearance of the endometrial epithelium, glands and stroma also differed between Norplant users and women with menorrhagia. Apparent shedding of the superficial endometrium was commonly seen by hysteroscopy in Norplant users during a bleeding episode (P < 0.0001). Prominent gland openings with thick mucus were commonly seen in Norplant users and small sessile polyps were seen in six cases. CONCLUSIONS: These hysteroscopic observations provide further evidence that exposure to progestogens alters the superficial endometrial vasculature and may interfere with angiogenesis.

Adult↗
PubMed2001

A multicenter, prospective, randomized trial evaluating a new hemostatic agent for spinal surgery.

STUDY DESIGN: A prospective, randomized trial comparing Proceed, a gelatin-based hemostatic sealant (treatment), with Gelfoam-thrombin (control) in stopping intraoperative bleeding during spinal surgery. OBJECTIVES: To determine the effectiveness and safety of Proceed. SUMMARY OF BACKGROUND DATA: Proceed has been tested in animal models to determine its safety and effectiveness as a hemostatic agent. The current study was conducted under a Food and Drug Administration-approved Investigational Device Exemption to evaluate the effectiveness and safety of Proceed in humans. METHODS: For this study, 127 patients undergoing spinal surgery were randomized into either the treatment or control group after standard surgical means to control bleeding had failed. The bleeding site was evaluated at 1, 2, 3, 6, and 10 minutes after the hemostatic agent was applied. The application was considered successful if the bleeding stopped within 10 minutes. Follow-up evaluation was performed at 12 to 36 hours, then at 6 to 8 weeks after surgery. RESULTS: Proceed stopped bleeding in 98% of the patients (first bleeding site only) within 10 minutes, as compared with 90% of the control patients (P = 0.001). At 3 minutes, successful hemostasis had been achieved in 97% of the Proceed group, as compared with 71% of the control group (P = 0.0001). There was no difference in the adverse event profile between the two groups. CONCLUSIONS: A significantly larger number of bleeding sites had achieved hemostasis with Proceed than with Gelfoam-thrombin at 1, 2, and 3 minutes after application. Proceed was as safe as Gelfoam-thrombin when used for hemostasis during spinal surgery procedures.

Administration, Topical↗
PubMed2001

Endometrial bleeding in hormone replacement therapy users: preliminary findings regarding the role of matrix metalloproteinase 9 (MMP-9) and tissue inhibitors of MMPs.

OBJECTIVE: To establish the effect of hormone replacement therapy (HRT) on the expression of matrix metalloproteinase 9 (MMP-9) and the tissue inhibitor of MMPs, TIMP-1, in the endometrium of postmenopausal and perimenopausal women. DESIGN: Prospective observational study. SETTING: United Kingdom teaching hospital. PATIENT(S): Thirty-one perimenopausal and postmenopausal HRT recipients, with a control group of eight postmenopausal women not undergoing HRT. INTERVENTION(S): Prospective record of bleeding patterns and endometrial biopsy. MAIN OUTCOME MEASURE(S): Endometrial histology, bleeding patterns, MMP-9, and TIMP-1 expression. RESULT(S): MMP-9 and TIMP-1 are expressed in benign postmenopausal endometrium. Expression of both molecules is reduced in HRT recipients compared with non-HRT recipients. CONCLUSION(S): Exposure to HRT appears to alter endometrial expression of MMP-9 and TIMP-1 and also the local balance between these molecules. This alteration may promote breakdown of the endometrial extracellular matrix and blood vessels and hence bleeding.

Base Sequence↗
PubMed2000

Abnormalities in muscle function during gait in relation to the level of lumbar disc herniation.

STUDY DESIGN: A comparison between gait in patients undergoing surgery for L4 and L5 lumbar disc herniations and that in an age- and weight-matched control group. OBJECTIVES: To study whether changes in the moments produced at the ankle and knee joints during walking reflect the neurologic level of a herniated nucleus pulposus. SUMMARY OF BACKGROUND DATA: Lumbar herniated discs often cause muscle weakness, reduced motor function, and change in walking capacity. The specific effects of a disc herniation on muscle function during gait is poorly documented. METHODS: Conventional physical examination and kinetic analysis of gait were performed on 16 patients who subsequently underwent surgery for herniated discs (eight with L4-L5 and eight with L5-S1 disc herniations) and 16 healthy control subjects. The three components of the external moment at the ankle and knee were computed. The peak magnitudes of specific components of the external moments were compared with those of the control group. RESULTS: Reduced external ankle plantar flexion moment, indicating a decreased function of the ankle dorsiflexors, was found in patients with herniated nucleus pulposus of both L4-L5 and L5-S1. Reduced external ankle dorsiflexion moment, indicating a decreased function of the ankle plantar flexors, was found only in patients with a lesion to the L5-S1 disc, but not in those with herniations at L4-L5. CONCLUSIONS: Preoperative gait analysis identified functional deficits of the muscles about the ankle and foot that relate to the level of the herniation. Kinetic measurements can assist in understanding the functional limitations associated with specific levels of a herniation.

Adult↗
PubMed2000

Progestogens versus oestrogens and progestogens for irregular uterine bleeding associated with anovulation.

BACKGROUND: Dysfunctional uterine bleeding (DUB) is "excessively heavy, prolonged or frequent bleeding of uterine origin which is not due to pregnancy or to recognizable pelvic or systemic disease". Anovulation may be inferred from a number of observations but in the normal clinical situation, anovulation is often assumed when a woman presents with heavy, prolonged or frequent bleeding, particularly in those at the extremes of reproductive life and in women known to have the polycystic ovarian syndrome. Menstrual bleeding that is irregular or excessive is usually poorly tolerated by the majority of women. Changes in the length of the menstrual cycle generally imply disturbances of the hypothalamo-pituitary-ovarian (HPO) axis. In anovulatory DUB with acyclic (irregular) oestrogen production there will be no progesterone withdrawal from oestrogen primed endometrium and so cycles are irregular. Prolonged oestrogen stimulation may cause a build up of endometrium with erratic bleeding as it breaks down and is expelled. This is the rationale for using cyclical progestogens during the second half of the menstrual cycle in order to provoke a regular withdrawal bleed. Continuous progestogen is intended to induce endometrial atrophy and hence to prevent oestrogen-stimulated endometrial proliferation. Progestogens, and oestrogens and progestogens in combination are already widely used in the management of irregular or excessive bleeding due to DUB, but the regime, dose and type of progestogen used varies widely with little consensus about the optimum treatment approach. OBJECTIVES: To determine the effectiveness and acceptability of progestogens alone, and oestrogens and progestogens in combination in the management of irregular bleeding associated with anovulation. SEARCH STRATEGY: The search strategy of the Menstrual Disorders Group was used to identify all randomised trials of progestogens alone or in combination with oestrogens in the management of irregular menstrual bleeding associated with anovulation. In addition a search of the Cochrane Controlled Trials Register was undertaken. SELECTION CRITERIA: All randomised controlled trials of progestogens (via any route) alone or in combination with oestrogens in the treatment of irregular bleeding associated with anovulation. DATA COLLECTION AND ANALYSIS: Study quality assessment and data extraction were carried out independently by two reviewers. Both reviewers were experts in the content matter. MAIN RESULTS: No randomised trials were identified which compared progestogens with oestrogens and progestogens in the management of irregular bleeding associated with anovulation. Only one small, non-randomised study compared two progestogen regimes in the management of heavy and irregular bleeding in subjects with confirmed anovulation. One randomised study compared the effects of two progestogens on endometrial histology in subjects with a variety of menstrual symptoms, half of whom had cystic glandular hyperplasia. No studies were found which compared progestogens with oestrogens and progestogens in combination or with placebo in the management of irregular bleeding associated with anovulation. REVIEWER'S CONCLUSIONS: There is a paucity of randomised studies relating to the use of progestogens and of oestrogens and progestogens in combination in the treatment of irregular bleeding associated with anovulation. Further research is needed to establish the role of these treatments in the management of this common gynaecological problem.

Adult↗
PubMed2000

Aerobic training in a patient with nonsevere aplastic anemia: a case report.

This case report examined whether a 26-year-old man with a 5-year history of nonsevere aplastic anemia could perform aerobic training and whether exercise was beneficial. Testing was performed at baseline and at 8 and 16 weeks and included complete blood tests, graded exercise tests with breath-by-breath gas analyses, and health status assessment with the Medical Outcomes Survey SF-12 health survey. Training consisted of treadmill walking for 25 minutes, 3 days a week for 16 weeks, at 75% of maximal heart rate. The patient successfully completed 16 weeks of training and had no adverse effects from testing or training. Training did not produce changes in disease-related measures (hematologic values) or impairment measures (cardiopulmonary measures of fitness). The mental component of the SF-12 improved from below 2 standard deviations from the population mean to within 1 standard deviation of the population mean. The benefits of aerobic training for this person with aplastic anemia were that he showed that he could participate in aerobic-type activities and that training appeared to improve his mental health.

Adult↗
PubMed2000

Clinical implications of disturbances of uterine vascular morphology and function.

Menstrual disturbances are one of the most common problems presenting to the gynaecologist. In order for the endometrium to bleed, vessels must break down. Disruption in the regulation of endometrial vascular growth and function has been found in association with spontaneous and sex steroid-induced disturbances of menstrual bleeding. Although circulating oestrogens and progestogens influence the endometrial vessels, this effect appears to be indirect, and regulation is primarily via local factors. Deficient vasoconstriction and haemostasis with excessive fibrinolysis is seen in menorrhagia. Breakthrough bleeding in users of progestogen-only contraceptives is associated with increased superficial vascular fragility and disruptions in the supporting basement membrane. Blood vessels in uterine fibroids are abnormal in distribution and appearance. Adenomyosis is also commonly associated with menstrual disturbance, and alterations in vascular distribution suggest altered angiogenesis. Successful human embryo implantation requires endometrial vascular breakdown. Excessive thrombosis associated with the antiphospholipid syndrome may interfere with this re-modelling and compromise implantation. Arteriovenous malformations are a rare but important cause of excessive or irregular vaginal bleeding. Abundant vessels with abnormal morphology, associated with aberrant angiogenesis can be seen, and embolization of these vessels may be an effective conservative treatment. Improved understanding of the regulation of the uterine vasculature is likely to lead to targeted therapies to prevent unscheduled vascular breakdown and to control menstrual disturbance at an endometrial level.

Arteriovenous Malformations↗
PubMed2000

The measurement of endometrial perfusion in norplant users: a pilot study.

The use of progestogens without oestrogen is commonly associated with irregular menstrual bleeding. Oestrogens and progestogens are both thought to influence endometrial perfusion; changes in endometrial perfusion may contribute to vascular fragility and breakdown. In this study, endometrial perfusion was measured using laser-Doppler fluxmetry in women in the secretory phase of the menstrual cycle before and 4-6 weeks after insertion of the low-dose long-acting levonorgestrel contraceptive implant system, Norplant. Endometrial perfusion was also measured in women exposed to Norplant for up to 19 months. There was no significant difference between endometrial perfusion in control cycles (27.2 flux units +/- 5.5, SEM) and at 4-6 weeks after Norplant insertion (16.3 flux units +/- 5.0), a time when irregular bleeding and spotting are common. Endometrial perfusion was no different from controls after longer periods of Norplant exposure (35.7 flux units +/- 7.2). No direct relationships between endometrial perfusion and plasma concentrations of ovarian steroid hormones were demonstrated. Short-term endometrial vasomotion was largely abolished during Norplant exposure.

Adult↗
PubMed2000

Superficial endometrial vascular fragility in Norplant users and in women with ovulatory dysfunctional uterine bleeding.

The aim of this study was to develop an objective test for superficial endometrial vascular fragility at hysteroscopy, and to apply this test to women using Norplant((R)) for contraception and to women with ovulatory dysfunctional uterine bleeding (DUB). A prospective observational study was carried out in 34 Norplant users and 20 women with menorrhagia due to ovulatory DUB. Superficial endometrial vascular fragility was assessed at hysteroscopy by observing the source and extent of frank and subepithelial bleeding during controlled collapse and redistension of the uterine cavity. Superficial endometrial blood vessels were more fragile in Norplant users compared to women with DUB (chi(2) = 11.60, P = 0.02). Superficial endometrial petechiae (chi(2) = 37.9, P < 0.0001) and ecchymoses (chi(2) = 42.2, P = 0.0001) were more frequently observed in the Norplant users than in the menorrhagia group. In Norplant users, superficial endometrial vascular fragility was increased in those with frequent bleeding or spotting during the past 30 days (chi(2) = 6.15, P = 0.01), and in those who were examined during a bleeding episode (chi(2) = 5.3, P = 0.02). Fragility was increased in the menorrhagia group during the perimenstrual period (days 24 to 05; chi(2) = 12.83, P = 0.01). There was no obvious relationship between subepithelial bleeding and circulating concentrations of oestradiol and progesterone.

Adult↗
PubMed2000

A functional model for progestogen-induced breakthrough bleeding.

During the past 5 years, a number of important advances have been made in our understanding of the mechanisms of sex steroid-induced breakthrough bleeding (BTB). These observations suggest that superficial endometrial vascular fragility may be the mechanism underlying BTB, and molecular changes in the microvasculature as well as hysteroscopic observations have supported this hypothesis. This paper aims to present a unified picture of our current understanding of BTB, particularly that associated with progestogens, to indicate current gaps in our knowledge and possible directions for future research.

Endometrium↗
PubMed2000

The structure of endometrial microvessels.

Recent studies have provided substantial evidence to highlight abnormalities in the structure of endometrial microvessels in users of progestogen-only contraception. Structural changes alone are unlikely to lead to breakthrough bleeding, but appear to be associated with a reduction in vessel integrity, and may reflect alterations in the control and growth of endometrial microvessels in those exposed to exogenous progestogens. In users of low-dose progestogens, immunohistochemical studies have demonstrated changes in superficial endometrial vascular morphology, density and in endometrial migratory cell populations. In Norplant users the endometrial endothelial basal lamina is deficient in the initial months of exposure, when bleeding problems are most common. The basal lamina refers to the very thin structure consisting mostly of collagen IV and laminin seen underlying endothelial and epithelial cells at the electron microscope level. In addition, hysteroscopic studies have demonstrated increased fragility of superficial vessels. Changes in endometrial microvascular anatomy associated with normal menstruation have been reviewed, and are compared with those seen following contraceptive steroid exposure. Likely mechanisms of breakthrough bleeding such as increased superficial vascular fragility and the possible alterations in endometrial vascular structure leading to this are discussed.

Endometrium↗
PubMed2000

Disturbances of endometrial bleeding with hormone replacement therapy.

Breakthrough bleeding is a common problem in postmenopausal women taking hormone replacement therapy (HRT) and is often the single most important factor deterring women from continuing to use HRT, or from starting it in the first place. The mechanisms which underlie this unscheduled bleeding are poorly understood. The benefits of HRT in terms of longevity and quality of life are becoming increasingly apparent, and a greater understanding of why this bleeding occurs and how we can prevent or treat it, will undoubtedly enable more women to reap the potential considerable benefits of long-term oestrogen and progestogen replacement. What sets postmenopausal women apart from their counterparts in the mid-reproductive years is the increased likelihood of endometrial adenocarcinoma in which unscheduled bleeding is the presenting symptom. Therefore, spontaneous postmenopausal bleeding must always be appropriately evaluated. Hence, the occurrence of unscheduled bleeding with HRT may provide a dilemma with diagnosis as well as a challenge to acceptability. Combined HRT regimens tend to be predominantly progestogenic, and there is increasing evidence to suggest that some of the vascular changes seen in women taking long-term, low-dose progestogen-only contraceptives may also occur in women taking HRT.

Adenocarcinoma↗