Reduction In Menstrual Blood Loss Research Articles

Benefit-Risk Assessment of the Levonorgestrel Intrauterine System in Contraception

The levonorgestrel-releasing intrauterine system (IUS) is a long-acting, fully reversible method of contraception. It is one of the most effective forms of contraception available, and combines the advantages of both hormonal and intrauterine contraception. The levonorgestrel-releasing IUS also gives the users many non-contraceptive benefits: the amount of menstrual bleeding and the number of days of menstrual bleeding are reduced, which makes it suitable for the treatment of menorrhagia (heavy menstrual blood loss). Dysmenorrhoea (painful menstruation) and premenstrual symptoms are also relieved. In addition, the levonorgestrel-releasing IUS provides protection for the endometrium during hormone replacement therapy. The local release of levonorgestrel into the uterine cavity results in a strong uniform suppression of the endometrial epithelium as the epithelium becomes insensitive to estradiol released from the ovaries. This accounts for the reduction in menstrual blood loss. All possible patterns of bleeding are seen among users of the levonorgestrel-releasing IUS; however, most of the women who experience total amenorrhoea continue to ovulate. The first months of use are often characterised by irregular, scanty bleeding, which in most cases resolves spontaneously. The menstrual pattern and fertility return to normal soon after the levonorgestrel-releasing IUS is removed. The contraceptive efficacy is high with 5-year failure rates of 0.5-1.1 per 100 users. The absolute number of ectopic pregnancies is low, as is the rate per 1000 users. The levonorgestrel-releasing IUS is equally effective in all age groups and the bodyweight of the user is not associated with failure of the method. In Western cultures continuance rates among users of the levonorgestrel-releasing IUS are comparable with those of other long-term methods of contraception. Premature removal of the device is most often associated with heavy menstrual bleeding and pain, as with other long-term methods of contraception, and is most common in the youngest age group. When adequately counselled about the benign nature of oligo- or amenorrhoea, most women are very willing to accept life without menstruation. The risk of premature removal can be markedly diminished with good pre-insertion counselling, which also markedly increases user satisfaction. User satisfaction is strongly associated with the information given at the time of the levonorgestrel-releasing IUS insertion. Thus, the benefits of the levonorgestrel-releasing IUS make it a very suitable method of contraception for most women.

Use of a levonorgestrel-releasing intrauterine system to treat bleeding related to uterine leiomyomas

Objective This study was designed to evaluate the potential usefulness of the levonorgestrel-releasing intrauterine system (LNG IUS) in treating women with uterine leiomyomas. Design Prospective before-and-after study. Setting Family planning unit in an academic research institute. Patient(s) Sixty-seven women with uterine leiomyomas who chose the LNG IUS as their method of contraception. Intervention(s) Clinical and ultrasound examinations were performed prior to and 3, 6, and 12 months after the LNG IUS insertion. Main outcome measure(s) Menstrual blood loss assessed with pictorial blood loss assessment charts, ferritin and hemoglobin concentrations, and uterine and leiomyoma volume. Result(s) Use of the LNG IUS was associated with a marked reduction in menstrual blood loss. After 12 months of use, the mean pictorial blood loss assessment chart score declined from 97 to 16 ( P<.001). Hemoglobin and ferritin levels increased significantly over 1 year of use. Eighteen of 19 women (95%) who were anemic at the beginning of the study were no longer anemic at 12 months, as judged by hemoglobin levels. No pregnancies occurred during the study. Conclusion(s) The LNG IUS was associated with a profound reduction in menstrual blood loss. For women with leiomyomas of this size, the LNG IUS provides effective medical treatment of bleeding.

A randomised controlled trial comparing the Cavaterm endometrial ablation system with the Nd:YAG laser for the treatment of dysfunctional uterine bleeding

To compare the effectiveness of the Cavaterm thermal balloon endometrial ablation system with the Nd:YAG laser for the treatment of dysfunctional uterine bleeding. Randomised controlled trial. Minimal access gynaecological surgery unit in a district general hospital. Seventy-two women with dysfunctional uterine bleeding requesting conservative surgical management of their condition. Women with a normal endometrial biopsy and normal uterine cavity were randomly allocated to endometrial ablation by Cavaterm or Nd:YAG laser. Patients completed pre-operative and 6- and 12-month post-operative questionnaires assessing menstrual symptoms, quality of life, sexual activity and procedural satisfaction and acceptability. All patients received a single dose of gonadotropin-releasing hormone analogue one month pre-operatively and kept blinded to the procedure performed until after the 6-month assessment. The primary outcome measure was amenorrhoea rate. Secondary outcomes were effect on blood loss, quality of life, sexual activity, patient satisfaction and procedure acceptability. Seventy-two women were randomised. Amenorrhoea rates at 12 months in the Cavaterm and endometrial laser ablation groups were 29% vs 39% (P = 0.286), with combined amenorrhoea and hypomenorrhoea rates of 73% vs 69%, respectively. At 12 months, repeat surgery rates were higher in the endometrial laser ablation group (15% vs 12%, P = 0.395). Cavaterm was an acceptable procedure and 93% of patients satisfied or very satisfied at 12 months (95% endometrial laser ablation). Both treatments were associated with an increase from baseline in the SF-12 physical score (Cavaterm mean difference -3.9, 95% CI -7.9, 0.2, ns; endometrial laser ablation mean difference -5.1, 95% CI -9.5, -0.7, P = 0.003) and mental health score (Cavaterm mean difference -5.6, 95% CI -9.9, -1.3, P = 0.001; endometrial laser ablation mean difference -5.9, 95% CI -11.7, -0.2, P = 0.04). Patient's own assessment of health (EQ-5D VAS) improved from baseline in both groups (Cavaterm mean difference -7.6, 95% CI -13.9, -1.3, P = 0.02; endometrial laser ablation mean difference -5.4, 95% CI -14.9, 4.2, ns). EQ-5D index scores also improved (Cavaterm mean difference -0.06, 95% CI -0.2, 0.005, ns; endometrial laser ablation mean difference -0.17, 95% CI -0.3, -0.02, P = 0.02). There were no major complications in either group. The results with the Cavaterm thermal balloon endometrial ablation system are as good as those obtained with the Nd:YAG laser when used for the treatment of dysfunctional uterine bleeding in the short term. It results in a significant reduction in menstrual blood loss, patient satisfaction and improvement in patient quality of life. Larger studies with longer follow up are required to determine its place in the modern treatment of dysfunctional uterine bleeding.

A randomised controlled trial comparing the Cavaterm endometrial ablation system with the Nd:YAG laser for the treatment of dysfunctional uterine bleeding

Objective To compare the effectiveness of the Cavaterm thermal balloon endometrial ablation system with the Nd:YAG laser for the treatment of dysfunctional uterine bleeding. Design Randomised controlled trial. Setting Minimal access gynaecological surgery unit in a district general hospital. Population Seventy-two women with dysfunctional uterine bleeding requesting conservative surgical management of their condition. Methods Women with a normal endometrial biopsy and normal uterine cavity were randomly allocated to endometrial ablation by Cavaterm or Nd:YAG laser. Patients completed pre-operative and 6- and 12-month post-operative questionnaires assessing menstrual symptoms, quality of life, sexual activity and procedural satisfaction and acceptability. All patients received a single dose of gonadotropin-releasing hormone analogue one month pre-operatively and kept blinded to the procedure performed until after the 6-month assessment. Main outcome measures The primary outcome measure was amenorrhoea rate. Secondary outcomes were effect on blood loss, quality of life, sexual activity, patient satisfaction and procedure acceptability. Results Seventy-two women were randomised. Amenorrhoea rates at 12 months in the Cavaterm and endometrial laser ablation groups were 29% vs 39% ( P = 0.286), with combined amenorrhoea and hypomenorrhoea rates of 73% vs 69%, respectively. At 12 months, repeat surgery rates were higher in the endometrial laser ablation group (15% vs 12%, P = 0.395). Cavaterm was an acceptable procedure and 93% of patients satisfied or very satisfied at 12 months (95% endometrial laser ablation). Both treatments were associated with an increase from baseline in the SF-12 physical score (Cavaterm mean difference −3.9, 95% CI −7.9, 0.2, ns; endometrial laser ablation mean difference −5.1, 95% CI −9.5, −0.7, P = 0.003) and mental health score (Cavaterm mean difference −5.6, 95% CI −9.9, −1.3, P = 0.001; endometrial laser ablation mean difference −5.9, 95% CI −11.7, −0.2, P = 0.04). Patient's own assessment of health (EQ-5D VAS) improved from baseline in both groups (Cavaterm mean difference −7.6, 95% CI −13.9, −1.3, P = 0.02; endometrial laser ablation mean difference −5.4, 95% CI −14.9, 4.2, ns). EQ-5D index scores also improved (Cavaterm mean difference −0.06, 95% CI −0.2, 0.005, ns; endometrial laser ablation mean difference −0.17, 95% CI −0.3, −0.02, P = 0.02). There were no major complications in either group. Conclusions The results with the Cavaterm thermal balloon endometrial ablation system are as good as those obtained with the Nd:YAG laser when used for the treatment of dysfunctional uterine bleeding in the short term. It results in a significant reduction in menstrual blood loss, patient satisfaction and improvement in patient quality of life. Larger studies with longer follow up are required to determine its place in the modern treatment of dysfunctional uterine bleeding.

Therapeutic effects of the levonorgestrel-releasing intrauterine system in the treatment of idiopathic menorrhagia

Objective To investigate the effect of the levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of idiopathic menorrhagia. Design Measurements of menstrual blood loss (MBL), hemoglobin, and serum ferritin before and after LNG-IUS insertion. Setting National Research Institute for Family Planning and Beijing Gynecology and Obstetrics Hospital, Beijing, People’s Republic of China. Patient(s) Thirty-four patients with MBL over 80 mL. Intervention(s) Insertion of the LNG-IUS on cycle days 5–7 and follow-up at 3-month intervals for 3 years. Main outcome measure(s) Measurement of MBL, serum ferritin, and hemoglobin for evaluation of efficacy of treatment. Result(s) A significant reduction of MBL to 23.4 mL (78.7% decrease), 26.4 mL (83.8% decrease), 2.7 mL (97.7% decrease), and 13.7 mL (85.0% decrease) at 6, 12, 24, and 36 months, respectively. After 6 months, one-third of the patients experienced amenorrhea, and one-fourth, spotting. Hemoglobin increased significantly from 121.5 g/L preinsertion to 135.5 g/L after 36 months, while serum ferritin levels increased significantly from 21.9 ng/mL before insertion to 92.8 ng/mL after 36 months. In women using the LNG-IUS for 3–4 years, the E 2 levels in 20 samples were 239.4 pmol/L, P levels were 11.1 nmol/L, and serum LNG levels were maintained at an average of 511 pmol/L. Conclusion(s) The significant reduction of MBL and the increase in hemoglobin and serum ferritin levels in the treatment of menorrhagia with the LNG-IUS has great implications for women’s reproductive health, particularly in developing countries.

Progestin-releasing intrauterine systems.

The levonorgestrel-releasing intrauterine system (LNG IUS) is an effective method for contraception. It has a strong antiproliferative action on the endometrium. The endometrium is transformed under the influence of local levonorgestrel and becomes unresponsive to ovarian estrogens. This process is associated with progressive reduction of menstrual blood loss and menstrual duration. Scanty and irregular bleeding and/or spotting is usual during the first 3 to 4 months. The reduction of menstrual blood loss continues and after the first 9 months many women have no bleeding at all. However, they have normal ovarian function. The absence of bleeding is a result of the local antiproliferative action of the LNG IUS on the endometrium, which is also responsible for many health benefits during the use of this method. As with oral contraceptives, the risk of pelvic inflammatory disease is reduced, because of reduced menstrual blood loss, endometrial suppression, and thickening of the cervical mucus. There are some steroidal side effects: mood changes, oily skin, and acne. Weight increase is similar to that associated with copper intrauterine devices: 500 g per year over 5 years. Users should be told that the LNG IUS does not prevent sexually transmitted infection, and therefore women at risk should also use condoms for their protection.

The levonorgestrel intrauterine system: the benefits of reduced bleeding

The levonorgestrel intrauterine system (LNG-IUS) offers a new therapeutic concept that combines a highly efficient contraceptive with a treatment that reduces menstrual blood loss in both normal women and those with menorrhagia. Initially developed to decrease the risk of expulsion of the intrauterine contraceptive device by reducing myometrial contractility, recent clinical studies have shown that the LNG-IUS provides excellent contraception without many of the adverse effects associated with the conventional intrauterine contraceptive device. The main mechanism of action of the LNG-IUS appears to be at the level of the endometrium, where the high dose of local progestogen causes decidualization, epithelial atrophy and direct vascular changes.Whilst some women experience systemic hormonal effects, circulating concentrations of levonorgestrel are low in comparison to those seen after the levonorgestrel progestogen-only pill. The LNG-IUS results in a dramatic reduction in menstrual blood loss. In turn, this has led researchers to investigate the LNG-IUS as an alternative to surgery for the treatment of dysfunctional uterine bleeding, uterine fibroids and adenomyosis. The system has also been used as a means of delivering progestogen for endometrial protection in postmenopausal hormone replacement regimens.The main side-effect of the LNG-IUS is irregular breakthrough bleeding. This is most common in the first 6 months after insertion. Detailed counselling is crucial to explain this anticipated effect, in order to reduce unnecessary discontinuation of treatment. After 6 months' treatment with the LNG-IUS, 20% of women become amenorrheic, rising to 50% after 5 years. Again, it is important to explain that this is an expected phenomenon, that it is not related to disorders of the hypothalamic-pituitary-ovarian axis, and that this 'bleed-free' status might indeed be viewed as a positive feature in its own right.

The levonorgestrel intrauterine system: therapeutic aspects

Use of the levonorgestrel-releasing intrauterine system (LNG IUS) is associated with a strong reduction in the number of days of bleeding and menstrual blood loss. This effect is based on the marked local action of the intrauterine release of levonorgestrel (LNG) on the endometrium. In suppressed endometrium the production of many highly active compounds ceases. On the other hand, LNG stimulates the synthesis of some regulatory proteins in the endometrium. Reduction of menstrual blood loss results in improvement of the body iron balance and in an increase in hemoglobin concentration. The LNG IUS has been used in the prevention and treatment of iron deficiency anemia. Many studies have demonstrated that the LNG IUS is effective in the treatment of menorrhagia. Reduction of excessive blood loss is seen as soon as the first menstruation after insertion, and at 1 year the reduction is more than 90%. The therapeutic effect is maintained for more than 5 years after first placement of the LNG IUS in the uterine cavity. Correct insertion is essential, and complications and side effects are rare; fertility is preserved, and invasive procedures such as endometrial ablation or hysterectomy and hospitalization are avoided. The third major indication for therapeutic use is in protection of the endometrium in estrogen replacement therapy during peri- and postmenopausal years. A fundal position of the system in the uterine cavity results in reduction of bleeding, and an increasing number of women have no bleeding at all during use of the IUS. Acceptance and continuation of use of the LNG IUS in hormone replacement therapy (HRT) have been high.

Progesterone/progestogen releasing intrauterine systems versus either placebo or any other medication for heavy menstrual bleeding.

Heavy menstrual bleeding (HMB) is an important cause of ill health in women and it accounts for 12% of all gynaecology referrals in the UK. Heavy menstrual bleeding is clinically defined as greater than, or equal to, 80mls blood loss per menstrual cycle but women may complain of excessive bleeding when their blood loss is less than 80ml. Hysterectomy is often used to treat women with this complaint but medical therapy may be a successful alternative. The intrauterine coil device was originally developed as a contraceptive but the addition of uterine relaxing hormones, or progestogens, to these devices resulted in a large reduction in menstrual blood loss. Case studies of 2 types of progesterone/progestogen releasing systems, Progestasert and Mirena, report reductions of up to 90% and dysmenorrhoea may be improved. Insertion, however, may be regarded as invasive by some women affecting its acceptability as a treatment and frequent intermenstrual bleeding and spotting is likely during the first few months. To determine the effectiveness and acceptability of progesterone/progestogen-releasing intrauterine devices in achieving a reduction in heavy menstrual bleeding. All studies which might describe randomised controlled trials of progesterone/progestagen-releasing intrauterine devices for the treatment of heavy menstrual bleeding were obtained by electronic searches of the MEDLINE 1966-1999, EMBASE 1980-1999 databases and the Cochrane Library. Companies producing progestogen releasing intrauterine devices and experts in the field were contacted for information on published and unpublished trials. Randomised controlled trials in women of reproductive age treated with progesterone/progestogen-releasing intrauterine devices versus no treatment, placebo, or other medical or surgical therapy for heavy menstrual bleeding within either the primary care, family planning or specialist clinic setting were eligible for inclusion. Women with postmenopausal bleeding, intermenstrual or irregular bleeding, or pathological causes of heavy menstrual bleeding were excluded. Potential trials were independently assessed by three reviewers and five trials met the criteria for inclusion in the review. The reviewers extracted the data independently and data were pooled where appropriate. Odds ratios for dichtomous outcomes and weighted mean differences for continuous outcomes were estimated from the data. The primary outcome was reduction in menstrual blood loss but incidence of side effects, changes in quality of life and satisfaction and acceptability measures were also assessed. Progesterone/progestogen-releasing intrauterine systems have not been compared to placebo or no treatment. Progestasert has been compared to a number of different medical therapies in one small study but no conclusions can be made about effectiveness. The levonorgestrel-releasing intrauterine device (LNG IUS) has been compared to oral cyclical norethisterone (NET) administered on days 5-26 in one trial and was significantly more effective although there was a large reduction from baseline in both groups and these differences were not perceived by the women undergoing the treatment. Some side effects were more common in the LNG IUS group but a significantly greater proportion of women in this group were satisfied and willing to continue with their treatment. In one trial of women awaiting hysterectomy where the LNG IUS was compared with a control group taking their existing medical therapy, a higher proportion of the women in the former group cancelled their planned surgery after 6 months of treatment. The levonorgestrel-releasing intrauterine device has been compared to a surgical procedure (transcervical resection of the endometrium (TCRE)) in two trials. (ABSTRACT TRUNCATED)

Medical management of dysfunctional uterine bleeding

Complaints of excessive menstrual bleeding (menorrhagia) have a substantial impact on gynaecological services and in most cases no organic pathology is identified. Up to 50% of women who present with menorrhagia have blood losses within the normal range. Medical therapy is indicated for patients who do not wish surgery, or for whom surgery is unsuitable. Non-steroidal anti-inflammatory drugs and tranexamic acid offer a simple therapy to be taken during menses, with reductions in menstrual blood loss (MBL) of 25–35% and 50% respectively. Danazol and the gonadatrophin-releasing hormone analogues are highly effective, but their side-effects make them suitable only for short-term use. The combined oral contraceptive pill and the levonorgestrel intrauterine system give reductions in MBL of 50% and 80%, with additional contraceptive cover. Cyclical progestogens are the most commonly prescribed therapy in the United Kingdom but they are ineffective for the management of ovulatory menorrhagia unless taken at high doses (10–15 mg daily) for 3 weeks out of 4.

Cyclical progestogens for heavy menstrual bleeding.

Excessively heavy menstrual bleeding (HMB) or menorrhagia is an important cause of ill health in women. Eighty per cent of women treated for HMB have no anatomical pathology and so medical therapy, with the avoidance of possibly unnecessary surgery, is an attractive alternative. Of the wide variety of medications used to reduce heavy menstrual bleeding, oral progestogens are the most commonly prescribed in many western countries, although there is little objective evidence to support their use, especially in women with ovulatory menstruation. This review assesses the effectiveness of 2 different regimens of oral progestogens in reducing ovulatory HMB. The primary objective of this review is to investigate the effectiveness of oral progestogen therapy taken either during the luteal phase or for a longer course of 21 days in achieving a reduction in menstrual blood loss in women of reproductive years with heavy menstrual bleeding (HMB). Electronic searches for relevant randomised controlled trials of the Cochrane Menstrual Disorders and Subfertility Group Register of Trials, MEDLINE, EMBASE, PsychLIT, Current Contents, Biological Abstracts, Social Sciences Index and CINAHL were performed. Attempts were also made to identify trials from citation lists of review articles. In most cases, the first author of each included trial was contacted. The inclusion criteria were randomised comparisons of oral progestogen therapy versus placebo or other medical treatments in women of reproductive years with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic causes for their heavy menstrual blood loss. Seven randomised controlled trials (RCTs) were identified that fulfilled the inclusion criteria for this review. The reviewers extracted the data independently and odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data. No RCTs comparing progestogen treatment with placebo were identified. Comparisons between oral progestogens and other medical therapies were assessed separately according to dosage regimen, progestogens given during the luteal phase of the menstrual cycle and progestogens given for 21 days between day 5 and 26. Progestogen therapy during the luteal phase was significantly less effective at reducing menstrual blood loss when compared with tranexamic acid, danazol and the progesterone releasing intrauterine system (IUS) and there was also a strong non-significant trend in favour of nonsteroidal anti-inflammatory drugs (NSAIDs). Duration of menstruation was significantly longer with the progesterone IUS when compared with oral progestogen therapy but significantly shorter under danazol treatment. Compliance and acceptability of treatment where measured did not differ between treatments. Adverse events were significantly more likely under danazol when compared with progestogen treatment. Change in quality of life was not significantly different with progestogen and tranexamic acid therapy but there was a non-significant trend in favour of tranexamic acid for all three categories. Progestogen therapy administered from day 5 to 26 of the menstrual cycle was significantly less effective at reducing menstrual blood loss than the progestogen releasing intrauterine system (LNG IUS) although the reduction from baseline was significant for both groups. The odds of the menstrual period becoming "normal" (ie <80mls/cycle) were also less likely in patients treated with norethisterone (NET) (days 5 to 26) compared to patients treated with LNG IUS. A significantly higher proportion of NET patients found their treatment unacceptable compared to LNG IUS patients. However, the adverse events breast tenderness and intermenstrual bleeding were more likely in the patients with the IUS. (ABSTRACT TRUNCATED)

Nonsteroidal anti-inflammatory drugs for heavy menstrual bleeding.

Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies are also available. Nonsteroidal anti-inflammatory drugs reduce prostaglandin levels which are elevated in women with excessive menstrual bleeding and also may have a beneficial effect on dysmenorrhoea. The primary objective of this review was to investigate the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) in achieving a reduction in menstrual blood loss in women of reproductive years HMB. Electronic searches for relevant randomised controlled trials of the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, MEDLINE, EMBASE, Current Contents, the Cochrane Library and CINAHL were performed. Attempts were also made to identify trials from citation lists of review articles and drug companies were approached for unpublished data. In most cases, the first author of each included trial was contacted for additional information. An updated search was performed in September and October 2001 but no new eligible trials were identified. The inclusion criteria were randomised comparisons of individual NSAIDs with either each other, placebo or other medical treatments in women with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic (treatment induced) causes for their heavy menstrual blood loss. Sixteen RCTs were identified that fulfilled the inclusion criteria for this review and data were extracted independently. Odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data of nine trials. The results of the remaining seven crossover trials with data unsuitable for pooling were described in the Other Data section. As a group, NSAIDs were more effective than placebo at reducing heavy menstrual bleeding but less effective than either tranexamic acid or danazol. Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs but this did not appear to affect the acceptability of treatment. There were no statistically significant differences between NSAIDs and the other treatments (oral luteal progestogen, ethamsylate, progesterone releasing intra-uterine system (IUS), oral contraceptive pill (OCC)) but most studies were underpowered. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB. NSAIDs reduce HMB when compared with placebo but are less effective than either tranexamic acid or danazol. However, adverse events are more severe with danazol therapy. In the limited number of small studies suitable for evaluation, no significant difference in efficacy was demonstrated between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, OCC or IUS.

Uterine artery blood flow parameters in women with dysfunctional uterine bleeding and uterine fibroids: the effects of tranexamic acid.

The objective of this study was to investigate the effects of tranexamic acid on uterine vascular resistance in women with dysfunctional uterine bleeding and in women with menorrhagia associated with fibroids. A longitudinal, prospective study was carried out in premenopausal women referred to a gynecological outpatient department with a complaint of menorrhagia. We studied 24 women with dysfunctional uterine bleeding (mean age 38.8 years; normal ultrasound examination, hysteroscopy and endometrial biopsy) and 12 women (mean age 42.8 years) with at least one fibroid greater than 2.0 cm on ultrasound examination. None were on any form of oral contraception or other medication which could influence uterine vascular resistance. All women had normal coagulation and thyroid function tests. Transvaginal scanning was performed using an Aloka SSD 650 machine with a 5-MHz probe and pulsed Doppler. Pulsatility index (PI) and resistance index (RI) were measured from the left and right uterine arteries before and during the second month of treatment with tranexamic acid (1 g orally three times a day). Menstrual blood loss was assessed using a validated pictorial blood chart. In women with dysfunctional uterine bleeding, the mean PI and RI fell significantly with treatment (PI 2.20-1.94, p = 0.0001; RI 0.81-0.77, p = 0.003). There was a reduction of approximately 30% in menstrual blood loss with treatment (210.0-137.6 ml, p = 0.0001). In women with uterine fibroids, there was no significant change in either the PI or the RI with treatment and there was no significant reduction in menstrual blood loss. We conclude that tranexamic acid significantly reduces uterine artery vascular resistance in women with dysfunctional uterine bleeding. This effect is unlikely to be a mechanism for the action of tranexamic acid in reducing menstrual blood loss but may have important implications for women taking this treatment in the long term.

A double-blind randomised study comparing danazol and medroxyprogesterone acetate in the management of menorrhagia

A randomised study was undertaken comparing danazol 200 mg daily and medroxyprogesterone acetate 10 mg daily from days 16 to 25 in the management of menorrhagia. Twenty-three women were recruited to the study over a 12-month period. Eighteen subjects were suitable for analysis. Three months' therapy was given and patients were observed for a 3-month period following discontinuation of therapy. Menstrual blood loss was estimated during initial patient assessment and then during each of the 6 months of the study. In the danazol group mean blood loss at all treatment phase months was significantly decreased from baseline. In contrast, blood loss was not reduced significantly in any study month when compared with baseline in the medroxyprogesterone acetate group. During the post-treatment phase the mean blood loss in the danazol group increased to above normal levels but remained significantly lower than baseline, and there was a significant reduction in menstrual blood loss in the medroxyprogesterone acetate group.

Management of abnormal uterine bleeding

Patients treated for dysfunctional uterine bleeding are separated into two groups: those with acute bleeding episodes and those with chronic repetitive bleeding problems. An acute bleeding episode is best controlled with the use of high-dose estrogen. A curettage is indicated for patients with acute bleeding resulting in hypovolemia, and a curettage or hysteroscopically directed biopsies is indicated for women with risk factors for endometrial cancer who have persistent bleeding problems. The management of anovulatory dysfunctional uterine bleeding is determined by the needs of the patient. In the adolescent medroxyprogesterone acetate is administered orally once a day for 10 days each month for ≥3 months, and the patient is monitored closely thereafter. Oral contraceptives are used for women of reproductive age with anovulatory bleeding episodes who also require contraception. Clomiphene citrate is used for women of reproductive age with anovulatory bleeding who want to conceive. Oral medroxyprogesterone acetate is administered 10 days each month for 6 months for the treatment of anovulatory dysfunctional uterine bleeding alone in this age group. For the perimenopausal patient dysfunctional uterine bleeding may be treated by the administration of cyclic progestin or cyclic conjugated equine estrogens for 25 days with the concomitant administration of medroxyprogesterone acetate for days 16 to 25. The perimenopausal patient with dysfunctional uterine bleeding who is a nonsmoker and does not have evidence of vascular disease may also be treated with low-dose combination oral contraceptives. The long-term treatment for women with ovulatory dysfunctional uterine bleeding is the most difficult type of dysfunctional uterine bleeding to manage. The long-term therapy is directed at the reduction in menstrual blood loss. For these patients prolonged progestin use, oral contraceptives, nonsteroidal antiinflammatory drugs, antifibrinolytic agents, danazol, and as a last resort gonadotropin-releasing hormone agonists are part of the therapeutic armamentarium. A combination of two or more of these agents is often required to successfully control the abnormal bleeding. For patients who no longer desire future fertility and have associated pelvic pathologic disorders or for those who fail all medical regimens, surgical therapy may be considered. Either hysterectomy or endometrial ablation has been used. Patients with von Willebrand's disease and excessive menstrual blood loss may be misdiagnosed as having dysfunctional uterine bleeding. von Willebrand's disease is the most common bleeding disorder and is present in approximately 1% of the population. It is much more common than previously recognized. There are improved diagnostic tests to identify this disorder and, most important, there is a high-concentration desmopressin acetate nasal spray available as treatment that does not involve the risk of transmission of hepatitis and human immunodeficiency virus. (Am J Obstet Gynecol 1996;175:787-92.)

Levonorgestrel intrauterine device in the treatment of menorrhagia in chinese women: Efficacy versus acceptability

Ten Chinese women who had menorrhagia without organic cause and suffered from anaemia were treated with levonorgestrel intrauterine device for a total of 129 woman-months. There was a 54%, 87% and 95% reduction in menstrual blood loss at the first, third and sixth month of treatment when compared with the pretreatment cycle. These percentages of reduction were statistically significant, with p values of 0.004, 0.03 and 0.008, respectively. There was a median increase in menstrual cycle length of 12 days in nine months. Fifteen percent of the menstrual cycles were longer than 60 days. The total bleeding days increased by 4 days at the third menstrual cycles, but reduced to a median of 6 days at 6 months. Seventy-six percent of the menstrual bleeding was in the form of spotting. These Chinese women accepted such menstrual alterations. There was no hormonal side effects. All women preferred the device to hysterectomy. Levonorgestrel intrauterine device appeared to be an effective and acceptable treatment for menorrhagia in perimenopausal Chinese women.

Levonorgestrel-releasing and copper-releasing (Nova T) IUDs during five years of use: A randomized comparative trial

A 20 micrograms/24 hours levonorgestrel-releasing intrauterine contraceptive device (LNG-IUD) has, in an open randomized multicenter study, been compared to the copper-releasing device Nova T during 5 years of use; 1821 women had the LNG-IUD and 937 women had the Nova T inserted. The 5-year cumulative gross pregnancy rate was 5.9 % for Nova T and 0.5% for the LNG-IUD. The local effect of levonorgestrel in the uterine cavity causes reduction of menstrual blood loss and development of oligo-amenorrhea, and the termination rates because of heavy and/or prolonged menstrual flow were significantly ( P < 0.001) lower among LNG-IUD users. However, the gross termination rate because of amenorrhea was 6.0 in this group. Hb increased during use of the LNG-IUD and decreased during Nova T use, and the difference between the devices was statistically significant. The incidence of pelvic inflammatory disease (PID) was low in LNG-IUD users regardless of age, whereas in the Nova T group, the PID rate was increased among the youngest women, which makes the difference between the devices significant ( P < 0.01). The gross termination rate for reasons considered to be hormonal was 12.1 in the LNG-IUD group compared to 2.0 in the Nova T group ( P < 0.001). The LNG-IUD is a long-acting reversible contraceptive method for 5 years with a pregnancy rate comparable to female sterilization. The incidence of PID is low even in young women. In addition, the positive health effects such as decreased menstrual blood loss and increased blood haemoglobin concentration make the LNG-IUD a favorable combination of hormonal and intrauterine contraception.

The influence of a low-dose combined oral contraceptive on menstrual blood loss and iron status

The influence of a low-dose combined oral contraceptive (ethinyl estradiol 30 μg + desogestrel 0.15 mg) on menstrual blood loss (MBL) was evaluated in 20 healthy, young women. MBL prior to commencing oral contraception was 60.2 ± 5.6 ml (range 22–116 ml), and decreased (p < 0.001) to 36.5 ± 5.2 ml (range 7–80 ml) and 33.7 ± 4.1 ml (range 5–70 ml) after 3 and 6 months' oral contraceptive medication, respectively. The reduction in MBL during oral contraception was most apparent during the first two days of menstruation. Five women had an MBL > 80 ml prior to commencing oral contraceptive medication. In all of these women, MBL during the 6th menstrual period after commencing oral contraception was < 80 ml. All the women included in this study had a normal blood hemoglobin concentration, hematocrit and erythrocyte indices and there were no significant changes in these variables during the course of the study. Serum ferritin concentration prior to commencing oral contraception was 44.2 ± 9.0 μg/l and was largely unchanged after 6 months' oral contraception (39.7 ± 6.3 μg/l). On admission to the study, two women had a serum ferritin < 10 μg/l, indicative of low iron stores. Both these women had an MBL > 80 ml at the baseline assessment. Serum ferritin concentration increased during oral contraceptive medication in both women (from 8.5 μg/l to 12.0 μg/l and from 5.4 μg/l to 6.8 μg/l, respectively).The duration of menstruation (p < 0.01) and the number of women suffering from dysmenorrhea (p < 0.05) was reduced during oral contraception.

A comparison of flurbiprofen, tranexamic acid, and a levonorgestrel-releasing intrauterine contraceptive device in the treatment of idiopathic menorrhagia

Treatment with flurbiprofen (100 mg twice a day for 5 days), tranexamic acid (1.5 gm three times a day for 3 days and 1 gm twice a day for another 2 days), and an intrauterine contraceptive device releasing 20 micrograms levonorgestrel per day was compared in women with idiopathic menorrhagia. The menstrual blood loss during two control periods in 15 women subsequently treated with flurbiprofen and tranexamic acid was 295 +/- 52 ml and 203 +/- 25.2 ml in the 16 women later fitted with a levonorgestrel-releasing intrauterine contraceptive device. Menstrual blood loss was reduced by all three forms of treatment. The reduction in menstrual blood loss expressed as a percentage of the mean of two control cycles for each form of treatment was as follows: flurbiprofen, 20.7% +/- 9.9%; tranexamic acid, 44.4% +/- 8.3%; levonorgestrel-releasing intrauterine contraceptive device after 3 months, 81.6% +/- 4.5%; levonorgestrel-releasing intrauterine contraceptive device after 6 months, 88.0% +/- 3.1%; levonorgestrel-releasing intrauterine contraceptive device after 12 months, 95.8% +/- 1.2%. The reduction in menstrual blood loss achieved by the levonorgestrel-releasing intrauterine contraceptive device was greater than that recorded with flurbiprofen (p less than 0.001) and tranexamic acid (p less than 0.01), and was greater for tranexamic acid when compared with flurbiprofen (p less than 0.05). The levonorgestrel-releasing intrauterine contraceptive device was the only form of treatment to reduce mean menstrual blood loss below 80 ml per menstruation, the upper limit of normal menstrual blood loss.

Gestrinone in the treatment of menorrhagia

The role of gestrinone, 2.5 mg twice weekly, in treating proven menorrhagia (greater than 80 ml) was examined in 19 women. They were treated for five cycles (2 placebo, 3 active), taking one capsule twice weekly. Placebo had no effect on menstrual blood loss (MBL). On gestrinone 10 women became amenorrhoeic, in five MBL was markedly reduced (5-74 ml) and four did not respond. In three of the non-responders submucous leiomyomas were found at subsequent hysterectomy. Follow-up periods showed a persistent reduction in MBL for nine women in the first post-treatment menstruation.