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Human Reproduction Update 2009Clinical trials yield discrepant information about the impact of hormone therapy on verbal memory and executive function. This issue is clinically relevant because... (Review)
Review
BACKGROUND
Clinical trials yield discrepant information about the impact of hormone therapy on verbal memory and executive function. This issue is clinically relevant because declines in verbal memory are the earliest predictor of Alzheimer's disease and declines in executive function are central to some theories of normal, age-related changes in cognition.
METHODS
We conducted a systematic review of randomized clinical trials of hormone therapy (i.e. oral, transdermal, i.m.) and verbal memory, distinguishing studies in younger (i.e.
65 years; n = 7) women and studies involving estrogen alone versus estrogen plus progestogen. Out of 32 placebo-controlled trials, 17 were included (13 had no verbal memory measures and 2 involved cholinergic manipulations). We also provide a narrative review of 25 studies of executive function (two trials), since there are insufficient clinical trial data for systematic review. RESULTS
There is some evidence for a beneficial effect of estrogen alone on verbal memory in younger naturally post-menopausal women and more consistent evidence from small-n studies of surgically post-menopausal women. There is stronger evidence of a detrimental effect of conjugated equine estrogen plus medroxyprogesterone acetate on verbal memory in younger and older post-menopausal women. Observational studies and pharmacological models of menopause provide initial evidence of improvements in executive function with hormone therapy.
CONCLUSIONS
Future studies should include measures of executive function and should address pressing clinical questions; including what formulation of combination hormone therapy is cognitively neutral/beneficial, yet effective in treating hot flashes in the early post-menopause.
Topics: Aged; Estrogens; Executive Function; Female; Hormone Replacement Therapy; Humans; Memory; Middle Aged; Randomized Controlled Trials as Topic
PubMed: 19468050
DOI: 10.1093/humupd/dmp022 -
The Cochrane Database of Systematic... Oct 2008Combination injectable contraceptives provide a highly effective, reversible method of preventing pregnancy, and they do not require daily administration or use at the... (Review)
Review
BACKGROUND
Combination injectable contraceptives provide a highly effective, reversible method of preventing pregnancy, and they do not require daily administration or use at the time of coitus. Although they are used in many countries, their acceptability could be limited by method characteristics, such as the need to obtain a monthly injection or bleeding pattern changes.
OBJECTIVES
To assess the contraceptive efficacy, bleeding patterns, discontinuation, user preferences, and side effects of combination injectable contraceptives.
SEARCH STRATEGY
We searched computerized databases for randomized controlled trials of combination injectable contraceptives.
SELECTION CRITERIA
Randomized controlled trials were eligible if they compared a combination injectable with any other contraceptive method (e.g., a second combination injectable contraceptive, progestin-only injectable contraceptive, other hormonal contraceptive or barrier method) or placebo. We limited the review to currently marketed combination injectable contraceptives.
DATA COLLECTION AND ANALYSIS
One author evaluated all titles and abstracts from the literature searches to determine their eligibility. Two authors independently extracted data from the eligible trials. Data on contraceptive efficacy, bleeding patterns, continuation, and side effects were entered and analyzed with RevMan.
MAIN RESULTS
Combination injectable contraceptives include depot medroxyprogesterone acetate (DMPA) 25 mg plus estradiol cypionate (E(2)C) 5 mg, as well as norethisterone enanthate (NET-EN) 50 mg plus estradiol valerate (E(2)V) 5 mg. These contraceptives resulted in lower rates of early study discontinuation due to amenorrhea or other bleeding problems than progestin-only contraceptives. However, rates were higher for overall discontinuation and discontinuation due to other medical reasons. Acceptability results favored the combination injectable in one study and the progestin-only in another.Studies comparing two combination injectable contraceptives found that NET-EN 50 mg plus E(2)V 5 mg resulted in less overall discontinuation and less discontinuation due to amenorrhea or prolonged bleeding than DMPA 25 mg plus E(2)C 5 mg. However, these differences were not detected in all trials. The NET-EN plus E(2)V group also had more regular bleeding and fewer prolonged bleeding reference periods than the DMPA plus E(2)C group. The groups did not differ in their amenorrhea rates.
AUTHORS' CONCLUSIONS
While discontinuation rates can be viewed as a measure of method acceptability, the findings should be interpreted with caution since discontinuation depends on many factors. Future research should be directed toward interventions to improve the acceptability of combination injectable contraceptives, such as providing injections in settings more convenient than clinics, methods for women to administer their own injections, and counseling about possible bleeding pattern changes.
Topics: Algestone; Contraception; Contraceptive Agents, Female; Drug Combinations; Estradiol; Female; Humans; Injections; Medication Adherence; Medroxyprogesterone; Megestrol Acetate; Norethindrone
PubMed: 18843662
DOI: 10.1002/14651858.CD004568.pub3 -
The Cochrane Database of Systematic... Apr 2007Whether steroid contraceptives are appropriate for women with homozygous sickle cell (SS) disease remains unresolved. Historically, women with SS disease have... (Review)
Review
BACKGROUND
Whether steroid contraceptives are appropriate for women with homozygous sickle cell (SS) disease remains unresolved. Historically, women with SS disease have experienced difficult pregnancies, characterized by high rates of maternal mortality and morbidity and poor infant outcomes. Unresolved questions about steroidal contraceptives in women with SS disease include whether using them may promote blood clots.
OBJECTIVES
To assess the safety of steroid hormones in this setting, we retrieved and analyzed all randomized controlled trials that examined steroid hormones for contraception in women with SS disease.
SEARCH STRATEGY
We searched the computerized databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, POPLINE and EMBASE (each from its inception to November, 2005) for randomized controlled trials of steroid hormone use for contraception in women with SS disease. We examined the reference list of each trial as well as that of review articles.
SELECTION CRITERIA
We included any randomized controlled trial in any language that compared steroid hormones for contraception with another contraceptive or placebo. Frequency or intensity of sickle pain crises must have been reported as an outcome.
DATA COLLECTION AND ANALYSIS
We assessed for inclusion all titles and abstracts found. We evaluated the methodological quality of the trial found for potential biases by qualitatively assessing the study design, randomization method, allocation concealment, blinding, premature discontinuation rates, and loss to follow-up rates. We entered trial results in RevMan and reported Peto odds ratios with 95% confidence intervals for dichotomous outcomes, such as occurrence of sickle pain crises.
MAIN RESULTS
Only one trial met the inclusion criteria. Twenty-five patients were randomized to three monthly depo-medroxyprogesterone acetate (DMPA) or intramuscular saline placebo injections in a crossover design. A six-month washout period was implemented before the crossover; however, pharmacological evidence indicates that levels of DMPA may be detected for more than 200 days after the injection. During DMPA use, women were less likely to experience painful sickle episodes (OR 0.23; 95% CI 0.05 to 1.02). No trial involved estrogen products.
AUTHORS' CONCLUSIONS
The limited available data suggest that DMPA is a safe contraceptive option for women in SS disease. In addition to providing effective contraception, DMPA may reduce sickle pain crises.
Topics: Anemia, Sickle Cell; Contraception; Contraceptive Agents, Female; Female; Humans; Medroxyprogesterone Acetate
PubMed: 17443618
DOI: 10.1002/14651858.CD006261.pub2 -
The Cochrane Database of Systematic... Jan 2007Hormonal treatments for advanced or metastatic breast cancer, such as tamoxifen and the progestins megestrol acetate and medroxyprogesterone acetate, have been in use... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hormonal treatments for advanced or metastatic breast cancer, such as tamoxifen and the progestins megestrol acetate and medroxyprogesterone acetate, have been in use for many years. Aromatase inhibitors (AIs) are a class of compounds that systemically inhibit oestrogen synthesis in the peripheral tissues. Aminoglutethimide was the first AI in clinical use (first generation) and had a similar tumour-regressing effect to other endocrine treatments, which showed the potential of this alternative type of therapy. Other AIs have since been developed and the third generation AIs anastrozole, exemestane and letrozole are in current use. Randomised evidence on response rates and side effects of these drugs is still limited.
OBJECTIVES
To compare aromatase inhibitors to other endocrine therapy in the treatment of advanced breast cancer in postmenopausal women.
SEARCH STRATEGY
The Cochrane Breast Cancer Group Specialised Register was searched on 3 December 2004 using the codes for "advanced" and "endocrine therapy". Details of the search strategy applied to create the Register and the procedure used to code references are described in the Cochrane Breast Cancer Group module on The Cochrane Library. The search was updated to 30 September 2005 and additional publications were included. Experts were consulted to determine that no relevant studies had been excluded.
SELECTION CRITERIA
Randomised trials comparing the effects of any aromatase inhibitor versus other endocrine therapy, no endocrine therapy or a different aromatase inhibitor in the treatment of advanced (metastatic) breast cancer.
DATA COLLECTION AND ANALYSIS
Data from published trials were extracted by two independent review authors. A third independent author then carried out a further cross check for accuracy and consistency. Hazard ratios (HR) were derived for analysis of time-to-event outcomes (overall and progression-free). Odds ratios (OR) were derived for objective response and clinical benefit (both analysed as dichotomous variables). Toxicity data were extracted where present and treatments were compared using odds ratios. All but one of the studies included data on one or more of the following outcomes: overall survival, progression-free survival, clinical benefit and objective response.
MAIN RESULTS
Thirty studies were identified, twenty five of which were included in the main analysis of any AI versus any other treatment (9416 women). The pooled estimate showed a significant survival benefit for treatment with an AI over other endocrine therapies (HR 0.89, 95%CI 0.82 to 0.96). A subgroup analysis of the three commonly prescribed AIs (anastrozole, exemestane, letrozole) also showed a similar survival benefit (HR 0.88, 95%CI 0.80 to 0.96). The results for progression-free survival, clinical benefit and objective response were not statistically significant and there was statistically significant heterogeneity across types of AI. There were very limited data to compare one AI with a different AI, but these suggested an advantage for letrozole over anastrozole. All the trials of AIs used exclusively as first-line therapy were against tamoxifen. There was an advantage to treatment with AIs in terms of progression-free survival (HR 0.78, 95% CI 0.70 to 0.86) and clinical benefit (OR 0.70, 95% CI 0.51 to 0.97) but not overall survival or objective response. There was considerable heterogeneity across studies when considering clinical benefit (P = 0.001). Use of an AI as second-line therapy showed a significant benefit in terms of overall survival (HR 0.80, 95% CI 0.66 to 0.96) but not for progression-free survival (HR 1.08, 95% CI 0.89 to 1.31), clinical benefit (OR 1.00, 95% CI 0.87 to 1.14) or objective response (OR 0.96, 95% CI 0.81 to 1.14). This is difficult to interpret due to the extreme heterogeneity across AIs for progression-free survival but not the other endpoints.AIs have a different toxicity profile to other endocrine therapies. For all AIs combined, they had similar levels of hot flushes (especially when compared to tamoxifen) and arthralgia, increased risks of nausea, diarrhoea and vomiting, but a decreased risk of vaginal bleeding and thromboembolic events compared with other endocrine therapies. A similar pattern of risks and benefits was still seen when analyses were limited to the currently most-prescribed third generation AIs.
AUTHORS' CONCLUSIONS
In women with advanced (metastatic) breast cancer, aromatase inhibitors including those in current clinical use show a survival benefit when compared to other endocrine therapy.
Topics: Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Female; Humans; Neoplasms, Hormone-Dependent; Randomized Controlled Trials as Topic
PubMed: 17253488
DOI: 10.1002/14651858.CD003370.pub2 -
Annals of Oncology : Official Journal... Mar 2001The aim of the present study was to summarise evidence from scientific studies on cancer anorexia-cachexia syndrome in order to assess and highlight the efficacy of... (Review)
Review
BACKGROUND
The aim of the present study was to summarise evidence from scientific studies on cancer anorexia-cachexia syndrome in order to assess and highlight the efficacy of high-dose progestins (megestrol acetate and medroxyprogesterone acetate) compared with placebo in patients with hormone-independent tumors.
MATERIALS AND METHODS
A systematic review of published randomised clinical trials was carried out by an extensive electronic and hand search through databases, relevant journals and books, congress, proceedings, reference lists, without any language or year of publication restriction. The research was conducted by two independent operators who collected the data in a form specifically designed for this review. Among the several possible outcomes, appetite and body weight were chosen.
RESULTS
Fifteen randomised clinical trials (more than 2000 patients) were retrieved for the review. There was a statistically significant advantage for high-dose progestins as regards improved appetite: pooled odds ratio (OR) = 4.23, 95% confidence interval (CI): 2.53-7.04. Although the effect of high-dose progestins on body weight was less impressive, statistical significance was also reached for this outcome: pooled OR = 2.66, 95% CI: 1.80-3.92. Treatment morbidity was very low, due to the brief period of the treatment in most of the studies.
CONCLUSIONS
The effects of high-dose progestins on appetite and body weight were clearly demonstrated. However, further studies are undoubtedly warranted to investigate other aspects of progestin activity, especially as regards dosage, duration and timing with best therapeutic index.
Topics: Anorexia; Appetite; Body Weight; Cachexia; Cross-Over Studies; Double-Blind Method; Humans; Neoplasms; Progestins; Prospective Studies; Randomized Controlled Trials as Topic; Syndrome
PubMed: 11332139
DOI: 10.1023/a:1011156811739