Background
Progestin-only contraceptives (POCs) are appropriate for many women who cannot or should not take estrogen. POCs include injectables, intrauterine contraception, implants, and oral contraceptives. Many POCs are long-acting, cost-effective methods of preventing pregnancy. However, concern about weight gain can deter the initiation of contraceptives and cause early discontinuation among users.

Objectives
The primary objective was to evaluate the association between progestin-only contraceptive use and changes in body weight.

Search methods
Until 4 August 2016, we searched MEDLINE, CENTRAL, POPLINE, LILACS, ClinicalTrials.gov, and ICTRP. For the initial review, we contacted investigators to identify other trials.

Selection criteria
We considered comparative studies that examined a POC versus another contraceptive method or no contraceptive. The primary outcome was mean change in body weight or mean change in body composition. We also considered the dichotomous outcome of loss or gain of a specified amount of weight.

Data collection and analysis
Two authors extracted the data. Non-randomized studies (NRS) need to control for confounding factors. We used adjusted measures for the primary effects in NRS or the results of matched analysis from paired samples. If the report did not provide adjusted measures for the primary analysis, we used unadjusted outcomes. For RCTs and NRS without adjusted measures, we computed the mean difference (MD) with 95% confidence interval (CI) for continuous variables. For dichotomous outcomes, we calculated the Mantel-Haenszel odds ratio (OR) with 95% CI.

Main results
We found 22 eligible studies that included a total of 11,450 women. With 6 NRS added to this update, the review includes 17 NRS and 5 RCTs. By contraceptive method, the review has 16 studies of depot medroxyprogesterone acetate (DMPA), 4 of levonorgestrel-releasing intrauterine contraception (LNG-IUC), 5 for implants, and 2 for progestin-only pills.

Comparison groups did not differ significantly for weight change or other body composition measure in 15 studies. Five studies with moderate or low quality evidence showed differences between study arms. Two studies of a six-rod implant also indicated some differences, but the evidence was low quality.

Three studies showed differences for DMPA users compared with women not using a hormonal method. In a retrospective study, weight gain (kg) was greater for DMPA versus copper (Cu) IUC in years one (MD 2.28, 95% CI 1.79 to 2.77), two (MD 2.71, 95% CI 2.12 to 3.30), and three (MD 3.17, 95% CI 2.51 to 3.83). A prospective study showed adolescents using DMPA had a greater increase in body fat (%) compared with a group not using a hormonal method (MD 11.00, 95% CI 2.64 to 19.36). The DMPA group also had a greater decrease in lean body mass (%) (MD -4.00, 95% CI -6.93 to -1.07). A more recent retrospective study reported greater mean increases with use of DMPA versus Cu IUC for weight (kg) at years 1 (1.3 vs 0.2), 4 (3.5 vs 1.9), and 10 (6.6 vs 4.9).

Two studies reported a greater mean increase in body fat mass (%) for POC users versus women not using a hormonal method. The method was LNG-IUC in two studies (reported means 2.5 versus -1.3; P = 0.029); (MD 1.60, 95% CI 0.45 to 2.75). One also studied a desogestrel-containing pill (MD 3.30, 95% CI 2.08 to 4.52). Both studies showed a greater decrease in lean body mass among POC users.

Authors' conclusions
We considered the overall quality of evidence to be low; more than half of the studies had low quality evidence. The main reasons for downgrading were lack of randomizations (NRS) and high loss to follow-up or early discontinuation.

These 22 studies showed limited evidence of change in weight or body composition with use of POCs. Mean weight gain at 6 or 12 months was less than 2 kg (4.4 lb) for most studies. Those with multiyear data showed mean weight change was approximately twice as much at two to four years than at one year, but generally the study groups did not differ significantly. Appropriate counseling about typical weight gain may help reduce discontinuation of contraceptives due to perceptions of weight gain.

Progestin‐only contraceptives: effects on weight

Importance Nearly half of postmenopausal women report bothersome vulvovaginal symptoms, but few data support the efficacy of 2 commonly recommended treatments. Objective To compare the efficacy of a low-dose vaginal estradiol tablet and a vaginal moisturizer, each vs placebo, for treatment of moderate-to-severe postmenopausal vulvovaginal symptoms. Design, Setting, and Participants This 12-week multicenter randomized clinical trial enrolled postmenopausal women with moderate to severe symptoms of vulvovaginal itching, pain, dryness, irritation, or pain with penetration. Interventions Vaginal 10-μg estradiol tablet (daily for 2 weeks, then twice weekly) plus placebo gel (3 times a week) (n = 102) vs placebo tablet plus vaginal moisturizer (n = 100) vs dual placebo (n = 100). Main Outcomes and Measures The main outcome was decrease in severity (0-3) of most bothersome symptom (MBS) between enrollment and 12 weeks. Additional measures included a composite vaginal symptom score, Female Sexual Function Index (FSFI) score (2-36), modified Female Sexual Distress Score–Revised item 1, treatment satisfaction and meaningful benefit, Vaginal Maturation Index, and vaginal pH. Results The 302 women had a mean (SD) age of 61 (4) years and were primarily white (267 [88%]), college educated (200 [66%]), and sexually active (245 [81%]). Most women (294 [97%]) provided data for the primary analysis. The most commonly reported MBS was pain with vaginal penetration (182 [60%]), followed by vulvovaginal dryness (63 [21%]). Mean baseline MBS severity was similar between treatment groups: estradiol, 2.4 (95% CI, 2.3 to 2.6); moisturizer, 2.5 (95% CI, 2.3 to 2.6); placebo, 2.5 (95% CI, 2.4 to 2.6). All treatment groups had similar mean reductions in MBS severity over 12 weeks: estradiol, −1.4 (95% CI, −1.6 to −1.2); moisturizer, −1.2 (95% CI, −1.4 to −1.0); and placebo, −1.3 (95% CI, −1.5 to −1.1). No significant differences were seen between estradiol ( P  = .25) or moisturizer ( P  = .31) compared with placebo. Mean total FSFI improvement was similar between estradiol (5.4; 95% CI, 4.0 to 6.9) and placebo (4.5; 95% CI, 2.8 to 6.1) ( P  = .64), and between moisturizer (3.1; 95% CI, 1.7 to 4.5) and placebo ( P  = .17). Conclusions and Relevance Our results suggest that neither prescribed vaginal estradiol tablet nor over-the-counter vaginal moisturizer provides additional benefit over placebo vaginal tablet and gel in reducing postmenopausal vulvovaginal symptoms. Trial Registration clinicaltrials.gov Identifier:NCT02516202

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Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms: A Randomized Clinical Trial.

There is a new appreciation of the perimenopause - defined as the early and late menopause transition stages as well as the early postmenopause - as a window of vulnerability for the development of both depressive symptoms and major depressive episodes. However, clinical recommendations on how to identify, characterize and treat clinical depression are lacking. To address this gap, an expert panel was convened to systematically review the published literature and develop guidelines on the evaluation and management of perimenopausal depression. The areas addressed included: 1) epidemiology; 2) clinical presentation; 3) therapeutic effects of antidepressants; 4) effects of hormone therapy; and 5) efficacy of other therapies (eg, psychotherapy, exercise, and natural health products). Overall, evidence generally suggests that most midlife women who experience a major depressive episode during the perimenopause have experienced a prior episode of depression. Midlife depression presents with classic depressive symptoms commonly in combination with menopause symptoms (ie, vasomotor symptoms, sleep disturbance), and psychosocial challenges. Menopause symptoms complicate, co-occur, and overlap with the presentation of depression. Diagnosis involves identification of menopausal stage, assessment of co-occurring psychiatric and menopause symptoms, appreciation of the psychosocial factors common in midlife, differential diagnoses, and the use of validated screening instruments. Proven therapeutic options for depression (ie, antidepressants, psychotherapy) are the front-line treatments for perimenopausal depression. Although estrogen therapy is not approved to treat perimenopausal depression, there is evidence that it has antidepressant effects in perimenopausal women, particularly those with concomitant vasomotor symptoms. Data on estrogen plus progestin are sparse and inconclusive.

Guidelines for the evaluation and treatment of perimenopausal depression: summary and recommendations.

Folic acid is a member of the B-vitamin family and is essential for amino acid metabolism. Adequate intake of folic acid is vital for metabolism, cellular homeostasis, and DNA synthesis. Since the initial discovery of folic acid in the 1940s, folate deficiency has been implicated in numerous disease states, primarily those associated with neural tube defects in utero and neurological degeneration later in life. However, in the past decade, epidemiological studies have identified an inverse relation between both folic acid intake and blood folate concentration and cardiovascular health. This association inspired a number of clinical studies that suggested that folic acid supplementation could reverse endothelial dysfunction in patients with cardiovascular disease (CVD). Recently, in vitro and in vivo studies have begun to elucidate the mechanism(s) through which folic acid improves vascular endothelial function. These studies, which are the focus of this review, suggest that folic acid and its active metabolite 5-methyl tetrahydrofolate improve nitric oxide (NO) bioavailability by increasing endothelial NO synthase coupling and NO production as well as by directly scavenging superoxide radicals. By improving NO bioavailability, folic acid may protect or improve endothelial function, thereby preventing or reversing the progression of CVD in those with overt disease or elevated CVD risk.

Role of folic acid in nitric oxide bioavailability and vascular endothelial function.

Depression during the perimenopause : A meta-analysis

Vaginal atrophy of women in postmenopause. Results from a multicentric observational study: The AGATA study.

Objectives: This study aimed to determine the frequency of dysmenorrhea, as identified by different definitions, in a population of young women, and to investigate factors associated with this complaint. Materials and methods: A final group of 408 young women completed a self-assessment questionnaire. This was a cross-sectional analytical study. Results: Menstrual pain was reported by 84.1% of women, with 43.1% reporting that pain occurred during every period, and 41% reporting that pain occurred during some periods. Women with menstrual pain had an earlier menarche (P = 0.0002) and a longer menstrual flow ( P = 0.006), and this group was characterized as having a higher prevalence of smokers (P = 0.031) and a lower prevalence of hormonal contraception users (P = 0.015). Pain intensity was correlated (r = 0.302, P , 0.0001) positively with menstrual flow length (CR = 0.336), history of abortions (CR = 3.640), and gynecological pathologies (CR = 0.948), and negatively with age at menarche (CR = -0.225), use of hormonal contraception (CR = -0.787), and history of gynecological surgery (CR = -2.115). Considering the parameters of menstrual pain, a need for medication, and inability to function normally (absenteeism from study or social activities) alone or together, the prevalence of dysmenorrhea is 84.1% when considering only menstrual pain, 55.2% when considering the association between menstrual pain and need for medication, 31.9% when considering the association between menstrual pain and absenteeism, and 25.3% when considering the association between menstrual pain, need for medication, and absenteeism (P , 0.0001). The probability of having more severe dysmenorrhea is directly related to pain intensity as measured by a visual analog scale, but does not coincide with it. Conclusion: Menstrual pain is a very common problem, but the need for medication and the inability to function normally occurs less frequently. Nevertheless, at least one in four women experiences distressing menstrual pain characterized by a need for medication and absenteeism from study or social activities.

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Prevalence of menstrual pain in young women: what is dysmenorrhea?

Objectives Conflicting evidence indicates an increased risk for cardiovascular disease in postmenopausal women suffering from hot flushes. In this study, we tested whether, beyond hot flushes, menopausal symptoms are associated with biochemical and biophysical risk factors for cardiovascular disease.Methods Retrospective cross-sectional analysis on 951 women in surgical or physiological postmenopause, recruited at the menopause outpatient service of our university hospital between April 2002 and December 2009. The Greene Climacteric Scale and its subscales for anxiety, depression, somatic symptoms, vasomotor symptoms and sexuality were used to evaluate menopausal complaints. Blood pressure, fasting glucose and lipids levels were evaluated as risk factors for cardiovascular disease. Anthropometric parameters and those derived by remote and reproductive medical history were used as possible confounders. All data were anonymously retrieved from an electronic database.Results By multiple regression an...

Menopausal symptoms and risk factors for cardiovascular disease in postmenopause

Objective:The progestin dienogest (DNG) given alone effectively reduces pelvic pain of women with endometriosis. It is not clear whether the same occurs when DNG is associated with estradiol (E2).Design:Patient preference prospective observational study.Setting:Outpatient centre of university hospital.Patients:40 patients with endometriosis and menstrual pain.Interventions:24-week treatment with a quadriphasic association of E2 valerate (E2V) and DNG or a nonsteroidal anti-inflammatory drug (NSAID) to be used only in case of pain (ketoprofene 200-mg tablets).Main Outcome Measures:Menstrual pain and, when present, intermenstrual pain, and dyspareunia were investigated by means of a 10-cm visual analogue scale (VAS). Quality of life was investigated by the short form 36 (SF-36) of the health-related quality of life questionnaire.Results:Final study group consists of 34 patients, 19 in the E2V/DNG group and 15 in the NSAID group. After 24 weeks, no significant modification of menstrual pain, intermenstrual p...

Pelvic pain and quality of life of women with endometriosis during quadriphasic estradiol valerate/dienogest oral contraceptive: a patient-preference prospective 24-week pilot study.

Objectives: This study aimed to investigate the prevalence of vaginal atrophy (VA) in women across the menopausal age.Methods: A multicenter cross-sectional investigation was performed on 747 femal...

Federica Palma

Papers

Vaginal atrophy of women in postmenopause. Results from a multicentric observational study: The AGATA study.

Prevalence of menstrual pain in young women: what is dysmenorrhea?

Menopausal symptoms and risk factors for cardiovascular disease in postmenopause

Pelvic pain and quality of life of women with endometriosis during quadriphasic estradiol valerate/dienogest oral contraceptive: a patient-preference prospective 24-week pilot study.

Vaginal atrophy across the menopausal age: results from the ANGEL study