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Clinical Endocrinology May 2021Antiandrogens are frequently used with estradiol in transgender women seeking feminization. Antiandrogens act by various mechanisms to decrease the production or effects... (Review)
Review
Antiandrogens are frequently used with estradiol in transgender women seeking feminization. Antiandrogens act by various mechanisms to decrease the production or effects of testosterone, but it is unclear which antiandrogen is most effective at feminization. A systematic review was performed using PRISMA guidelines. We searched online databases (Medline, Embase and PsycINFO) and references of relevant articles for studies of antiandrogens in transgender women aged 16+ years to achieve feminization (namely changes in breast size, body composition, facial or body hair) or changes in serum total testosterone concentration when compared to placebo, estradiol alone or an alternative antiandrogen. Four studies fulfilled eligibility criteria and were included in a narrative review. The addition of cyproterone acetate, leuprolide and medroxyprogesterone acetate may be more effective than spironolactone or estradiol alone at suppressing the serum total testosterone concentration. Body composition changes appear similar in transgender women treated with estradiol and additional cyproterone acetate or leuprolide. No eligible studies adequately evaluated the effects of antiandrogens on breast development or facial and body hair reduction. It remains unclear which antiandrogen is most effective at achieving feminization. Cyproterone acetate, medroxyprogesterone acetate and leuprolide may be more effective than spironolactone at suppressing the serum total testosterone concentration. However, due to spironolactone's antagonism of the androgen receptor, it is unclear whether this results in clinically meaningful differences in feminization. Further research with clinically meaningful endpoints is needed to optimize the use of antiandrogens in transgender women.
Topics: Androgen Antagonists; Cyproterone Acetate; Female; Feminization; Humans; Male; Transgender Persons; Transsexualism
PubMed: 32926454
DOI: 10.1111/cen.14329 -
Climacteric : the Journal of the... Dec 2020Uterine bleeding is a common reason why women discontinue menopausal hormone therapy (HT). This systematic review compared bleeding profiles reported in studies for...
Uterine bleeding is a common reason why women discontinue menopausal hormone therapy (HT). This systematic review compared bleeding profiles reported in studies for continuous-combined HT approved in North America and Europe for moderate to severe vasomotor symptoms in postmenopausal women with a uterus. Non-head-to-head studies showed that uterine bleeding varies by formulation and administration route, with oral having a better bleeding profile than transdermal formulations. Cumulative amenorrhea over a year ranged from 18 to 61% with oral HT and from 9 to 27% with transdermal HT, as reported for continuous-combined HT containing 17β-estradiol (E2)/progesterone (P4) (56%), E2/norethisterone acetate (NETA) (49%), E2/drospirenone (45%), conjugated equine estrogens/medroxyprogesterone acetate (18-54%), ethinyl estradiol/NETA (31-61%), E2/levonorgestrel patch (16%), and E2/NETA patch (9-27%). Amenorrhea rates and the mean number of bleeding/spotting days improved over time. The oral E2/P4 combination was amongst those with lower bleeding rates and may be an appropriate alternative for millions of women seeking bioidentical HT and/or those who have bleeding concerns with other HT.
Topics: Administration, Cutaneous; Administration, Oral; Estrogen Replacement Therapy; Estrogens; Female; Humans; Menopause; Middle Aged; Progesterone; Uterine Hemorrhage
PubMed: 32893694
DOI: 10.1080/13697137.2020.1806816 -
The Lancet. Diabetes & Endocrinology Aug 2020The validation of bone mineral density (BMD) as a surrogate outcome for fracture would allow the size of future randomised controlled osteoporosis registration trials to... (Meta-Analysis)
Meta-Analysis
Treatment-related changes in bone mineral density as a surrogate biomarker for fracture risk reduction: meta-regression analyses of individual patient data from multiple randomised controlled trials.
BACKGROUND
The validation of bone mineral density (BMD) as a surrogate outcome for fracture would allow the size of future randomised controlled osteoporosis registration trials to be reduced. We aimed to determine the association between treatment-related changes in BMD, assessed by dual-energy x-ray absorptiometry, and fracture outcomes, including the proportion of treatment effect explained by BMD changes.
METHODS
We did a pooled analysis of individual patient data from multiple randomised placebo-controlled clinical trials. We included data from multicentre, randomised, placebo-controlled, double-blind trials of osteoporosis medications that included women and men at increased osteoporotic fracture risk. Using individual patient data for each trial we calculated mean 24-month BMD percent change together with fracture reductions and did a meta-regression of the association between treatment-related differences in BMD changes (percentage difference, active minus placebo) and fracture risk reduction. We also used individual patient data to determine the proportion of anti-fracture treatment effect explained by BMD changes and the BMD change needed in future trials to ensure fracture reduction efficacy.
FINDINGS
Individual patient data from 91 779 participants of 23 randomised, placebo-controlled trials were included. The trials had 1-9 years of follow-up and included 12 trials of bisphosphonate, one of odanacatib, two of hormone therapy (one of conjugated equine oestrogen and one of conjugated equine oestrogen plus medroxyprogesterone acetate), three of PTH receptor agonists, one of denosumab, and four of selective oestrogen receptor modulator trials. The meta-regression revealed significant associations between treatment-related changes in hip, femoral neck, and spine BMD and reductions in vertebral (r 0·73, p<0·0001; 0·59, p=0·0005; 0·61, p=0·0003), hip (0·41, p=0·014; 0·41, p=0·0074; 0·34, p=0·023) and non-vertebral fractures (0·53, p=0·0021; 0·65, p<0·0001; 0·51, p=0·0019). Minimum 24-month percentage changes in total hip BMD providing almost certain fracture reductions in future trials ranged from 1·42% to 3·18%, depending on fracture site. Hip BMD changes explained substantial proportions (44-67%) of treatment-related fracture risk reduction.
INTERPRETATION
Treatment-related BMD changes are strongly associated with fracture reductions across randomised trials of osteoporosis therapies with differing mechanisms of action. These analyses support BMD as a surrogate outcome for fracture outcomes in future randomised trials of new osteoporosis therapies and provide an important demonstration of the value of public access to individual patient data from multiple trials.
FUNDING
Foundation for National Institutes of Health.
Topics: Absorptiometry, Photon; Biomarkers; Bone Density; Bone Density Conservation Agents; Data Interpretation, Statistical; Humans; Osteoporotic Fractures; Randomized Controlled Trials as Topic; Regression Analysis; Risk Reduction Behavior; Treatment Outcome
PubMed: 32707115
DOI: 10.1016/S2213-8587(20)30159-5 -
The Cochrane Database of Systematic... Jul 2020Within the context of heavy menstrual bleeding, pandemics impact upon women's assessment and treatment by healthcare providers.
BACKGROUND
Within the context of heavy menstrual bleeding, pandemics impact upon women's assessment and treatment by healthcare providers.
OBJECTIVES
To summarise the evidence from Cochrane Reviews evaluating interventions for heavy menstrual bleeding that are commonly available during pandemics.
METHODS
We sought published Cochrane Reviews, evaluating interventions that can continue during pandemics for women with heavy menstrual bleeding with no known underlying cause. We identified Cochrane Reviews by searching the Cochrane Database of Systematic Reviews in June 2020. The primary outcome was menstrual bleeding. Secondary outcomes included quality of life, patient satisfaction, side effects, and serious adverse events. We undertook the selection of systematic reviews, data extraction, and quality assessment in duplicate. We resolved any disagreements by discussion. We assessed review quality using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) 2 tool, and the certainty of the evidence for each outcome using GRADE methods.
MAIN RESULTS
We included four Cochrane Reviews, with 11 comparisons, data from 44 randomised controlled trials (RCTs), and 3196 women. We assessed all the reviews to be high quality. Non-steroidal anti-inflammatory drugs (NSAIDs) NSAIDs may be more effective in reducing heavy menstrual bleeding than placebo (mean difference (MD) -124 mL per cycle, 95% confidence interval (CI) -186 to -62 mL per cycle; 1 RCT, 11 women; low-certainty evidence). Mefenamic acid may be similar to naproxen (MD 21 mL per cycle, 95% CI -6 to 48 mL per cycle; 2 RCTs, 61 women; low-certainty evidence), and NSAIDs may be similar to combined hormonal contraceptives for heavy menstrual bleeding (MD 25 mL per cycle, 95% CI -22 to 73 mL per cycle; 1 RCT, 26 women; low-certainty evidence). NSAIDs may be be less effective in reducing menstrual bleeding than antifibrinolytics (relative risk (RR) 0.70, 95% CI 0.58 to 0.85; 2 RCTs, 161 women; low-certainty evidence). We are uncertain whether NSAIDs reduce menstrual blood loss more than short-cycle progestogens (RR 0.80, 95% CI 0.49 to 1.32; 1 RCT 32 women; very low-certainty evidence). Antifibrinolytics Antifibrinolytics appear to be more effective in reducing heavy menstrual bleeding than placebo (MD -53 mL per cycle, 95% CI -63 to -44 mL per cycle; 4 RCTs, 565 women; moderate-certainty evidence). Antifibrinolytics may be similar to placebo on the incidence of side effects (RR 1.05, 95% CI 0.93 to 1.18; 1 RCT, 297 women; low-certainty evidence), and they are probably similar on the incidence of serious adverse events (thrombotic events; RR 0.10, 95% CI 0.00 to 2.46; 2 RCT, 468 women; moderate-certainty evidence). Antifibrinolytics may be more effective in reducing heavy menstrual bleeding than short-cycle progestogen (MD -111 mL per cycle, 95% CI -178 mL to -44 mL per cycle; 1 RCT, 46 women; low-certainty evidence). We are uncertain whether antifibrinolytics are similar to short-cycle progestogens on quality of life (RR 1.67, 95% CI 0.76 to 3.64; 1 RCT, 44 women; very low-certainty evidence), patient satisfaction (RR 0.91, 95% CI 0.59 to 1.39; 1 RCT, 42 women; very low-certainty evidence), or side effects (RR 0.85, 95% CI 0.65 to 1.12; 3 RCTs, 211 women; very low-certainty evidence). We are uncertain whether antifibrinolytics are more effective in reducing heavy menstrual bleeding when compared with long-cycle progestogen (MD -9 points per cycle, 95% CI -30 to 12 points per cycle; 2 RCTs, 184 women; low-certainty evidence). Antifibrinolytics may increase self-reported improvement in menstrual bleeding when compared with long-cycle medroxyprogesterone acetate (RR 1.32, 95% CI 1.08 to 1.61; 1 RCT, 94 women; low-certainty evidence). Antifibrinolytics may be similar to long-cycle progestogens on quality of life (MD 5, 95% CI -2.49 to 12.49; 1 RCT, 90 women; low-certainty evidence). We are uncertain whether antifibrinolytics are similar to long-cycle progestogens on side effects (RR 0.58, 95% CI 0.33 to 1.00; 2 RCTs, 184 women; very low-certainty evidence). There were no trials comparing antifibrinolytics to combined hormonal contraceptives. Combined hormonal contraceptives Combined hormonal contraceptives appear to be more effective for heavy menstrual bleeding than placebo or no treatment (RR 13.25, 95% CI 2.94 to 59.64; 2 RCTs, 363 women; moderate-certainty evidence). Combined hormonal contraceptives are probably similar to placebo on the incidence of side effects (RR 1.53, 95% CI 0.90 to 2.60; 2 RCTs, 411 women; moderate-certainty evidence). Progestogens There were no trials comparing progestogens to placebo. Limitations in the evidence included risk of bias in the primary RCTs, inconsistency between the primary RCTs, and imprecision in effect estimates.
AUTHORS' CONCLUSIONS
There is moderate-certainty evidence that antifibrinolytics and combined hormonal contraceptives reduce heavy menstrual bleeding compared with placebo. There is low-certainty evidence that NSAIDs reduce heavy menstrual bleeding compared with placebo. There is low-certainty evidence that antifibrinolytics are more effective in reducing heavy menstrual bleeding when compared with NSAIDs and short-cycle progestogens, but we are unable to draw conclusions about the effects of antifibrinolytics compared to long-cycle progestogens, on low-certainty evidence.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antifibrinolytic Agents; Contraceptives, Oral, Hormonal; Female; Humans; Mefenamic Acid; Menorrhagia; Pandemics; Placebos; Progestins; Randomized Controlled Trials as Topic; Review Literature as Topic
PubMed: 32700364
DOI: 10.1002/14651858.CD013651.pub2 -
Medicine Jun 2020Atypical polypoid adenomyoma (APA) is a rare uterine tumor typically found in fertile age and associated with infertility. Among young nullipara women, conservative... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atypical polypoid adenomyoma (APA) is a rare uterine tumor typically found in fertile age and associated with infertility. Among young nullipara women, conservative treatment is proposed despite the high recurrence rate and the association with endometrial cancer.Our aim was to assess the risk of recurrence with different conservative treatments in fertile ages and the prevalence of malignant or pre-malignant associated lesions to better address an adequate patient counselling when treatment modalities are discussed.
METHODS
This study is a systematic review and meta-analysis of case reports and case series about APA management and follow-up. A literature search was carried from Medline and Scopus for studies published from January 1, 1980 to December 31, 2018.
RESULTS
We included 46 observational studies and 296 cases in fertile women. The prevalence of APA relapse was 44% (CI.95 33-57%) and was lower in cases treated with operative hysteroscopy (22%; CI.95 11-39%) than in cases treated with blind curettage and polypectomy (38%; CI.95 15-67%). The prevalence of the concomitant or during the follow-up diagnosis of endometrial carcinoma was 16% (CI.95 9-29%). The risk of cancer development during follow-up was significantly less in cases treated with histeroscopy (10.56% new cumulative diagnosis at 5 years follow up; CI.95 0-23.7%) than blind curettage and polypectomy (35.5% new cumulative diagnosis at 5 years; CI.95 11.65-52.92%; P < .05). Medical treatment with medroxyprogesterone acetate after surgery does not reduce APA recurrence. Pregnancy was observed in 79% cases in which the desire was expressed.
CONCLUSION
This review suggests that conservative treatment performed by operative hysteroscopy is the optimal choice because it lowers the risk of recurrence, improves the accuracy of concomitant carcinoma or hyperplasia diagnosis, and leaves the possibility of future pregnancies.
Topics: Adenomyoma; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Conservative Treatment; Curettage; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Humans; Hysteroscopy; Medroxyprogesterone Acetate; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Pregnancy; Pregnancy Rate; Uterine Neoplasms
PubMed: 32590732
DOI: 10.1097/MD.0000000000020491 -
The Cochrane Database of Systematic... Jun 2020Heavy menstrual bleeding (HMB) impacts the quality of life of otherwise healthy women. The perception of HMB is subjective and management depends upon, among other... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Heavy menstrual bleeding (HMB) impacts the quality of life of otherwise healthy women. The perception of HMB is subjective and management depends upon, among other factors, the severity of the symptoms, a woman's age, her wish to get pregnant, and the presence of other pathologies. Heavy menstrual bleeding was classically defined as greater than or equal to 80 mL of blood loss per menstrual cycle. Currently the definition is based on the woman's perception of excessive bleeding which is affecting her quality of life. The intrauterine device was originally developed as a contraceptive but the addition of progestogens to these devices resulted in a large reduction in menstrual blood loss: users of the levonorgestrel-releasing intrauterine system (LNG-IUS) reported reductions of up to 90%. Insertion may, however, be regarded as invasive by some women, which affects its acceptability.
OBJECTIVES
To determine the effectiveness, acceptability and safety of progestogen-releasing intrauterine devices in reducing heavy menstrual bleeding.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL (from inception to June 2019); and we searched grey literature and for unpublished trials in trial registers.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in women of reproductive age treated with LNG-IUS devices versus no treatment, placebo, or other medical or surgical therapy for heavy menstrual bleeding.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data, assessed risk of bias and conducted GRADE assessments of the certainty of evidence.
MAIN RESULTS
We included 25 RCTs (2511 women). Limitations in the evidence included risk of attrition bias and low numbers of participants. The studies compared the following interventions. LNG-IUS versus other medical therapy The other medical therapies were norethisterone acetate, medroxyprogesterone acetate, oral contraceptive pill, mefenamic acid, tranexamic acid or usual medical treatment (where participants could choose the oral treatment that was most suitable). The LNG-IUS may improve HMB, lowering menstrual blood loss according to the alkaline haematin method (mean difference (MD) 66.91 mL, 95% confidence interval (CI) 42.61 to 91.20; 2 studies, 170 women; low-certainty evidence); and the Pictorial Bleeding Assessment Chart (MD 55.05, 95% CI 27.83 to 82.28; 3 studies, 335 women; low-certainty evidence). We are uncertain whether the LNG-IUS may have any effect on women's satisfaction up to one year (RR 1.28, 95% CI 1.01 to 1.63; 3 studies, 141 women; I² = 0%, very low-certainty evidence). The LNG-IUS probably leads to slightly higher quality of life measured with the SF-36 compared with other medical therapy if (MD 2.90, 95% CI 0.06 to 5.74; 1 study: 571 women; moderate-certainty evidence) or with the Menorrhagia Multi-Attribute Scale (MD 13.40, 95% CI 9.89 to 16.91; 1 trial, 571 women; moderate-certainty evidence). The LNG-IUS and other medical therapies probably give rise to similar numbers of women with serious adverse events (RR 0.91, 95% CI 0.63 to 1.30; 1 study, 571 women; moderate-certainty evidence). Women using other medical therapy are probably more likely to withdraw from treatment for any reason (RR 0.49, 95% CI 0.39 to 0.60; 1 study, 571 women, moderate-certainty evidence) and to experience treatment failure than women with LNG-IUS (RR 0.34, 95% CI 0.26 to 0.44; 6 studies, 535 women; moderate-certainty evidence). LNG-IUS versus endometrial resection or ablation (EA) Bleeding outcome results are inconsistent. We are uncertain of the effect of the LNG-IUS compared to EA on rates of amenorrhoea (RR 1.21, 95% CI 0.85 to 1.72; 8 studies, 431 women; I² = 21%; low-certainty evidence) and hypomenorrhoea (RR 0.98, 95% CI 0.73 to 1.33; 4 studies, 200 women; low-certainty evidence) and eumenorrhoea (RR 0.55, 95% CI 0.30 to 1.00; 3 studies, 160 women; very low-certainty evidence). We are uncertain whether both treatments may have similar rates of satisfaction with treatment at 12 months (RR 0.95, 95% CI 0.85 to 1.07; 5 studies, 317 women; low-certainty evidence). We are uncertain if the LNG-IUS compared to EA has any effect on quality of life, measured with SF-36 (MD -14.40, 95% CI -22.63 to -6.17; 1 study, 33 women; very low-certainty evidence). Women with the LNG-IUS compared with EA are probably more likely to have any adverse event (RR 2.06, 95% CI 1.44 to 2.94; 3 studies, 201 women; moderate-certainty evidence). Women with the LNG-IUS may experience more treatment failure compared to EA at one year follow up (persistent HMB or requirement of additional treatment) (RR 1.78, 95% CI 1.09 to 2.90; 5 studies, 320 women; low-certainty evidence); or requirement of hysterectomy may be higher at one year follow up (RR 2.56, 95% CI 1.48 to 4.42; 3 studies, 400 women; low-certainty evidence). LNG-IUS versus hysterectomy We are uncertain whether the LNG-IUS has any effect on HMB compared with hysterectomy (RR for amenorrhoea 0.52, 95% CI 0.39 to 0.70; 1 study, 75 women; very low-certainty evidence). We are uncertain whether there is difference between LNG-IUS and hysterectomy in satisfaction at five years (RR 1.01, 95% CI 0.94 to 1.08; 1 study, 232 women; low-certainty evidence) and quality of life (SF-36 MD 2.20, 95% CI -2.93 to 7.33; 1 study, 221 women; low-certainty evidence). Women in the LNG-IUS group may be more likely to have treatment failure requiring hysterectomy for HMB at 1-year follow-up compared to the hysterectomy group (RR 48.18, 95% CI 2.96 to 783.22; 1 study, 236 women; low-certainty evidence). None of the studies reported cost data suitable for meta-analysis.
AUTHORS' CONCLUSIONS
The LNG-IUS may improve HMB and quality of life compared to other medical therapy; the LNG-IUS is probably similar for HMB compared to endometrial destruction techniques; and we are uncertain if it is better or worse than hysterectomy. The LNG-IUS probably has similar serious adverse events to other medical therapy and it is more likely to have any adverse events than EA.
Topics: Antifibrinolytic Agents; Contraceptives, Oral; Endometrium; Female; Humans; Hysterectomy; Intrauterine Devices, Medicated; Levonorgestrel; Mefenamic Acid; Menorrhagia; Norethindrone; Progesterone; Quality of Life; Randomized Controlled Trials as Topic; Tranexamic Acid; Treatment Outcome
PubMed: 32529637
DOI: 10.1002/14651858.CD002126.pub4 -
BMJ Sexual & Reproductive Health Jan 2020To review systematically copper intrauterine device (Cu-IUD) use and HIV acquisition in women.
OBJECTIVES
To review systematically copper intrauterine device (Cu-IUD) use and HIV acquisition in women.
METHODS
We searched Pubmed, Embase and the Cochrane Library between database inception and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using an unspecified IUD or Cu-IUD compared with non-hormonal or no contraceptive users, or hormonal contraceptive users. We extracted information from included studies, assessed study quality, and summarised study findings.
RESULTS
From 2494 publications identified, seven met our inclusion criteria. One randomised controlled trial (RCT), judged "informative with few limitations", found no statistically significant differences in HIV risk between users of the Cu-IUD and either intramuscular depot medroxyprogesterone acetate (DMPA-IM) or levonorgestrel implant. One observational study, deemed "informative but with important limitations", found no statistically significant difference in HIV incidence among IUD users compared with women who had tubal ligation or who were not using any contraception. Another "informative but with important limitations" observational study found no difference in HIV incidence between Cu-IUD users and DMPA or norethisterone enanthate injectable, or implant users. An RCT considered "unlikely to inform the primary question" also found no difference in HIV risk between Cu-IUD and progestogen-only injectable users. Findings from the other three "unlikely to inform the primary question" cohort studies were consistent with the more robust studies suggesting no increased risk of HIV acquisition among Cu-IUD users.
CONCLUSION
The collective evidence, including that from a large high-quality RCT, does not indicate an increased risk of HIV acquisition among users of Cu-IUDs.
Topics: Adolescent; Adult; Contraception Behavior; Female; HIV Infections; Humans; Incidence; Intrauterine Devices, Copper
PubMed: 31919240
DOI: 10.1136/bmjsrh-2019-200512 -
BMJ Sexual & Reproductive Health Jan 2020To update a 2016 systematic review on hormonal contraception use and HIV acquisition.
OBJECTIVE
To update a 2016 systematic review on hormonal contraception use and HIV acquisition.
METHODS
We searched Pubmed and Embase between 15 January 2016 and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using a hormonal contraceptive method and either non-users or users of another specific hormonal contraceptive method. We extracted information from newly identified studies, assessed study quality, and updated forest plots and meta-analyses.
RESULTS
In addition to 31 previously included studies, five more were identified; three provided higher quality evidence. A randomised clinical trial (RCT) found no statistically significant differences in HIV risk among users of intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG implant) or the copper intrauterine device (Cu-IUD). An observational study found no statistically significant differences in HIV risk among women using DMPA, norethisterone enanthate (NET-EN), implants (type not specified) or Cu-IUD. Updated results from a previously included observational study continued to find a statistically significant increased HIV risk with oral contraceptives and DMPA compared with no contraceptive use, and found no association between LNG implant and HIV risk.
CONCLUSIONS
High-quality RCT data comparing use of DMPA, LNG implant and Cu-IUD does not support previous concerns from observational studies that DMPA-IM use increases the risk of HIV acquisition. Use of other hormonal contraceptive methods (oral contraceptives, NET-EN and implants) is not associated with an increased risk of HIV acquisition.
Topics: Adolescent; Adult; Female; HIV Infections; Hormonal Contraception; Humans
PubMed: 31919239
DOI: 10.1136/bmjsrh-2019-200509 -
Handbook of Experimental Pharmacology 2020Drugs may cause bone loss by lowering sex steroid levels (e.g., aromatase inhibitors in breast cancer, GnRH agonists in prostate cancer, or depot medroxyprogestone...
Drugs may cause bone loss by lowering sex steroid levels (e.g., aromatase inhibitors in breast cancer, GnRH agonists in prostate cancer, or depot medroxyprogestone acetate - DMPA), interfere with vitamin D levels (liver inducing anti-epileptic drugs), or directly by toxic effects on bone cells (chemotherapy, phenytoin, or thiazolidinedions, which diverts mesenchymal stem cells from forming osteoblasts to forming adipocytes). However, besides effects on the mineralized matrix, interactions with collagen and other parts of the unmineralized matrix may decrease bone biomechanical competence in a manner that may not correlate with bone mineral density (BMD) measured by dual energy absorptiometry (DXA).Some drugs and drug classes may decrease BMD like the thiazolidinediones and consequently increase fracture risk. Other drugs such as glucocorticoids may decrease BMD, and thus increase fracture risk. However, glucocorticoids may also interfere with the unmineralized matrix leading to an increase in fracture risk, not mirrored in BMD changes. Some drugs such as selective serotonin reuptake inhibitors (SSRI), paracetamol, and non-steroidal anti-inflammatory drugs (NSAIDs) may not per se be associated with bone loss, but fracture risk may be increased, possibly stemming from an increased risk of falls stemming from effects on postural balance mediated by effects on the central nervous system or cardiovascular system.This paper performs a systematic review of drugs inducing bone loss or associated with fracture risk. The chapter is organized by the Anatomical Therapeutic Chemical (ATC) classification.
Topics: Bone Density; Bone and Bones; Fractures, Bone; Humans; Medroxyprogesterone Acetate; Pharmaceutical Preparations
PubMed: 31889220
DOI: 10.1007/164_2019_340 -
The Cochrane Database of Systematic... Nov 2019Many hormonal contraceptives have been associated with changes in carbohydrate metabolism. Alterations may include decreased glucose tolerance and increased insulin... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many hormonal contraceptives have been associated with changes in carbohydrate metabolism. Alterations may include decreased glucose tolerance and increased insulin resistance, which are risk factors for Type 2 diabetes mellitus and cardiovascular disease. These issues have been raised primarily with contraceptives containing estrogen.
OBJECTIVES
To evaluate the effect of hormonal contraceptives on carbohydrate metabolism in healthy women and those at risk for diabetes due to overweight.
SEARCH METHODS
In April 2014, we searched the computerized databases MEDLINE, POPLINE, CENTRAL, and LILACS for studies of hormonal contraceptives and carbohydrate metabolism. We also searched for clinical trials in ClinicalTrials.gov and ICTRP. The initial search also included EMBASE.
SELECTION CRITERIA
All randomized controlled trials were considered if they examined carbohydrate metabolism in women without diabetes who used hormonal contraceptives for contraception. Comparisons could be a placebo, a non-hormonal contraceptive, or another hormonal contraceptive that differed in drug, dosage, or regimen. Interventions included at least three cycles. Outcomes included glucose and insulin measures.
DATA COLLECTION AND ANALYSIS
We assessed all titles and abstracts identified during the literature searches. The data were extracted and entered into RevMan. We wrote to researchers for missing data. For continuous variables, the mean difference (MD) was computed with 95% confidence interval (CI) using a fixed-effect model. For dichotomous outcomes, the Peto odds ratio with 95% CI was calculated.
MAIN RESULTS
We found 31 trials that met the inclusion criteria. No new trials were eligible in 2014. Twenty-one trials compared combined oral contraceptives (COCs); others examined different COC regimens, progestin-only pills, injectables, a vaginal ring, and implants. None included a placebo. Of 34 comparisons, eight had any notable difference between the study groups in an outcome. Twelve trials studied desogestrel-containing COCs, and the few differences from levonorgestrel COCs were inconsistent. A meta-analysis of two studies showed the desogestrel group had a higher mean fasting glucose (MD 0.20; 95% CI 0.00 to 0.41). Where data could not be combined, single studies showed lower mean fasting glucose (MD -0.40; 95% CI -0.72 to -0.08) and higher means for two-hour glucose response (MD 1.08; 95% CI 0.45 to 1.71) and insulin area under the curve (AUC) (MD 20.30; 95% CI 4.24 to 36.36). Three trials examined the etonogestrel vaginal ring and one examined an etonogestrel implant. One trial showed the ring group had lower mean AUC insulin than the levonorgestrel-COC group (MD -204.51; 95% CI -389.64 to -19.38). Of eight trials of norethisterone preparations, five compared COCs and three compared injectables. In a COC trial, a norethisterone group had smaller mean change in glucose two-hour response than a levonorgestrel-COC group (MD -0.30; 95% CI -0.54 to -0.06). In an injectable study, a group using depot medroxyprogesterone acetate had higher means than the group using norethisterone enanthate for fasting glucose (MD 10.05; 95% CI 3.16 to 16.94), glucose two-hour response (MD 17.00; 95% CI 5.67 to 28.33), and fasting insulin (MD 3.40; 95% CI 2.07 to 4.73). Among five recent trials, two examined newer COCs with different estrogen types. One showed the group with nomegestrel acetate plus 17β-estradiol had lower means than the levonorgestrel group for incremental AUC glucose (MD -1.43; 95% CI -2.55 to -0.31) and glycosylated hemoglobin (HbA1c) (MD -0.10; 95% CI -0.18 to -0.02). Two trials compared extended versus conventional (cyclic) regimens. With a dienogest COC, an extended-use group had greater mean change in AUC glucose (MD 82.00; 95% CI 10.72 to 153.28). In a small trial using two levonorgestrel COCs, the lower-dose group showed smaller mean change in fasting glucose (MD -3.00; 95% CI -5.89 to -0.11), but the obese and normal weight women did not differ significantly.
AUTHORS' CONCLUSIONS
Current evidence suggests no major differences in carbohydrate metabolism between different hormonal contraceptives in women without diabetes. We cannot make strong statements due to having few studies that compared the same types of contraceptives. Many trials had small numbers of participants and some had large losses. Many of the earlier studies had limited reporting of methods. We still know very little about women at risk for metabolic problems due to being overweight. More than half of the trials had weight restrictions as inclusion criteria. Only one small trial stratified the groups by body mass index (obese versus normal).
Topics: Blood Glucose; Carbohydrate Metabolism; Contraception; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Dietary Carbohydrates; Fasting; Female; Humans; Insulin; Overweight; Randomized Controlled Trials as Topic
PubMed: 31711271
DOI: 10.1002/14651858.CD006133.pub5