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Anovulation

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Ian S Fraser – 1st expert on this subject based on the ideXlab platform

  • progestogens with or without oestrogen for irregular uterine bleeding associated with Anovulation
    Cochrane Database of Systematic Reviews, 2012
    Co-Authors: Martha Hickey, Jenny Higham, Ian S Fraser

    Abstract:

    Background
    Irregular menstrual bleeding may arise due to exogenous sex steroids, lesions of the genital tract or be associated with Anovulation. Irregular bleeding due to oligo/Anovulation (previously called dysfunctional uterine bleeding or DUB) is more common at the extremes of reproductive life, and in women with ovulatory disorders such as polycystic ovary syndrome (PCOS). In anovulatory cycles there may be prolonged oestrogen stimulation of the endometrium without progesterone withdrawal and so cycles are irregular and bleeding may be heavy. This is the rationale for using cyclical progestogens during the second half of the menstrual cycle, in order to provoke a regular withdrawal bleed. Continuous progestogen is intended to induce endometrial atrophy and hence to prevent oestrogen-stimulated endometrial proliferation. Progestogens, and oestrogens and progestogens in combination, are widely used in the management of irregular menstrual bleeding, but the regime, dose and type of progestogen used vary widely, with little consensus about the optimum treatment approach.

    Objectives
    To determine the effectiveness and acceptability of progestogens alone or in combination with oestrogens in the regulation of irregular menstrual bleeding associated with oligo/Anovulation.

    Search methods
    We searched the following databases in February 2012: Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and reference lists of articles.

    Selection criteria
    All randomised controlled trials of progestogens (via any route) alone or in combination with oestrogens in the treatment of irregular menstrual bleeding associated with oligo/Anovulation.

    Data collection and analysis
    Study quality assessment and data extraction were carried out independently by two review authors. All authors were experts in the content of this review.

    Main results
    No randomised trials were identified that compared progestogens with oestrogens and progestogens or with placebo in the management of irregular bleeding associated with oligo/Anovulation.

    Authors’ conclusions
    There is a paucity of randomised studies relating to the use of progestogens and of oestrogens and progestogens in combination in the treatment of irregular menstrual bleeding associated with Anovulation. There is no consensus about which regimens are most effective.  Further research is needed to establish the role of these hormonal treatments in the management of this common gynaecological problem.

  • The Cochrane Library – Progestogens with or without oestrogen for irregular uterine bleeding associated with Anovulation.
    Cochrane Database of Systematic Reviews, 2012
    Co-Authors: Martha Hickey, Jenny Higham, Ian S Fraser

    Abstract:

    Background
    Irregular menstrual bleeding may arise due to exogenous sex steroids, lesions of the genital tract or be associated with Anovulation. Irregular bleeding due to oligo/Anovulation (previously called dysfunctional uterine bleeding or DUB) is more common at the extremes of reproductive life, and in women with ovulatory disorders such as polycystic ovary syndrome (PCOS). In anovulatory cycles there may be prolonged oestrogen stimulation of the endometrium without progesterone withdrawal and so cycles are irregular and bleeding may be heavy. This is the rationale for using cyclical progestogens during the second half of the menstrual cycle, in order to provoke a regular withdrawal bleed. Continuous progestogen is intended to induce endometrial atrophy and hence to prevent oestrogen-stimulated endometrial proliferation. Progestogens, and oestrogens and progestogens in combination, are widely used in the management of irregular menstrual bleeding, but the regime, dose and type of progestogen used vary widely, with little consensus about the optimum treatment approach.

    Objectives
    To determine the effectiveness and acceptability of progestogens alone or in combination with oestrogens in the regulation of irregular menstrual bleeding associated with oligo/Anovulation.

    Search methods
    We searched the following databases in February 2012: Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and reference lists of articles.

    Selection criteria
    All randomised controlled trials of progestogens (via any route) alone or in combination with oestrogens in the treatment of irregular menstrual bleeding associated with oligo/Anovulation.

    Data collection and analysis
    Study quality assessment and data extraction were carried out independently by two review authors. All authors were experts in the content of this review.

    Main results
    No randomised trials were identified that compared progestogens with oestrogens and progestogens or with placebo in the management of irregular bleeding associated with oligo/Anovulation.

    Authors’ conclusions
    There is a paucity of randomised studies relating to the use of progestogens and of oestrogens and progestogens in combination in the treatment of irregular menstrual bleeding associated with Anovulation. There is no consensus about which regimens are most effective.  Further research is needed to establish the role of these hormonal treatments in the management of this common gynaecological problem.

  • progestogens versus oestrogens and progestogens for irregular uterine bleeding associated with Anovulation
    Cochrane Database of Systematic Reviews, 2007
    Co-Authors: Martha Hickey, Jenny Higham, Ian S Fraser

    Abstract:

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

Sunni L Mumford – 2nd expert on this subject based on the ideXlab platform

  • dietary minerals reproductive hormone levels and sporadic Anovulation associations in healthy women with regular menstrual cycles
    British Journal of Nutrition, 2018
    Co-Authors: Jean Wactawskiwende, Torie C Plowden, Karen C Schliep, Kara A Michels, Ellen N Chaljub, Sunni L Mumford

    Abstract:

    : Although minerals are linked to several reproductive outcomes, it is unknown whether dietary minerals are associated with ovulatory function. We hypothesised that low intakes of minerals would be associated with an increased risk of Anovulation. We investigated associations between dietary mineral intake and both reproductive hormones and Anovulation in healthy women in the BioCycle Study, which prospectively followed up 259 regularly menstruating women aged 18-44 years who were not taking mineral supplements for two menstrual cycles. Intakes of ten selected minerals were assessed through 24-h dietary recalls at up to four times per cycle in each participant. Oestradiol, progesterone, luteinising hormone (LH), follicle-stimulating hormone (FSH), sex-hormone-binding globulin and testosterone were measured in serum up to eight times per cycle. We used weighted linear mixed models to evaluate associations between minerals and hormones and generalised linear models for risk of Anovulation. Compared with Na intake ≥1500 mg, Na intake <1500 mg was associated with higher levels of FSH (21·3 %; 95 % CI 7·5, 36·9) and LH (36·8 %; 95 % CI 16·5, 60·5) and lower levels of progesterone (-36·9 %; 95 % CI -56·5, -8·5). Na intake <1500 mg (risk ratio (RR) 2·70; 95 % CI 1·00, 7·31) and Mn intake <1·8 mg (RR 2·00; 95 % CI 1·02, 3·94) were associated with an increased risk of Anovulation, compared with higher intakes, respectively. Other measured dietary minerals were not associated with ovulatory function. As essential minerals are mostly obtained via diet, our results comparing insufficient levels with sufficient levels highlight the need for future research on dietary nutrients and their associations with ovulatory cycles.

  • c reactive protein in relation to fecundability and Anovulation among eumenorrheic women
    Fertility and Sterility, 2018
    Co-Authors: Rose G Radin, Sunni L Mumford, Neil J Perkins, Lindsey A Sjaarda, Robert M Silver, Carrie Nobles, Brian D Wilcox, Anna Z Pollack, Karen C Schliep, Torie C Plowden

    Abstract:

    Objective To assess systemic inflammation in relation to fecundability and Anovulation. Design Prospective cohort study among participants in the Effects of Aspirin in Gestation and Reproduction trial who were assigned to the placebo. Setting Academic medical centers. Patient(s) Healthy eumenorrheic women (n = 572), 18–40 years of age, with one or two pregnancy losses, attempting spontaneous pregnancy. Intervention(s) Baseline serum high-sensitivity C-reactive protein (hsCRP) values Main Outcome Measure(s) Discrete Cox proportional hazards models estimated the fecundability odds ratio (FOR) and 95% confidence interval (CI) and adjusted for potential confounders. Log-binomial regression estimated the risk ratio (RR) and 95% CI of Anovulation. The algorithm to define Anovulation used data on urinary concentrations of hCG, pregnanediol-3-glucuronide, and LH as well as fertility monitor readings. Result(s) Higher hsCRP was associated with reduced fecundability but not with an increased risk of Anovulation. Conclusion(s) Among healthy women attempting pregnancy after one or two pregnancy losses, we found preliminary evidence that systemic inflammation is associated with reduced fecundability, but not independently from adiposity. Sporadic Anovulation did not appear to drive this association. Clinical Trial Registration Number ClinicalTrials.gov: NCT00467363.

  • dairy food intake is associated with reproductive hormones and sporadic Anovulation among healthy premenopausal women
    Journal of Nutrition, 2017
    Co-Authors: Jean Wactawskiwende, Torie C Plowden, Lindsey A Sjaarda, Kara A Michels, Ellen N Chaljub, Sunni L Mumford

    Abstract:

    Background: Dairy food intake has been associated with infertility; however, little is known with regard to associations with reproductive hormones or Anovulation.

    Objective: We investigated whether intakes of dairy foods and specific nutrients were associated with reproductive hormone concentrations across the cycle and the risk of sporadic Anovulation among healthy women.

    Methods: We prospectively measured serum reproductive hormones ≤8 times/menstrual cycle for 2 cycles from 259 regularly menstruating women (mean age: 27.3 y). Dairy food intake was assessed via 24-h dietary recalls 4 times/cycle. Dairy food intakes were assessed by 1) total and low- and high-fat dairy products; 2) dairy nutrients, including fat, lactose, calcium, and phosphorus; and 3) dairy foods, including milk, cheese, butter, cream, yogurt, and ice cream categories. Weighted linear mixed models were used to evaluate associations between dairy nutrients or food intakes and hormone concentrations. Modified Poisson regression models with robust error variance were used to evaluate Anovulation. Models were adjusted for age, body mass index, race, physical activity, Mediterranean diet score, total energy, protein, fiber, caffeine, and other hormones.

    Results: Each serving increase in total and low- and high-fat dairy foods and all increases in amounts of all dairy nutrients tested were associated with an ∼5% reduction in serum estradiol concentrations but were not associated with Anovulation. Total and high-fat dairy food intakes were positively associated with serum luteinizing hormone concentrations. We observed associations between intakes of >0 servings of yogurt (RR: 2.1; 95% CI: 1.2, 3.7) and cream (RR: 1.8; 95% CI: 1.0, 3.2) and a higher risk of sporadic Anovulation compared with no intake.

    Conclusions: Our study showed associations between increasing dairy food and nutrient intakes and decreasing estradiol concentrations as well as between cream and yogurt intakes and the risk of sporadic Anovulation. These results highlight the potential role of dairy in reproductive function in healthy women.

Jean Wactawskiwende – 3rd expert on this subject based on the ideXlab platform

  • dietary minerals reproductive hormone levels and sporadic Anovulation associations in healthy women with regular menstrual cycles
    British Journal of Nutrition, 2018
    Co-Authors: Jean Wactawskiwende, Torie C Plowden, Karen C Schliep, Kara A Michels, Ellen N Chaljub, Sunni L Mumford

    Abstract:

    : Although minerals are linked to several reproductive outcomes, it is unknown whether dietary minerals are associated with ovulatory function. We hypothesised that low intakes of minerals would be associated with an increased risk of Anovulation. We investigated associations between dietary mineral intake and both reproductive hormones and Anovulation in healthy women in the BioCycle Study, which prospectively followed up 259 regularly menstruating women aged 18-44 years who were not taking mineral supplements for two menstrual cycles. Intakes of ten selected minerals were assessed through 24-h dietary recalls at up to four times per cycle in each participant. Oestradiol, progesterone, luteinising hormone (LH), follicle-stimulating hormone (FSH), sex-hormone-binding globulin and testosterone were measured in serum up to eight times per cycle. We used weighted linear mixed models to evaluate associations between minerals and hormones and generalised linear models for risk of Anovulation. Compared with Na intake ≥1500 mg, Na intake <1500 mg was associated with higher levels of FSH (21·3 %; 95 % CI 7·5, 36·9) and LH (36·8 %; 95 % CI 16·5, 60·5) and lower levels of progesterone (-36·9 %; 95 % CI -56·5, -8·5). Na intake <1500 mg (risk ratio (RR) 2·70; 95 % CI 1·00, 7·31) and Mn intake <1·8 mg (RR 2·00; 95 % CI 1·02, 3·94) were associated with an increased risk of Anovulation, compared with higher intakes, respectively. Other measured dietary minerals were not associated with ovulatory function. As essential minerals are mostly obtained via diet, our results comparing insufficient levels with sufficient levels highlight the need for future research on dietary nutrients and their associations with ovulatory cycles.

  • dairy food intake is associated with reproductive hormones and sporadic Anovulation among healthy premenopausal women
    Journal of Nutrition, 2017
    Co-Authors: Jean Wactawskiwende, Torie C Plowden, Lindsey A Sjaarda, Kara A Michels, Ellen N Chaljub, Sunni L Mumford

    Abstract:

    Background: Dairy food intake has been associated with infertility; however, little is known with regard to associations with reproductive hormones or Anovulation.

    Objective: We investigated whether intakes of dairy foods and specific nutrients were associated with reproductive hormone concentrations across the cycle and the risk of sporadic Anovulation among healthy women.

    Methods: We prospectively measured serum reproductive hormones ≤8 times/menstrual cycle for 2 cycles from 259 regularly menstruating women (mean age: 27.3 y). Dairy food intake was assessed via 24-h dietary recalls 4 times/cycle. Dairy food intakes were assessed by 1) total and low- and high-fat dairy products; 2) dairy nutrients, including fat, lactose, calcium, and phosphorus; and 3) dairy foods, including milk, cheese, butter, cream, yogurt, and ice cream categories. Weighted linear mixed models were used to evaluate associations between dairy nutrients or food intakes and hormone concentrations. Modified Poisson regression models with robust error variance were used to evaluate Anovulation. Models were adjusted for age, body mass index, race, physical activity, Mediterranean diet score, total energy, protein, fiber, caffeine, and other hormones.

    Results: Each serving increase in total and low- and high-fat dairy foods and all increases in amounts of all dairy nutrients tested were associated with an ∼5% reduction in serum estradiol concentrations but were not associated with Anovulation. Total and high-fat dairy food intakes were positively associated with serum luteinizing hormone concentrations. We observed associations between intakes of >0 servings of yogurt (RR: 2.1; 95% CI: 1.2, 3.7) and cream (RR: 1.8; 95% CI: 1.0, 3.2) and a higher risk of sporadic Anovulation compared with no intake.

    Conclusions: Our study showed associations between increasing dairy food and nutrient intakes and decreasing estradiol concentrations as well as between cream and yogurt intakes and the risk of sporadic Anovulation. These results highlight the potential role of dairy in reproductive function in healthy women.

  • serum caffeine and paraxanthine concentrations and menstrual cycle function correlations with beverage intakes and associations with race reproductive hormones and Anovulation in the biocycle study
    The American Journal of Clinical Nutrition, 2016
    Co-Authors: Enrique F. Schisterman, Neil J Perkins, Rose G Radin, Lindsey A Sjaarda, Karen C Schliep, Jean Wactawskiwende, Shvetha M Zarek, Emily M Mitchell, Sunni L Mumford

    Abstract:

    BACKGROUND: Clinicians often recommend limiting caffeine intake while attempting to conceive; however, few studies have evaluated the associations between caffeine exposure and menstrual cycle function, and we are aware of no previous studies assessing biological dose via well-timed serum measurements. OBJECTIVES: We assessed the relation between caffeine and its metabolites and reproductive hormones in a healthy premenopausal cohort and evaluated potential effect modification by race. DESIGN: Participants (n = 259) were followed for ≤2 menstrual cycles and provided fasting blood specimens ≤8 times/cycle. Linear mixed models were used to estimate associations between serum caffeine biomarkers and geometric mean reproductive hormones, whereas Poisson regression was used to assess risk of sporadic Anovulation. RESULTS: The highest compared with the lowest serum caffeine tertile was associated with lower total testosterone [27.9 ng/dL (95% CI: 26.7, 29.0 ng/dL) compared with 29.1 ng/dL (95% CI: 27.9, 30.3 ng/dL), respectively] and free testosterone [0.178 ng/mL (95% CI: 0.171, 0.185 ng/dL) compared with 0.186 ng/mL (95% CI: 0.179, 0.194 ng/dL), respectively] after adjustment for age, race, percentage of body fat, daily vigorous exercise, perceived stress, depression, dietary factors, and alcohol intake. The highest tertiles compared with the lowest tertiles of caffeine and paraxanthine were also associated with reduced risk of Anovulation [adjusted RRs (aRRs): 0.39 (95% CI: 0.18, 0.87) and 0.40 (95% CI: 0.18, 0.87), respectively]. Additional adjustment for self-reported coffee intake did not alter the reproductive hormone findings and only slightly attenuated the results for serum caffeine and paraxanthine and Anovulation. Although reductions in the concentrations of total testosterone and free testosterone and decreased risk of Anovulation were greatest in Asian women, there was no indication of effect modification by race. CONCLUSION: Caffeine intake, irrespective of the beverage source, may be associated with reduced testosterone and improved menstrual cycle function in healthy premenopausal women.