-
International Journal of Molecular... Nov 2022Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Despite its incidence, the syndrome is poorly understood and remains... (Review)
Review
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Despite its incidence, the syndrome is poorly understood and remains underdiagnosed, and female patients are diagnosed with a delay. The heterogenous nature of this complex disorder results from the combined occurrence of genetic, environmental, endocrine, and behavioral factors. Primary clinical manifestations of PCOS are derived from the excess of androgens (anovulation, polycystic ovary morphology, lack of or scanty, irregular menstrual periods, acne and hirsutism), whereas the secondary manifestations include multiple metabolic, cardiovascular, and psychological disorders. Dietary and lifestyle factors play important roles in the development and course of PCOS, which suggests strong epigenetic and environmental influences. Many studies have shown a strong association between PCOS and chronic, low-grade inflammation both in the ovarian tissue and throughout the body. In the vast majority of PCOS patients, elevated values of inflammatory markers or their gene markers have been reported. Development of the vicious cycle of the chronic inflammatory state in PCOS is additionally stimulated by hyperinsulinemia and obesity. Changes in DNA methylation, histone acetylation and noncoding RNA levels are presented in this review in the context of oxidative stress, reactive oxygen species, and inflammatory signaling in PCOS. Epigenetic modulation of androgenic activity in response to inflammatory signaling is also discussed.
Topics: Female; Humans; Polycystic Ovary Syndrome; Hirsutism; Anovulation; Androgens; Hyperinsulinism
PubMed: 36498989
DOI: 10.3390/ijms232314663 -
BMJ (Clinical Research Ed.) Sep 2003
Review
Topics: Anovulation; Body Weight; Electrocoagulation; Female; Hormones; Humans; Hyperprolactinemia; Hypogonadism; Hypothyroidism; Infertility, Female; Menopause, Premature; Ovulation Induction; Polycystic Ovary Syndrome
PubMed: 12958117
DOI: 10.1136/bmj.327.7414.546 -
Revista Da Associacao Medica Brasileira... 2015anovulation is a major cause of female infertility, and polycystic ovary syndrome (PCOS) is the leading cause of anovulation. While undergoing drug-induced ovulation,... (Review)
Review
INTRODUCTION
anovulation is a major cause of female infertility, and polycystic ovary syndrome (PCOS) is the leading cause of anovulation. While undergoing drug-induced ovulation, women with PCOS usually have a satisfactory response recruiting follicles, but some are unable to recruit follicles or often produce an excessive number of follicles, which can result in ovarian hyper-stimulation syndrome and/or multiple pregnancy. Surgical laparoscopy with ovarian "drilling" may prevent or reduce the need for drug-induced ovulation.
OBJECTIVE
to identify the current indications of laparoscopic ovarian drilling and the best surgical technique.
METHOD
a review of the medical literature based on systematic search in the Medline, Lilacs and Cochrane databases, using as keywords laparoscopy, polycystic ovary syndrome, and drilling.
RESULTS
we found 105 articles in the literature, 27 of these highly relevant, describing findings on ovarian drilling.
CONCLUSION
laparoscopic drilling is indicated for patients with polycystic ovary syndrome with ovulatory resistance to the use of clomiphene citrate, body mass index less than 30 kg/m2 and preoperative luteinizing hormone above 10 IU/L. The preferred surgical technique should be the realization of 5 to 10 perforations on the surface of each ovary bilaterally using monopolar energy.
Topics: Anovulation; Body Mass Index; Clomiphene; Drug Resistance; Female; Fertility Agents, Female; Humans; Laparoscopy; Luteinizing Hormone; Polycystic Ovary Syndrome; Pregnancy
PubMed: 26841163
DOI: 10.1590/1806-9282.61.06.530 -
Pediatrics Dec 2015Consensus has recently been reached by international pediatric subspecialty societies that otherwise unexplained persistent hyperandrogenic anovulation using age- and... (Review)
Review
Consensus has recently been reached by international pediatric subspecialty societies that otherwise unexplained persistent hyperandrogenic anovulation using age- and stage-appropriate standards are appropriate diagnostic criteria for polycystic ovary syndrome (PCOS) in adolescents. The purpose of this review is to summarize these recommendations and discuss their basis and implications. Anovulation is indicated by abnormal uterine bleeding, which exists when menstrual cycle length is outside the normal range or bleeding is excessive: cycles outside 19 to 90 days are always abnormal, and most are 21 to 45 days even during the first postmenarcheal year. Continued menstrual abnormality in a hyperandrogenic adolescent for 1 year prognosticates at least 50% risk of persistence. Hyperandrogenism is best indicated by persistent elevation of serum testosterone above adult norms as determined in a reliable reference laboratory. Because hyperandrogenemia documentation can be problematic, moderate-severe hirsutism constitutes clinical evidence of hyperandrogenism. Moderate-severe inflammatory acne vulgaris unresponsive to topical treatment is an indication to test for hyperandrogenemia. Treatment of PCOS is symptom-directed. Cyclic estrogen-progestin oral contraceptives are ordinarily the preferred first-line medical treatment because they reliably improve both the menstrual abnormality and hyperandrogenism. First-line treatment of the comorbidities of obesity and insulin resistance is lifestyle modification with calorie restriction and increased exercise. Metformin in conjunction with behavior modification is indicated for glucose intolerance. Although persistence of hyperandrogenic anovulation for ≥2 years ensures the distinction of PCOS from physiologic anovulation, early workup is advisable to make a provisional diagnosis so that combined oral contraceptive treatment, which will mask diagnosis by suppressing hyperandrogenemia, is not unnecessarily delayed.
Topics: Adolescent; Anovulation; Diagnosis, Differential; Female; Guidelines as Topic; Humans; Hyperandrogenism; Insulin Resistance; Metabolic Syndrome; Polycystic Ovary Syndrome
PubMed: 26598450
DOI: 10.1542/peds.2015-1430 -
The Journal of Clinical Endocrinology... Sep 2013Adolescents are at high risk for menstrual dysfunction. The diagnosis of anovulatory disorders that may have long-term health consequences is too often delayed. (Review)
Review
CONTEXT
Adolescents are at high risk for menstrual dysfunction. The diagnosis of anovulatory disorders that may have long-term health consequences is too often delayed.
EVIDENCE ACQUISITION
A review of the literature in English was conducted, and data were summarized and integrated from the author's perspective.
MAIN FINDINGS
Normal adolescent anovulation causes only minor menstrual cycle irregularity: most cycles range from 21-45 days, even in the first postmenarcheal year, 90% by the fourth year. Approximately half of symptomatic menstrual irregularity is due to neuroendocrine immaturity, and half is associated with increased androgen levels. The former is manifest as aluteal or short/deficient luteal phase cycles and usually resolves spontaneously. The latter seems related to polycystic ovary syndrome because adolescent androgen levels are associated with adult androgens and ovulatory dysfunction, but data are sparse. Obesity causes hyperandrogenemia and, via unclear mechanisms, seems to suppress LH; it may mimic polycystic ovary syndrome. The role of pubertal insulin resistance in physiological adolescent anovulation is unclear. High-sensitivity gonadotropin and steroid assays, the latter by specialty laboratories, are necessary for accurate diagnosis of pubertal disorders. Polycystic ovaries are a normal ultrasonographic finding in young women and are associated with nearly 2-fold increased anti-Müllerian hormone levels. Oral contraceptives are generally the first-line treatment for ongoing menstrual dysfunction, and the effects of treatment are similar among preparations.
CONCLUSIONS
Menstrual cycle duration persistently outside 21-45 days in adolescents is unusual, and persistence ≥ 1 year suggests that disordered hypothalamic-pituitary-gonadal function be considered. Research is needed on the mechanisms and prognosis of adolescent anovulation.
Topics: Adolescent; Anovulation; Female; Humans; Menstrual Cycle; Menstruation Disturbances; Ovary; Pituitary Gland; Polycystic Ovary Syndrome
PubMed: 23913942
DOI: 10.1210/jc.2013-1770 -
American Family Physician Oct 1999The most probable etiology of abnormal uterine bleeding relates to the patient's reproductive age, as does the likelihood of serious endometrial pathology. The specific...
The most probable etiology of abnormal uterine bleeding relates to the patient's reproductive age, as does the likelihood of serious endometrial pathology. The specific diagnostic approach depends on whether the patient is premenopausal, perimenopausal or postmenopausal. In premenopausal women with normal findings on physical examination, the most likely diagnosis is dysfunctional uterine bleeding (DUB) secondary to anovulation, and the diagnostic investigation is targeted at identifying the etiology of anovulation. In perimenopausal patients, endometrial biopsy and other methods of detecting endometrial hyperplasia or carcinoma must be considered early in the investigation. Uterine pathology, particularly endometrial carcinoma, is common in postmenopausal women with abnormal uterine bleeding. Thus, in this age group, endometrial biopsy or transvaginal ultrasonography is included in the initial investigation. Premenopausal women with DUB may respond to oral contraceptives, cyclic medroxyprogesterone therapy or cyclic clomiphene. Perimenopausal women may also be treated with low-dose oral contraceptives or medroxyprogesterone. Erratic bleeding during hormone replacement therapy in postmenopausal women with no demonstrable pathology may respond to manipulation of the hormone regimen.
Topics: Algorithms; Anovulation; Female; Hormone Replacement Therapy; Humans; Menstruation Disturbances; Ovulation; Physical Examination; Postmenopause; Premenopause
PubMed: 10524483
DOI: No ID Found -
American Family Physician Apr 2004Abnormal uterine bleeding is a common presenting symptom in the family practice setting. In women of childbearing age, a methodical history, physical examination, and... (Review)
Review
Abnormal uterine bleeding is a common presenting symptom in the family practice setting. In women of childbearing age, a methodical history, physical examination, and laboratory evaluation may enable the physician to rule out causes such as pregnancy and pregnancy-related disorders, medications, iatrogenic causes, systemic conditions, and obvious genital tract pathology. Dysfunctional uterine bleeding (anovulatory or ovulatory) is diagnosed by exclusion of these causes. In women of childbearing age who are at high risk for endometrial cancer, the initial evaluation includes endometrial biopsy; saline-infusion sonohysterography or diagnostic hysteroscopy is performed if initial studies are inconclusive or the bleeding continues. Women of childbearing age who are at low risk for endometrial cancer may be assessed initially by transvaginal ultrasonography. Postmenopausal women with abnormal uterine bleeding should be offered dilatation and curettage; if they are poor candidates for general anesthesia or decline dilatation and curettage, they may be offered transvaginal ultrasonography or saline-infusion sonohysterography with directed endometrial biopsy. Medical management of anovulatory dysfunctional uterine bleeding may include oral contraceptive pills or cyclic progestins. Menorrhagia is managed most effectively with nonsteroidal anti-inflammatory drugs or the levonorgestrel intrauterine contraceptive device. Surgical management may include hysterectomy or less invasive, uterus-sparing procedures.
Topics: Adult; Algorithms; Anovulation; Diagnosis, Differential; Endometrial Neoplasms; Endometrium; Female; Humans; Hysterosalpingography; Hysteroscopy; Menorrhagia; Menstruation Disturbances; Middle Aged; Postmenopause; Premenopause; Risk Factors; Uterine Hemorrhage
PubMed: 15117012
DOI: No ID Found -
Paediatric and Perinatal Epidemiology Mar 2021Obesity, a body mass index (BMI) ≥30 kg/m , is linked to infertility, potentially through a greater risk of anovulation due to elevated androgens. Yet, previous... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Obesity, a body mass index (BMI) ≥30 kg/m , is linked to infertility, potentially through a greater risk of anovulation due to elevated androgens. Yet, previous studies have not directly assessed the impact of adiposity, or body fat, on anovulation in the absence of clinical infertility.
OBJECTIVE
To characterise the associations between adiposity and anovulation among women menstruating on a regular basis.
METHODS
Women from the EAGeR trial (n = 1200), a randomised controlled trial of low-dose aspirin and pregnancy loss among women trying to conceive, were used to estimate associations between adiposity and incident anovulation. Participants completed baseline questionnaires and anthropometry, and provided blood specimens. Women used fertility monitors for up to six consecutive menstrual cycles, with collection of daily first morning voids for hormone analysis in the first two menstrual cycles for prospective assessment of anovulation. Anovulation was assessed by urine pregnanediol glucuronide or luteinising hormone concentration or the fertility monitor. Weighted mixed-effects log-binomial regression was used to estimate associations between measures of adiposity and incident anovulation, adjusted for free (bioavailable) testosterone, anti-Mullerian hormone (AMH), serum lipids, and demographic and life style factors.
RESULTS
343 (28.3%) women experienced at least one anovulatory cycle. Anovulation risk was higher per kg/m greater BMI (relative risk [RR] 1.03, 95% confidence interval (CI) 1.01, 1.04), cm waist circumference (RR 1.01, 95% CI 1.00, 1.02), mm subscapular skinfold (RR 1.02, 95% CI 1.01, 1.03), and mm middle upper arm circumference (RR 1.04, 95% CI 1.01, 1.06) adjusted for serum free testosterone, AMH, lipids, and other factors.
CONCLUSIONS
Adiposity may be associated with anovulation through pathways other than testosterone among regularly menstruating women. This may account in part for reported associations between greater adiposity and infertility among women having menstrual cycles regularly. Understanding the association between adiposity and anovulation might lead to targeted interventions for preventing infertility.
Topics: Adiposity; Anovulation; Female; Humans; Obesity; Pregnancy; Prospective Studies; Testosterone
PubMed: 33107110
DOI: 10.1111/ppe.12726 -
BMJ (Clinical Research Ed.) Jan 2017To compare the effectiveness of alternative first line treatment options for women with WHO group II anovulation wishing to conceive. (Review)
Review
OBJECTIVE
To compare the effectiveness of alternative first line treatment options for women with WHO group II anovulation wishing to conceive.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Cochrane Central Register of Controlled Trials, Medline, and Embase, up to 11 April 2016.
STUDY SELECTION
Randomised controlled trials comparing eight ovulation induction treatments in women with WHO group II anovulation: clomiphene, letrozole, metformin, clomiphene and metformin combined, tamoxifen, gonadotropins, laparoscopic ovarian drilling, and placebo or no treatment. Study quality was measured on the basis of the methodology and categories described in the Cochrane Collaboration Handbook. Pregnancy, defined preferably as clinical pregnancy, was the primary outcome; live birth, ovulation, miscarriage, and multiple pregnancy were secondary outcomes.
RESULTS
Of 2631 titles and abstracts initially identified, 54 trials reporting on 7173 women were included. All pharmacological treatments were superior to placebo or no intervention in terms of pregnancy and ovulation. Compared with clomiphene alone, both letrozole and the combination of clomiphene and metformin showed higher pregnancy rates (odds ratio 1.69, 95% confidence interval 1.33 to 2.14; 1.71, 1.28 to 2.27; respectively). Letrozole led to higher live birth rates when compared with clomiphene alone (1.67, 1.11 to 2.49). Metformin led to lower multiple pregnancy rates compared with clomiphene alone (0.22, 0.05 to 0.93).
CONCLUSIONS
In women with WHO group II anovulation, letrozole and the combination of clomiphene and metformin are superior to clomiphene alone in terms of pregnancy. Compared with clomiphene alone, letrozole is the only treatment showing a significantly higher rate of live birth.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42015027579.
READERS' NOTE
This is the second version of this paper. The original version was corrected following the retraction of two studies and removal of another which were ineligible (references 40, 41, and 75 of the original paper). These studies are not shown in this version. A tracked changes version of the original version is attached as a supplementary file to the correction notice, which explains the issue further.
Topics: Anovulation; Clomiphene; Drug Therapy, Combination; Female; Humans; Infertility, Female; Letrozole; Metformin; Network Meta-Analysis; Nitriles; Ovulation Induction; Pregnancy; Pregnancy Rate; Treatment Outcome; Triazoles
PubMed: 28143834
DOI: 10.1136/bmj.j138 -
Journal of Pediatric and Adolescent... Dec 2015Polycystic ovary syndrome (PCOS) is the most common cause of chronic hyperandrogenic anovulation. Two-thirds of PCOS patients have functionally typical PCOS, with... (Review)
Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common cause of chronic hyperandrogenic anovulation. Two-thirds of PCOS patients have functionally typical PCOS, with typical functional ovarian hyperandrogenism manifest as 17-hydroxyprogesterone hyper-responsiveness to gonadotropin stimulation. Most, but not all, of the remainder have atypical functional ovarian hyperandrogenism. Many asymptomatic volunteers with polycystic ovary morphology (PCOM) have similar abnormalities.
OBJECTIVE
The objective of this paper is to review the relationship of biochemical ovarian function to the clinical spectrum observed in PCOS and in normal volunteers with PCOM.
FINDINGS
Adolescents and adults with PCOS are similar clinically and biochemically. Ninety-five percent of functionally typical PCOS have classic PCOS, ie, hyperandrogenic anovulation with PCOM. In addition to having more severe hyperandrogenism and a greater prevalence of PCOM than other PCOS, they have a significantly greater prevalence of glucose intolerance although insulin resistance is similarly reduced. Half of normal-variant PCOM have PCOS-related steroidogenic dysfunction, which suggests a PCOS carrier state.
CONCLUSIONS
There is a spectrum of ovarian androgenic dysfunction that ranges from subclinical hyperandrogenemia in some normal-variant PCOM to severe ovarian hyperandrogenism in most classic PCOS. A minority of mild PCOS cases do not fall on this spectrum of ovarian androgenic dysfunction, but rather seem to have obesity as the basis of their hyperandrogenism, or, less often, isolated adrenal androgenic dysfunction. Half of normal-variant PCOM also do not fall on the PCOS spectrum, and some of these seem to have excessive folliculogenesis as a variant that may confer mild prolongation of the reproductive lifespan. Improved understanding of PCOM in young women is needed.
Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adult; Anovulation; Female; Humans; Hyperandrogenism; Insulin Resistance; Ovary; Phenotype; Polycystic Ovary Syndrome
PubMed: 25840648
DOI: 10.1016/j.jpag.2014.07.016