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European Journal of Endocrinology Jul 2021It has been suggested that adverse early life exposures increase the risk of developing polycystic ovary syndrome (PCOS) in later life. We hypothesized that women born...
OBJECTIVE
It has been suggested that adverse early life exposures increase the risk of developing polycystic ovary syndrome (PCOS) in later life. We hypothesized that women born preterm would have more biochemical and clinical signs of PCOS than women born at term.
DESIGN
The ESTER Preterm Birth Study participants were born in Northern Finland and identified from the Northern Finland Birth Cohort and the Finnish Medical Birth Register. Altogether, 74 women born very or moderately preterm (<34 gestational weeks, VMPT), 127 born late preterm (at 34-36 weeks, LPT), and 184 born full term (≥37 weeks, controls) were included in the analysis (mean age: 23.2 years).
METHODS
We measured serum total testosterone and sex hormone-binding globulin (SHBG) and calculated the free androgen index (FAI). PCOS according to the clinical and biochemical signs was defined either as hirsutism and oligoamenorrhea (via questionnaire) or as oligoamenorrhea and elevated testosterone levels (>2.4 nmol/L).
RESULTS
Women born VMPT/LPT exhibited 33.0% (8.7, 62.8)/16.4% (-2.0, 38.1) higher testosterone, 28.5% (5.3, 45.9)/24.1% (5.6, 38.9) lower SHBG levels, and 64.6% (19.4, 127.1)/42.5% (11.1, 82.9) higher FAI than controls after adjusting for age and recruitment cohort, maternal BMI, smoking, and pregnancy disorders, parental education, history of hypertension, diabetes, myocardial infarction or stroke, and subject's birth weight s.d. Odds ratios for having PCOS were 1.67 (0.44, 6.23)/3.11 (1.26, 7.70).
CONCLUSIONS
Women born preterm have a more hyperandrogenic hormonal profile, and those born LPT are approximately three times more likely at risk to have PCOS compared to women born at term.
Topics: Adult; Adult Children; Androgens; Biomarkers; Body Mass Index; Case-Control Studies; Female; Finland; Gestational Age; Hirsutism; Humans; Infant, Newborn; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Complications; Premature Birth; Prenatal Exposure Delayed Effects; Risk Factors; Testosterone; Young Adult
PubMed: 34081616
DOI: 10.1530/EJE-20-1462 -
The Western Journal of Medicine Dec 1996Hirsutism is a common medical condition that in most women is due to the polycystic ovary syndrome or is idiopathic. For a few women, hirsutism signals a serious... (Review)
Review
Hirsutism is a common medical condition that in most women is due to the polycystic ovary syndrome or is idiopathic. For a few women, hirsutism signals a serious underlying disorder such as an ovarian or adrenal tumor, congenital adrenal hyperplasia, or Cushing's syndrome. A detailed medical history and examination can identify women in whom a serious disease is suspected and for whom laboratory evaluation is warranted. Measurements of serum testosterone, dehydroepiandrosterone, and 17 alpha-hydroxyprogesterone levels, and 24-hour urinary cortisol concentrations are important screening tests. Therapy is directed at suppressing ovarian or adrenal androgen production, inhibiting the conversion of testosterone to dihydrotestosterone, or antagonizing the effects of androgens at the receptor level.
Topics: 17-alpha-Hydroxyprogesterone; Cushing Syndrome; Dehydroepiandrosterone; Female; Hirsutism; Humans; Hydrocortisone; Polycystic Ovary Syndrome; Testosterone
PubMed: 9000866
DOI: No ID Found -
American Journal of Physiology.... Jan 2012This career retrospective describes how the initial work on the mechanism of hormone action provided the tools for the study of hirsutism, virilism, and polycystic... (Review)
Review
This career retrospective describes how the initial work on the mechanism of hormone action provided the tools for the study of hirsutism, virilism, and polycystic ovarian disease. After excessive ovarian and or adrenal androgen secretion in polycystic ovarian disease had been established, the question whether the disease was genetic or acquired, methods to manage hirsutism and methods for the induction of ovulation were addressed. Recognizing that steroid gonadotropin feedback was an important regulatory factor, initial studies were done on the secretion of LH and FSH in the ovulatory cycle. This was followed by the study of basic mechanisms of steroid-gonadotropin feedback system, using castration and steroid replacement and the events surrounding the natural onset of puberty. Studies in ovariectomized rats showed that progesterone was a pivotal enhancer of estrogen-induced gonadotropin release, thus accounting for the preovulatory gonadotropin surge. The effects of progesterone were manifested by depletion of the occupied estrogen receptors of the anterior pituitary, release of hypothalamic LHRH, and inhibition of enzymes that degrade LHRH. Progesterone also promoted the synthesis of FSH in the pituitary. The 3α,5α-reduced metabolite of progesterone brought about selective LH release and acted using the GABA(A) receptor system. The 5α-reduced metabolite of progesterone brought about selective FSH release; the ability of progesterone to bring about FSH release was dependent on its 5α-reduction. The GnRH neuron does not have steroid receptors; the steroid effect was shown to be mediated through the excitatory amino acid glutamate, which in turn stimulated nitric oxide. These observations led to the replacement of the long-accepted belief that ovarian steroids acted directly on the GnRH neuron by the novel concept that the steroid feedback effect was exerted at the glutamatergic neuron, which in turn regulated the GnRH neuron. The neuroprotective effects of estrogens on brain neurons are of considerable interest.
Topics: Androgens; Animals; Astrocytes; Estrogens; Excitatory Amino Acids; Feedback, Physiological; Female; Follicle Stimulating Hormone; Gonadotropins; Hirsutism; Hormone Replacement Therapy; Hormones; Humans; Hypothalamus; Luteinizing Hormone; Ovulation Induction; Polycystic Ovary Syndrome; Progesterone; Virilism
PubMed: 22028409
DOI: 10.1152/ajpendo.00488.2011 -
BMC Nephrology Feb 2017IgA nephropathy is the most common progressive glomerular disease to end stage renal failure worldwide. Calcineurin inhibitors (CNIs) is a selective immunosuppressant... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
IgA nephropathy is the most common progressive glomerular disease to end stage renal failure worldwide. Calcineurin inhibitors (CNIs) is a selective immunosuppressant widely used in organ transplantation. The efficacy and safety of calcineurin inhibitors for the treatment of IgA nephropathy remain uncertain.
METHODS
We performed a systematic literature search using the PubMed, Embase, Science Citation Index, Ovid evidence-based medicine, Chinese Biomedical Literature (CBM) and Chinese science and technology periodicals (CNKI, VIP, and Wan Fang) for randomized, controlled trials of CNIs therapy of IgA nephropathy. Complete remission rate (CR) was defined as proteinuria less than 0.5 or 0.3 g/d. Partial remission rate (PR) was defined as proteinuria reduced to at least half of the baseline measurement and an absolute value of >0.5 or 0.3 g/d.
RESULTS
Seven relevant trials were conducted with 374 patients enrolled. CNIs plus medium/low-dose steroid had a higher CR (RR = 2.51 [95% CI,1.25 to 5.04], P = 0.02) compared to therapy with steroid alone or placebo, but were not significant on PR (RR = 0.87 [95% CI,0.32 to 2.38]; P = 0.78). Also, significant alterations were observed in proteinuria (weighted mean difference, -0.46 g/d,[95% CI:-0.55 to -0.24], P < 0.01) with no differences were found in serum creatinine (SCr) (weighted mean difference, 0.57,95% CI:-4.05 to 5.19; P = 0.78) and estimated glomerular filtration rate (eGFR) (weighted mean difference, 1.13,95% CI:-4.05 to 6.32; P = 0.34) level between the two groups. CNI therapy was associated with an increased risk for adverse events (RR = 2.21,95% CI:1.52 to 3.21, P < 0.01), such as gastrointestinal and neurological symptoms or hirsutism.
CONCLUSIONS
CNIs might provide renal protection in patients with IgAN, but at an increased risk of adverse events. Reliably defining the efficacy and safety of CNIs in IgAN requires a high-quality trial with a large sample size.
Topics: Calcineurin Inhibitors; Causality; Drug-Related Side Effects and Adverse Reactions; Female; Gastrointestinal Diseases; Glomerulonephritis, IGA; Hirsutism; Humans; Immunosuppressive Agents; Male; Nervous System Diseases; Prevalence; Risk Factors; Treatment Outcome
PubMed: 28193247
DOI: 10.1186/s12882-017-0467-z -
Archives of Gynecology and Obstetrics Jan 2021Elevated concentrations of circulating testosterone are present in hyperreactio luteinalis (HL), a pregnancy-specific, self-limited condition. HL is associated with...
BACKGROUND
Elevated concentrations of circulating testosterone are present in hyperreactio luteinalis (HL), a pregnancy-specific, self-limited condition. HL is associated with maternal virilization in about 30% of cases. The correlation between testosterone levels and maternal virilization has not yet been quantified. Our aim was to identify a testosterone cut-off level which may allow to predict maternal virilization.
METHODS
A literature research was performed. Publications were chosen if serum testosterone concentrations and presence or absence of maternal virilization was mentioned. Additionally, we report serial levels of steroids analyzed by Liquid chromatography-tandem mass spectrometry (LC-MS/MS) in one case of HL managed at our institution.
RESULTS
In all, 31 cases fulfilled the search criteria. We found significant overlap between testosterone levels in asymptomatic women and women with signs of virilization (range 6.2-37.3 nmol/l and 13.7-197.5 nmol/l, respectively). The method applied for testosterone analysis was mentioned in three reports only. Peak serum testosterone concentration in our case was 120.3 nmol/l.
CONCLUSION
From the available data, maternal virilization in HL cannot be predicted by the level of circulating testosterone. However, comparability of results is hampered by the analytical methods applied. LC-MS/MS should preferably be used for reporting concentrations of circulating testosterone.
Topics: Adult; Chromatography, Liquid; Female; Humans; Ovarian Cysts; Pregnancy; Pregnancy Complications; Tandem Mass Spectrometry; Testosterone; Virilism
PubMed: 32815025
DOI: 10.1007/s00404-020-05745-6 -
Epigenetics Dec 2023Research suggests that polycystic ovary syndrome (PCOS) traits (e.g., hyperandrogenism) may create a suboptimal intrauterine environment and induce epigenetic...
Research suggests that polycystic ovary syndrome (PCOS) traits (e.g., hyperandrogenism) may create a suboptimal intrauterine environment and induce epigenetic modifications. Therefore, we assessed the associations of PCOS traits with neonatal DNA methylation (DNAm) using two independent cohorts. DNAm was measured in both cohorts using the Infinium MethylationEPIC array. Multivariable robust linear regression was used to determine associations of maternal PCOS exposure or preconception testosterone with methylation β-values at each CpG probe and corrected for multiple testing by false-discovery rate (FDR). In the birth cohort, 12% (102/849) had a PCOS diagnosis (8.1% PCOS without hirsutism; 3.9% PCOS with hirsutism). Infants exposed to maternal PCOS with hirsutism compared to no PCOS had differential DNAm at cg02372539 [β(SE): -0.080 (0.010); FDR = 0.009], cg08471713 [β(SE):0.077 (0.014); FDR = 0.016] and cg17897916 [β(SE):0.050 (0.009); FDR = 0.009] with adjustment for maternal characteristics including pre-pregnancy BMI. PCOS with hirsutism was also associated with 8 differentially methylated regions (DMRs). PCOS without hirsutism was not associated with individual CpGs. In an independent preconception cohort, total testosterone concentrations were associated with 3 DMRs but not with individual CpGs, though the top quartile of testosterone compared to the lowest was marginally associated with increased DNAm at cg21472377 near an uncharacterized locus (FDR = 0.09). Examination of these probes and DMRs indicate they may be under foetal genetic control. Overall, we found several associations among newborns exposed to PCOS, specifically when hirsutism was reported, and among newborns of women with relatively higher testosterone around conception.
Topics: Pregnancy; Infant; Humans; Infant, Newborn; Female; Polycystic Ovary Syndrome; Hirsutism; DNA Methylation; Hyperandrogenism; Testosterone
PubMed: 37992405
DOI: 10.1080/15592294.2023.2282319 -
Journal of Women's Health (2002) Nov 2021Hirsutism is the most common clinical symptom of hyperandrogenism, but racial and ethnic-specific thresholds have not been established. Our objective was to...
Hirsutism is the most common clinical symptom of hyperandrogenism, but racial and ethnic-specific thresholds have not been established. Our objective was to characterize hirsutism using self-report of hair growth in a large sample of African American women. The Study of Environment, Lifestyle, and Fibroids is a prospective community-based cohort study of African American women (23-34 at recruitment). A total of 1568 participants received the modified Ferriman-Gallwey (mFG) pictorial assessment and were asked if they were ever bothered by excess hair. We estimated the prevalence of hirsutism (mFG score ≥8) and associations of acne, polycystic ovary syndrome (PCOS), and menstrual cycle characteristics with hirsutism. We also explored hirsutism defined by the 95th percentile of scores in our cohort (mFG = 11) and a newly recommended criterion, mFG = 4. We could determine hirsutism status in 1556 women. Thirty-seven percent reported being bothered by excess hair, and 10% met the mFG criterion for hirsutism. History of severe facial acne was positively associated with hirsutism (prevalence ratio: 1.90; 95% confidence interval [CI]: 1.30-2.76), as was physician-diagnosed PCOS (2.22, 95% CI: 1.30-3.81). Women with irregular menstrual cycles were also more likely to report hirsutism (1.78, 95% CI: 1.00-3.18). Results were similar using mFG ≥11 and attenuated using mFG ≥4. Hirsutism prevalence was 10% in this community sample of African American women and was associated with PCOS, severe acne, and irregular menstrual cycles suggesting this represented hirsutism caused by hyperandrogenism. Ethnically diverse, population-based studies assessing the association between mFG score and androgen levels are needed to better understand the hirsutism threshold as a clinical marker of hyperandrogenism.
Topics: Adult; Black or African American; Cohort Studies; Female; Hirsutism; Humans; Polycystic Ovary Syndrome; Prevalence; Prospective Studies
PubMed: 34520248
DOI: 10.1089/jwh.2021.0125 -
International Braz J Urol : Official... 202146,XX Congenital adrenal hyperplasia (CAH) remains the first cause of genital virilization and current surgical techniques aim to restore female aspect of genitalia...
INTRODUCTION
46,XX Congenital adrenal hyperplasia (CAH) remains the first cause of genital virilization and current surgical techniques aim to restore female aspect of genitalia while preserving dorsal neurovascular bundle but not at the expense of not preserving erectile tissue. We aim to report our experience with a new surgical technique for clitoroplasty, completely preserving corporeal bodies, neurovascular bundles without dismembering the clitoris, in four patients with over a year follow up.
MATERIALS AND METHODS
After IRB approval four patients with 46,XX CAH and Prader 5 and 3 external genitalia, underwent feminizing genitoplasty. Complete preservation of erectile tissue was accomplished without a need to dissect dorsal neurovascular bundle. Glans size allowed no need for glanular reduction and there was no need to dismember the corporeal bodies.
RESULTS
Four patients 12 to 24-months-old underwent complete corporeal preservation clitoroplasty (CCPC), mean age was 18.5 months, mean follow up was 10.25 months. Vaginoplasty was performed in all patients with partial urogenital mobilization (PUM) and Urogenital Sinus flap (UF), only one severely virilized patient required a parasagittal pre-rectal approach to mobilize the vagina. We had no complications until last follow up.
CONCLUSION
To our knowledge, we are introducing the concept of CCPC without the need of disassembling the corporeal bodies, neurovascular bundle and glans. It stands as a new alternative for feminizing genitoplasty with complete preservation of erectile tissue and no dissection of neurovascular bundle. Although there is still lacking long-term follow-up, it represents a new step in conservative reconfiguration of the external virilized female genitalia.
Topics: Child, Preschool; Female; Humans; Infant; Adrenal Hyperplasia, Congenital; Clitoris; Genitalia, Female; Plastic Surgery Procedures; Surgical Flaps; Vagina; Virilism
PubMed: 33848081
DOI: 10.1590/S1677-5538.IBJU.2020.0839 -
Journal of Ayub Medical College,... 2021One of the leading causes of infertility in child bearing age females is polycystic ovary syndrome. It is characterized by altered hormonal profile causing androgen...
BACKGROUND
One of the leading causes of infertility in child bearing age females is polycystic ovary syndrome. It is characterized by altered hormonal profile causing androgen excess and insulin resistance which eventually leads to decreased ovulation rate.
METHODS
This was a crosssectional study that included 40 polycystic ovary syndrome (PCOS) patients and 40 infertility patients that did not have polycystic ovary syndrome determined by sonography and clinical features through quota sampling technique. Serum Total Testosterone and Sex Hormone Binding Globulin Levels were assayed. Using these two parameters, Free Androgen Index was calculated. Body Mass Index and central obesity was also determined.
RESULTS
Total Testosterone, Free Androgen Index and Body Mass Index were raised in PCOS group as indicated by p-value <0.05. Hirsutism was present in PCOS group (p-value <0.05). Sex Hormone Binding Globulin Levels were decreased in PCOS patients (p-value <0.05) but were within the lower half of normal range.
CONCLUSIONS
Levels of Sex Hormone Binding Globulin were decreased in PCOS cases and Free Androgen Index can help in better determining hyperandrogenaemia than total testosterone alone.
Topics: Androgens; Body Mass Index; Female; Hirsutism; Humans; Hyperandrogenism; Infertility; Polycystic Ovary Syndrome; Testosterone
PubMed: 35124911
DOI: No ID Found -
The Journal of Investigative Dermatology Jul 1993During the past decade we have examined both the therapeutic and the prophylactic effects of several agents on the macaque model of androgenetic alopecia. Minoxidil and... (Review)
Review
During the past decade we have examined both the therapeutic and the prophylactic effects of several agents on the macaque model of androgenetic alopecia. Minoxidil and diazoxide, potent hypotensive agents acting as peripheral vasodilators, are known to have a hypertrichotic side effect. Topical use of both agents induced significant hair regrowth in the bald scalps of macaques. The application of a steroid 5 alpha-reductase inhibitor (4MA) in non-bald preadolescent macaques has prevented baldness, whereas controls developed it during 2 years of treatment. The effects of hair growth were determined by 1) phototrichogram, 2) folliculogram (micro-morphometric analysis), and 3) the rate of DNA synthesis in the follicular cells. These effects were essentially a stimulation of the follicular cell proliferation, resulting in an enlargement of the anagen follicles from vellus to terminal type (therapy) or a maintenance of the prebald terminal follicles (prevention). A copper binding peptide (PC1031) had the effect of follicular enlargement on the back skin of fuzzy rats, covering the vellus follicles; the effect was similar to that of topical minoxidil. Analyzing the quantitative sequences of follicular size and cyclic phases, we speculate on the effect of agents on follicular growth. We also discuss the triggering mechanism of androgen in the follicular epithelial-mesenchymal (dermal papilla) interaction.
Topics: Animals; Cell Communication; Epithelial Cells; Hair; Hirsutism; Hypertrichosis; Macaca; Peptides; Rats; Rats, Mutant Strains; Skin
PubMed: 8326148
DOI: 10.1111/1523-1747.ep12363275