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PubMed2005

[Polycystic ovary syndrome. New pathophysiological discoveries--therapeutic consequences].

Polycystic ovary syndrome (PCOS) is characterised by anovulation, infertility and hyperandrogenism. The condition affects about 5-10% of women in the reproductive age group. Insulin resistance has proven to be a key factor in the pathogenesis of PCOS. There are several similarities between PCOS and the metabolic syndrome, and PCOS may be a risk factor for development of type 2 diabetes and cardiovascular disease. The treatment of PCOS has, so far, been focussed on treatment of the clinical signs and symptoms. Oral contraceptives have been the standard treatment. There is now a greater focus on the management of the metabolic consequences of PCOS, primarily through lifestyle intervention to achieve weight loss and increase physical activity. Metformin has proven to be effective in the management of the metabolic disturbances, anovulation and hirsutism and is now a widely accepted therapy. The thiazolidinediones (pio- and rosiglitazone), a novel class of insulin-sensitising agents, also seem to ameliorate the metabolic disturbances and clinical symptoms characterizing PCOS, but more randomised, controlled trials are needed before clinical guidelines can be determined.

Contraceptives, Oral↗
PubMed2005

Polycystic ovarian syndrome in Hong Kong Chinese women: patient characteristics and diagnostic criteria.

OBJECTIVES: To identify the characteristics of Hong Kong Chinese women with polycystic ovarian syndrome and to compare different diagnostic criteria. DESIGN: Retrospective study. SETTING: Gynae-endocrinology Clinics in the Prince of Wales Hospital, Hong Kong. PATIENTS: Ninety Hong Kong Chinese women with polycystic ovarian syndrome who were diagnosed according to the hospital's criteria. MAIN OUTCOME MEASURES: Prevalence of typical features of polycystic ovarian syndrome, including anovulation and hyperandrogenism (with other endocrine causes excluded), polycystic ovarian features on ultrasonography, luteinising hormone predominance, obesity, and insulin resistance. RESULTS: Almost all (98.9%) patients with polycystic ovarian syndrome presented with anovulation, only 48.9% of them had clinical or biochemical evidence of hyperandrogenism. Typical ultrasound appearances of polycystic ovaries were observed in 86.7% of patients. Luteinising hormone predominance and insulin resistance were demonstrated in 67.8% and 40.7% of the cohort, respectively. Eight-six (95.6%) patients should have also been diagnosed with polycystic ovarian syndrome based on the 2003 Rotterdam new criteria. About 60% of patients who screened positive for insulin resistance had normal fasting serum glucose levels. The same proportion who had full screening for insulin resistance by oral glucose tolerance tests and fasting serum glucose to insulin ratios had discordant results of these two tests. CONCLUSIONS: The 2003 Rotterdam new diagnostic criteria for polycystic ovarian syndrome are generally applicable to the Hong Kong Chinese population. Early detection of insulin resistance in patients with polycystic ovarian syndrome can be ensured by performing an oral glucose tolerance test combined with measurement of fasting serum glucose to insulin ratio.

Adult↗
PubMed2006

The frequency of insulin resistance calculated upon the basis of a fasting glucose to insulin ratio and characteristics of insulin resistant women with polycystic ovary syndrome.

BACKGROUND: The Polycystic Ovary Syndrome (PCOS) is a common endocrine and metabolic disorder of women of reproductive age, characterized by hyperandrogenism and chronic anovulation. Peripheral insulin resistance (IR) has a crucial role in the pathogenesis of this disorder. A fasting glucose to insulin (G/I) ratio is a simple, reliable, sensitive and specific measurement of insulin sensitivity and is a useful test for the identification of IR in women with PCOS, who have to be treated with insulin sensitizers. OBJECTIVE: To calculate the frequency of IR among patients with PCOS, using the fasting G/I ratio, and to compare the clinical and biochemical parameters between insulin-resistant and insulin-sensitive groups. PATIENTS AND METHODS: The study comprised 62 patients of reproductive age (18-40) with PCOS. The diagnosis PCOS was determined according to the diagnostic criteria from Rotterdam 2003, i.e. the presence of two of the following three criteria: oligo-ovulation and/or anovulation; clinical and/or biochemical hyperandrogenism; and polycystic ovaries. All other states associated with hyperandrogenism had been previously excluded. An inclusion criterion for the study was the body mass index (BMI) >or=25 (kg/m2). After calculating the fasting glucose(mg/dl) / insulin(microU/ml) ratio, the patients were separated in two groups, i.e. an insulin-resistant group with a fasting G/I ratio of < 4.5(mg/10(-4) U) and an insulin-sensitive group with a fasting G/I ratio of >/=4.5(mg/10(-4) U). RESULTS: In our study, 58.06% of women with PCOS and BMI >or=25 (kg/m2) were insulin-resistant. There was no significant difference between the two groups in age or BMI. Sex hormone binding globulin (SHBG) levels were significantly lower in the insulin-resistant group (17.83 +/- 8.38 vs. 42.66 +/- 27.65 (nmol/l); p=0.0036) and they had a higher free testosterone index (19.38 +/- 8.91 vs. 9.55 +/-3.51(%); p=0.001) in comparison with the insulin-sensitive group. Progesterone levels were significantly lower in the IR group (2.41 +/- 2.50 vs. 7.05 +/- 8.04 (ng/ml); p=0.034). CONCLUSION: A fasting glucose to insulin ratio is a simple and useful test for identifying insulin-resistant obese women with PCOS. SHBG and progesterone (oligo-ovulation/anovulation) can be useful markers for long-term health risks in women with PCOS (diabetes mellitus type 2 and cardiovascular diseases). In this way we could identify the group of PCOS subjects and its subgroups, which would benefit from therapy with insulin sensitizers, with respect to the reduction of risks of chronic complications.

Adolescent↗
PubMed1990

Polycystic ovary syndrome.

Polycystic ovary syndrome is a disorder of unknown cause characterized by anovulation, hyperandrogenism, and gonadotropin secretory abnormalities producing oligo-ovulation or anovulation. Hyperinsulinemia and insulin resistance are important features of this syndrome. Because other causes of androgen excess may produce similar clinical and biochemical findings, PCO remains a diagnosis of exclusion. Treatment is directed toward relieving symptoms of hyperandrogenemia in order to stimulate ovulation, correcting obesity, and inducing regular menses to reduce the risk of endometrial cancer.

Female↗
PubMedDate not supplied

[Levels of estradiol, progesterone and testosterone in hyperprolactinemia].

In 69 patients with hyperprolactinemia the concentrations of FSH (foliculostimulating) hormone, LH (luteinization) hormone, PRL (prolactin), PRG (progesterone), T (testosterone) and E2 (estradiol) were determined by the RIA method on the 7th, 14th, and 21st day following the beginning of spontaneous or induced uterine bleeding. According to the recorded E2 and PRG concentrations, all the patients were divided into three groups: one group with the E2 and PRG concentrations within normal ovulation cycle values (N = 31); the second group with the E2 concentrations within normal values and the PRG values characteristic of the 21st day (N = 18), and the third group with the E2 concentrations below the lower normal values on the 7th and the 14th day and the PRG anovulation concentrations on the 21st day (N = 20). The mean values of the E2 concentrations in the hyperprolactinemic patients were significantly lower in all the three control groups (P less than 0.01; 0.05; 0.01) on the 7th day and (P less than 0.01; 0.05; 0.001) on the 14th day, which suggests the impairment of the follicular phase of the cycle. In the second and third groups there was no significant difference between the E2 concentrations on the 7th and the 14th day, while the PRG concentrations on the 21st day remained on the level of the anovulation values. Unlike the control group, the patients with hyperprolactinemia showed no significant increase of the Lh concentration on the 14th day. The effect of hyperprolactinemia on the impairment of the ovarian function is discussed.

Adult↗
PubMedDate not supplied

Serum levels of gonadotropins, prolactin, and progesterone in infertile female Africans.

To determine the prevalence of hormonal abnormalities in infertile African women, serum levels of luteinizing hormone, follicle stimulating hormone, prolactin, and progesterone were estimated using radioimmunoassay techniques during the midluteal phase in 2,047 female partners of infertile relationships. Of the patients investigated, 1,085 (53%) had abnormal serum levels of one or more of the hormones studied. Hyperprolactinemia, found in 537 (26.2%) of the patients, was the commonest hormonal abnormality. Serum progesterone level of 3 ng/mL or below which is indicative of anovulation was found in 235 (11.5%) patients, while the value of 5 ng/mL or below, suggestive of inadequate luteal functions, was found in another 121 (5.9%) patients. Since hyperprolactinemia, anovulation, and defective luteal function are treatable endocrine disorders, routine endocrine evaluation of infertile females in African societies is suggested.

Adolescent↗
PubMed1988

Dysfunctional uterine bleeding.

Dysfunctional uterine bleeding is classified by the character of the menstrual cycle: ovulatory or anovulatory. Anovulation can occur at any age and is physiologic in the first year or two after menarche and for several years before menopause. Anovulatory cycles are characteristically irregular and marked by prolonged episodes of bleeding unassociated with signs or symptoms of ovulation. Specific causes of anovulation such as hyperprolactinemia, thyroid disease, androgen excess, anorexia, obesity, and excess exercise can be treated specifically; otherwise, therapy depends upon patient goals. Cycle regulation can be affected by monthly courses of progestin, such as medroxyprogesterone acetate (Provera), 10 mg daily for 10 days each month. Contraception and cycle regulation can both be accomplished with oral contraceptives. Fertility, on the other hand, will require ovulation induction. Ovulatory dysfunctional uterine bleeding most prevalent in parous women between the ages of 20 and 40 is associated with regular cycle intervals and premenstrual molimina. Midcycle and perimenstrual spotting can often be treated with observation only, but depending upon patient and/or physician concerns, periodic hormonal suppression is effective. The management of menorrhagia should include the following: (1) exclusion of pathology in the genital tract; (2) reduction in activity during days of heavy flow; (3) the avoidance of aspirin in the week before and on days of flow; (4) nonsteroidal anti-inflammatory drugs; (5) cycle suppression--oral contraceptives, danazol (Danocrine), depo-progestin; (6) luteal phase progestin; and (7) surgical intervention.

Adult↗
PubMed1985

[Does prolactin have a role in the physiopathology of luteal insufficiency?].

A TRH-test was performed in 305 normoprolactinemic patients with gynecological disorders in order to appreciate the possible relationship between luteal defect, anovulation, galactorrhea and prolactin. The basal prolactin mean values of each group (normal cycle, pure luteal defect, luteal defect with persistent estrogenic influence, anovulation: with or without galactorrhea) were not different. However, some patients with luteal defect with persistent estrogenic influence and galactorrhea had an exaggerated response to TRH, and women with oligomenorrhea or amenorrhea had a low one. Unapparent hyperprolactinemia appears infrequent in normoprolactinemic patients.

Female↗
PubMed1985

Polycystic ovarian disease.

Polycystic ovarian disease represents a poorly defined spectrum of clinical disorders having oligo-ovulation or anovulation as a common feature. There is no single, universally accepted biochemical or clinical definition. Clinical findings usually include anovulation resulting in irregular uterine bleeding and infertility, androgen excess resulting in hirsutism and acne, and obesity. The patho-physiology involves altered functions of the hypothalamus, pituitary, ovary and adrenal glands, resulting in failure of folliculogenesis to regularly proceed to ovulation. The cause of the initiating event in this disease process remains enigmatic. Therapy for the various abnormalities in polycystic ovarian disease is tailored to a patient's needs and may include preventing endometrial hyperplasia, controlling irregular uterine bleeding, controlling hirsutism and inducing ovulation.

Female↗
PubMed1981

Monitoring of ovulation induction with HMG-HCG therapy by plasma estrogen and progesterone.

Seventeen patients with anovulation or luteal deficiency were tested with HMG-HCG for 40 cycles. Follicular development was monitored daily by measurement of immunoreactive plasma estrogen. Ovulation was evaluated by determination of plasma progesterone. Ovulation was induced in 16 patients and 37 of 40 cycles (93%). Fourteen pregnancies occurred in 13 patients. Plasma estrogen measurements in ovulatory cycles at the time of HCG injection ranged from 315 to 1,482 pg/ml (mean 764 pg/ml). Mild hyperstimulation occurred in two cycles with preovulatory estrogen values of 720 pg/ml and 784 pg/ml. The highest preovulatory estrogen level which was followed by anovulation was 493 pg/ml. The preovulatory estrogen peak in one triplet pregnancy measured 1,356 pg/ml. Determinants of treatment failure included inadequate follicular stimulation, interruption of HMG therapy for more than 1 day, previous ovarian wedge resection, and congenital anomaly of the uterus. Increase in body weight required higher doses of drug therapy in one case. We conclude that optimal estrogen levels prior to HCG injection range from 500 to 700 pg/ml. The risks for ovarian hyperstimulation and multiple pregnancy may be reduced and ovulation accomplished by daily administration of HMG until the defined estrogen level is reached.

Chorionic Gonadotropin↗
PubMed1984

Etiologic classification and sociomedical characteristics of infertility in 250 couples.

Two hundred fifty infertile couples were studied during a 30-month period. Of these, 77 couples (30.8%) were polygamous. Tubal disease was the commonest etiologic factor, being the sole factor in 24% and a factor in 41.2%. Oligo-azoospermia was the sole factor in 20.8% and a factor in 34.4%. Anovulation was the sole factor in 16.8%. Female factors were the sole findings in 129 patients (51.6%), while male factors were the sole findings in 54 (21.6%). In 36 (14.4%), combined factors were present. There were 56 (22.4%) pregnancies including 27 (63%) pregnancies in 43 patients who were treated for anovulation. There were five pregnancies in 103 patients with tubal disease. Thirty-five (62.5%) pregnancies ended in live births, while eight (14.3%) were abortions or ectopic gestations.

Adult↗
PubMed1981

[Hypophyseal response to LH-RH test, following use of non-aromatisable androgen on women with normal menstruation cycle (author's transl)].

Women with normal menstruation cycle were followed up for the hypophyseal response to LH-RH tests, following application of a non-aromatisable androgen. The purpose was to check up a hypothesis according to which hyperandrogenism was in no causative relationship with anovulation. The LH-RH test was applied twice to ten women with transsexualism who had an ovulatory menstruation cycle, one of them being used for control and the other immediately following four-day application of non-aromatisable androgen Ultandren (fluoxymesterone), Ciba, in the early follicular maturation phase of the menstruation cycle. The dose was 40 mg per diem, with the route of administration being oral. Hypophyseal reaction was assessed through the difference between the original value and the maximum of FSH and LH rise (radio-immunological measurement), 45 minutes following intravenous injection of 100 micrograms of LH-RH. Assessment was based on the phase-t test. The average differences between gonadotrophin values in the control cycle, on the one hand, and in the cycle under the impact of fluoxymesterone, on the other, were verified by simple t-test and pairs test. -- Non-aromatisable androgen fluoxymesterone did not depress with significance the depletion of either gonadotrophin in the women treated. Hypophyseal reaction to the LH-RH test was not substantially influenced by increased levels of non-aromatisable androgen. These results are likely to reinforce the doubts of the authors in the presence of an unambiguous direct causative relationship between hyperandrogenism and anovulation.

Adolescent↗
PubMed1982

[Direct effect of prolactin on the ovary by monolayer culture of human luteal cells].

In order to elucidate the mechanism of anovulation and luteal insufficiency that occur in hyperprolactinemia, the direct effect of prolactin (PRL) on luteal cells in vitro was investigated using human luteal cells in a monolayer cell culture. 1) The direct effect of PRL (that was kindly provided by the National Institute of Arthritis, Metabolism and Digestive Diseases) as seen in the production of P was such that when PRL concentrations were 1 through 100ng/ml the luteal stimulatory action was demonstrated, but in concentrations above 100ng/ml the stimulatory action was attenuated, and at 1 microgram/ml inhibitory effects were observed. 2) There was no significant difference between the PRL-added group and non-added group on the production of E2 and 17OHP. 3) Production of P in the HCG 100ng group increased to about 4 times that of the non-added group. Production of P in the group with simultaneous addition of PRL 1 microgram-HCG 100ng also showed a similar degree of increase. From the above, it is concluded that PRL alone exerts a direct effect on luteal cells that is luteotropic and luteolytic, depending on the different concentrations of PRL. These facts suggested that the direct inhibitory effect of PRL on the ovary was one of the causes of anovulation and luteal insufficiency during hyperprolactinemia in vivo.

Adult↗
PubMedDate not supplied

Abnormal production of androgens in women with breast cancer.

Two long and broad streams of medical literature, from the 1950's to date, have established the existence of two unrelated abnormalities of androgen production in women with breast cancer. One is the genetically determined presence of subnormal production of adrenal androgens (i.e. DHEA and DHEAS) in women with premenopausal breast cancer and their sisters, who are at increased risk for breast cancer. The other is excessive production of testosterone, of ovarian origin, in subsets of women with either premenopausal or postmenopausal breast cancer and women with atypical breast-duct hyperplasia, who are at increased risk for breast cancer; along with the hypertestosteronism, there is frequently chronic anovulation in the premenopausal patients. The combination of ovarian hypertestosteronism and chronic anovulation is characteristic of the polycystic ovary syndrome and is also frequently seen in women with abdominal ("android") obesity; both PCOS and abdominal obesity are known to be characterized by high risk for postmenopausal cancer. The elevated testosterone levels and the increased levels of insulin, IGF-I, and IGF-II that are seen in PCOS and abdominal obesity could favor the development of breast cancer in several ways, all of which have been demonstrated experimentally: binding of testosterone to cancer cells bearing testosterone receptors, with direct stimulation; intratissular aromatization of testosterone to estradiol, with stimulation of estrogen-sensitive cells; stimulation of the production of epithelial growth factor (EGF) by testosterone, with direct mitogenic effect of EGF on cancer cells; stimulation of aromatase by insulin and IGF-I; direct mitogenic stimulation of cancer cells by insulin, IGF-I, and IGF-II; and stimulation by IGF-I and IGF-II of the intratissular reduction of estrone to estradiol. Since PCOS is probably largely genetically determined, and abdominal obesity may also be, the hypertestosteronism of these conditions may represent a second genetically determined hormonal risk factor for breast cancer.

Adrenal Glands↗
PubMed1977

Clinical aspects of the polycystic ovary syndrome.

One hundred and one patients with polycystic ovary syndrome (PCO) were treated during an 11-year interval. Sixty-seven cases were classified as typical PCO with enlarged ovaries of probable ovarian origin (Type I) and 34 as atypical PCO of probable adrenal origin (Type II). Fifty-five patients were treated for anovulatory infertility with clomiphene citrate or other endocrine therapy as indicated. There was a 91% ovulatory response and 51% conception rate from therapy in cases of Type I PCO. In Type II PCO, adrenal suppressive therapy resulted in a 55% ovulatory response. Our data support the concept that anovulation of ovarian origin as seen in PCO Type I responds to clomiphene therapy, while anovulation secondary to adrenal hyperandrogenization should be treated by adrenal suppressive therapy.

17-Ketosteroids↗
PubMed1995

The effects of buserelin microparticles on ovarian function in healthy women.

OBJECTIVE: To investigate the tolerance, pharmacokinetics and pharmacodynamics of the microparticle formulation of buserelin, when it was administered subcutaneously. DESIGN: A single-blind, randomised, parallel-group design was used to investigate the duration of suppression of ovarian function associated with doses of 1.8 3.6 and 7.2 mg buserelin administered subcutaneously as microparticles. SETTING: The study was carried out at the Hoechst Research Centre for Clinical Pharmacology, Department of Pharmacology, University of the Orange Free State, Bloemfontein. PATIENTS: Thirty-two health premenopausal female volunteers aged between 19 and 39 years and weighing between 52 and 85 kg completed the study. OUTCOME MEASURES: Serum progesterone and oestradiol concentrations were measured twice weekly until normal ovarian function resumed, i.e. when serum progesterone concentrations increased to at least 8 nmol/l (a sign of ovulation) and oestradiol concentrations increased to values above 300 pmol/l. Serum and urinary concentrations of buserelin were measured at the same times as those of progesterone and oestradiol. RESULTS: Doses of 1.8 3.6 and 7.2 mg elicited anovulation for mean periods of 52, 77 and 113 days and suppressed ovarian production of oestrogen for 19, 38 and 69 days. Resumption of normal ovarian function occurred when serum buserelin concentrations decreased to between 0.03 and 0.05 microgram/ml. The correlation coefficient between dose and duration of anovulation was 0.75; the correlation coefficient between dose and duration of suppression of oestrogen production was 0.76. CONCLUSION: Apart from minor side-effects such as hot flushes, vaginal spotting and acne, the compound was tolerated well. We conclude that a good relationship exists between dose and duration of suppression of ovarian function. Doses of 3.6 - 7.2 mg buserelin should suppress oestrogen production for approximately 6 - 9 weeks and ovulation for 11 - 16 weeks.

Adolescent↗
PubMedDate not supplied

Fasting and postprandial serum insulin in Mexican adolescents with menstrual disorders.

PURPOSE: To investigate insulin serum concentrations in basal and stimulated conditions in a group of Mexican adolescents presenting menstrual disturbances. METHODS: A total of 77 post-menarchial adolescents were studied: 65 with a chronological age of 15 +/- 1.7 years (mean +/- SD) had persistent anovulation and represented the study group; 12 were normal ovulatory adolescents (15 +/- 1.2 years) and served as controls. Body mass index (BMI), waist to hip ratio (W/H), presence and severity of acne, hirsutism, acanthosis nigricans (AN) and follicular hyperkeratosis were recorded. Transabdominal pelvic ultrasound was performed and LH, FSH, estradiol, prolactin, testosterone, androstenedione and sex hormone binding globulin (SHBG) concentrations were measured in plasma by specific immunoassays. Glucose and insulin levels were determined in venous blood following an overnight fasting and two hours after a standardized breakfast. RESULTS: Anovulatory patients were divided in three groups depending on the presence of AN and overweight (BMI > 25). The insulin concentration in the study patients were remarkably higher than the values reported in the medical literature. Statistically significant differences were also found in fasting and postprandial insulin concentrations among the three anovulatory groups. Insulin values correlated with the severity of AN, W/H ratio, BMI and SHBG serum levels. CONCLUSIONS: Our study indicates that moderate to severe hyperinsulinemia is present in a high proportion of our adolescent anovulatory population. Whether hyperinsulinemia represents a transitory peripubertal event or is a predictive marker of chronic anovulation and metabolic derangement in adult life needs further investigation.

Adolescent↗
PubMed1997

[The value of plasma prolactin level determination in the diagnosis of postmenopausal osteoporosis].

Anovulation condition (estrogen deficiency due to high prolactin level) is linked with premature loss of bone mass. Bone mineral density was measured in the femur neck and the lumbar spine (L2-L4) with DEXA and the bone density was given by Z-score, which makes comparison to adult women's bone mass (normal reference). The examinations were carried out in two different groups. Bone mineral density was measured in the first group in 14 cases with hyperprolactinemic anovulation (aged 28 to 36 years). The average value of Z-score was -1.148 +/- 0.68. In the second group 39 patients (51.9 +/- 2.3 years) took part in the investigation within one year after menopause and the measured Z-score was less than -1.0 (-1.98 +/- 0.4). In the control group there were 40 postmenopausal patients (52.2 +/- 2.4 years) and their Z-score was more than -1.0 (-0.21 +/- 0.14). Prolactin value was 416 +/- 98 mU/l in the investigated group, while in the control group it was 238 +/- 76 mU/l (p < or = 0.05). Our results suggest that continuation of the antiprolactinemic (bromocryptine) treatment following completion of child-bearing appears to be indicated in premenopausal women with increased levels of serum prolactin. During the perimenopause endangered group, whose risk is increasing for postmenopausal osteoporosis, can be stated by determining prolactin level.

Adult↗