In the section on Endocrinology there have been 8 articles on PCO Polycystic Ovarian Disease, Polycystic Ovarian Syndrome and PCO Polycstic Ovaries.
The first article :
Prevalence of the Polycystic Ovary Syndrome in Unselected Black and White Women of the Southeastern United States: A Prospective Study.
ES Knochenhauer, et al (Univ of Birmingham, Ala) J Clin Endocrinol Metab 83:3078-3082,1 998.
Conclusions – In this population, the prevalence of hirsutism ranged from 2% to 8%, depending with an F-G score of 6 or more as the cutoff, 3.4% of black women and 4.7% of white women had PCOS as defined. Thus polycystic ovarian syndrome may be one of the most common reproductive endocrinologic disorders in women.
Editors comments: The prevalence of PCOs in an unselected population of women has previously been estimated using ovarian morphologic changes observed sonographically or directly at the time of a surgical procedure. However, with the use of these criteria the prevalence of polycystic ovaries (PCOs), not polycystic ovary syndrome (PCOS) is determined. In this study of unselected women, the investigators used the objective criteria of hirsuitism , elevated circulating androgen levels, or both , in combination with a history of oligomenorrhoea and the exclusion of other endocrinologic disorders to make the diagnosis of PCOS. With this clinical and endocrinologic definition of polycystic ovary syndrome the prevalence of the disorder was found to be 4% of an unselected group of 277 women. One third of the women with PCOS were overweight. These data indicate that PCOS is a relatively common endocrinologic disorder. Therefore, all individuals who provide health care to women need to learn how to diagnose and manage PCOS.
The second article:
The Prevalence of Polycystic Ovaries in Healthy Women.
R Koivunen, et al (Univ Hosp of Oulu, Findland; Helsinki City Maternity Hosp; Univ of Turku, Finland) Acta Obstet Gynecol Scand 78:137-141, 1999.
In healthy women, the prevalence of polycsytic ovaries varies with age. The findings are more common in women aged 35 years or young girls or than in those aged 36 years or older. It remains unclear if women with polycystic ovaries will later develop full-blown polycystic ovary syndrome; however, the hormonal parameters and clinical findings among women with polycystic ovaries mimicked those with polycystic ovary syndrome.
The results of this study of a group of women without the clinical manifestation of polycystic ovary syndrome (PCOS) found that 14% had ovaries with the sonographic appearance of polycystic ovaries (PCOs). Among women younger than 36 years, one fifth had ovaries that appeared polycystic when vaginal probe sonography was performed. None of this group of women had oligomenorrhea or infertility. Thus, clinicians need to differentiate women with PCOS from those with ovaries that have the sonographic appearance of PCO. As reported earlier, not all women with Polycystic Ovaries Syndrome have Polycystic Ovary and as shown in this study, not all women with Polycystic Ovary have Polycystic Ovary Syndrome.
The third article –
Transvaginal Ultrasound Appearances of the Ovary in Normal Women and Hirsute Women with Oligomenorrhoea.
Fox R (Univ of Bristol, England) Aust NZ J Obstet Gynaecol 39:63-68,1999.
Conclusion – In women with polycystic ovary disease, the classical ultrasound features are not consistently present, and the absence of increased follicularity at scan does not exclude a diagnosis of polycystic ovary. The diagnosis could be made with 15 or more small follicles per ovary. An expanded echogenic ovarian stroma was found in all the women with hirsuitism.
There are 2 articles on the impaired glucose tolerance and diabetes in women with polycystic ovary syndrome.
1) Prevalence of Impaired Glucose Tolerance and Diabetes in Women with Polycystic Ovary Syndrome.
DA Ehrmann, et al (Univ of Chicago). Diabetes Care 22: 141-146, 1999.
2) Prevalence and Predictors of Risk for Type 2 Diabetes Mellitus and Impaired Glucose Tolerance in Polycystic Ovary Syndrome: A Prospective, Controlled Study in 254 Affected Women.
RS Legro, et al (Pennsylvania State Univ, Hershey; Brigham and Women’s Hosp, Boston) J Clin Endocrinol Metab 84:165-169, 1999.
Both these articles are reviewed by Editor, D.R. Mishell Jr, with a comment that similar results were found in these 2 studies in which oral glucose tolerance tests (OGTTs) were performed in 2 large groups of women with clinical and endocrinologic changes indicating the presence of polycystic ovarian syndrome PCOS.
In the study by Ehrmann et al with 35% of 122 young women with PCOS had impaired glucose tolerance and 10% had non-insulin dependent diabetes mellitus (NIDDM). In the study of Lego et al 31% of 254 young women of similar age had impaired glucose tolerance and 7.5% had diabetes. In both groups, the incidence of glucose abnormalities was higher in obese than nonobese women. It would appear advisable to perform an OGTT at the time of diagnosis of PCOS and periodically thereafter. If abnormalities in glucose metabolism are found, appropriate interventions, such as diet and exercise, should be recommended to prevent or delay the conversion of IGT to NIDDM. Individuals with NIDDM should have appropriate therapy.
Mortality of Women with Polycystic Ovary Syndrome at Long-term Follow-up.
T Pierpoint, et al (London School of Hygiene and Tropical Medicine; Univ College London; Chelsea and Westminister Hosp, London). J Clin Epidemiol 51: 581-586, 1998.
Authors have studied mortality in large group of patients and came to the conclusion even though PCOS is associated with diabetes, lipid abnormalities, and other cardiovascular risk factors, women with PCOS do not have markedly higher than average mortality from circulatory disease.
Clinical Outcome After Unilateral Oophorectomy in Patients with Polycystic Ovary Syndrome.
E Kaaijk, et al (Academic Med Centre, Amsterdam) Hum Reprod. 14: 889-892, 1999.
In most of the women in this series, unilateral oophorectomy restored ovulatory function for many years. It does not appear to result in premature ovarian failure. Nevertheless, this treatment should not be the standard for CC-resistant women with PCOS.
Editorial comment: Many anovulatory women with PCOS fail to ovulate after treatment with ovulation-inducing agents, including CC, human menopausal gonadotropin, and follicle-stimulating hormone. Partial ovarian destruction with electrocautery or laser has been used to successfully induce ovulation in many women with PCOS who fail to ovulate in response to ovulation inducing agents.
Unilateral oophorectomy is no longer used as a means to induce ovulation in women with PCOS. However, as reported in this series, if other methods including electrocoagulation of the ovaries, fail to induce ovulation, one may consider performing unilateral oophorectomy.
R.L. Barbieri, Boston, Massachusetts
Induction of ovulation in infertile women with hyperandrogenism and insulin resistance.
Am J Obstet Gynecol, Dec.2000; 183: 1412-8
The polycystic ovary syndrome is a common cause of anovulatory infertility. Women with severe insulin resistance are a unique subset of polycystic ovary syndrome. The syndrome of hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN syndrome) is one presentation of the insulin-resistant subset of polycystic ovary syndrome. Insulin resistance and hyperandrogenism are caused by genetic and environmental factors. In women with anovulatory infertility caused by hyperandrogrenism and insulin resistance, clomiphene citrate treatment often fails to result in pregnancy. For these women, weight loss and insulin sensitizers can be effective methods of inducing ovulation and pregnancy and may reduce the number of clomiphene-resistant women with polycystic ovary syndrome who are treated with gonadotropins, ovarian surgery, or in vitro fertilization-embryo transfer.
Clinical findings that suggest insulin resistance and hyperinsulinaemia
Physical findings associated with insulin resistance
· Body mass index >27 kg/m2
· Waist-to-hip ratio >0.85
· Waist >100 cm
· Acanthosis nigricans
· Numerous achrochordons (skin tags).
How can clinicians detect insulin resistance and hyperinsulinemia?
Laboratory tests that have been proposed to be useful in detecting insulin resistance include fasting insulin concentration, fasting glucose to-insulin ratio, glucose or insulin response to an oral or intravenous glucose challenge, glucose response to an intravenous injection of insulin, and glucose-insulin clamp studies (e.g. euglycemic hyperinsulinemic clamp). A major problem is that the least resource-intensive laboratory techniques for diagnosing insulin resistance and hyperinsulinemia is almost always associated with insulin resistance, but many insulin-resistant women do not have fasting hyperinsulinemia.
Approved by Food and Drug Administration for Ovulation induction
Requires intensive cycle monitoring
Risk of ovarian hyperstimulation
Risk of high-order multiple gestation
Not approved by Food and Drug Administration for ovulation induction
Pregnancy category B drug
Does not require intensive cycle monitoring
Low risk of ovarian hyperstimulation
Low risk of high-order multiple gestation.
Contraindicated in women with renal dysfunction
Anna P. Ferraretti, Luca Gianaroli, Maria C Magli et al
Transvaginal ovarian drilling: a new surgical treatment for improving the clinical outcome of assisted reproductive technologies in patients with polycystic ovary syndrome.
Fert. &Ster.vol.76(4), Oct.2001, pg.812-6
Objective: To evaluate the efficacy of transvaginal ovarian drilling (TVOD) in patients with polycystic ovary syndrome (PCOS) who were undergoing IVF treatment.
Design : Pilot Study
Setting : Reproductive medicine unit
Patients : Eleven patients with PCOS undergoing treatment with assisted reproductive technology (ART).
Interventions: Selecti on criterion for TVOD was repeated poor performance in ³2 previous IVF cycles .
Main outcome measures: Controlled ovarian hyperstimulation parameters, number of eggs collected, fertilization rate, embryo cleavage rate, implantation rate, pregnancy rate compared with the cycles before TVOD.
Results: In the cycle after TVOD, a significantly higher dosage of FSH was used (33.5 ± 12 IU VS 5.22 ± 15 IU) to collect a higher number of oocytes in the presence of similar E2 values at the day of hCG administration. This resulted in significantly higher fertilization and cleavage rates (27% vs 66% and 54% vs 72%, respectively). The pregnancy and the implantation rates after TVOD were similar to those for normovulatory patients undergoing IVF for tubal factor infertility during the study period.
Conclusion: Data suggest that the TVOD is effective in improving IVF results in difficult to treat patients with PCOS, and it is less invasive and less expensive when compared with laparoscopic ovarian diathermy.
Ahmed Saleh, David Morris, et al
Effects of lapraoscopic ovarian drilling on adrenal steroids in polycystic ovary syndrome patients with and without hyperinsulinemia
Fert.& Ster. Vol.75(3), March 2001, pg.501-4
PCOS women with hyperinsulinemia respond differently to laparoscopic ovarian drilling than do those with normoinsulinemia. Among women with hyperinsulinemia, surgery decreases glucose and insulin responses to OGTT. Regardless of the insulin level, laparoscopic ovarian drilling does not influence adrenal steroid dynamcis.
The presence of obesity is associated with insulin resistance. Insulin increases lipoprotein lipase activity, promoting lipid accumulation. Hyperinsulinemia and insulin resistance contribute the elevated ovarian androgens and subsequently to anovulation. After ovarian drilling, the correlation between BMI and insulin levels is lost. This might be consistent with the observation that body weight does not influence the efficacy of laparoscopic ovarian drilling.
Laurel A Stadtmauer, Sameh K Toma, et al
Metformin treatment of patients with polycystic ovary syndrome undergoing in vitro fertilization improves outcomes and is associated with modulation of the insulin-like growth factors.
Fert.& Ster. Vol.75(3), March 2001, pg.505-9
Objective: To determine if metformin therapy improves in vitro fertilization (IVF) outcomes in patients with clomiphene-resistant polycystic ovarian syndrome (PCOS).
Design: Retrospective data analysis of selective group of patients.
Patients: Forty-six women with clomiphene citrate-resistant PCOS underwent 60 cycles of IVF embryo transfer with intracytoplasmic sperm injection.
Main Outcome measures: Total number of follicles; serum estradiol (E2) on the day of hCG administration and the cycle’s E2 maximum; total number of oocytes, mature oocytes, embryos, fertilization and pregnancy rates; and follicular fluid levels of insulin-like growth factors (IGF-I, IGF-II) and IGF-binding proteins (IGFBP-1, IGFBP-3).
Results: In patients treated with metformin, the total number of follicles on the day of hCG treatment was decreased (23 ± 1.2 vs 33 ± 2.6) with no change in follicles
³14mm in diameter (21 ± 1.2 vs 25 ± 1.7). Metformin treatment did not affect the mean number of oocytes retrieved (22 ± 2.9 vs 20.3 ± 1.5). However, the mean number of mature oocytes (18.4 ± 1.5 vs 13 ± 1.5) and embryos cleaved (12.5 ± 1.5 vs 5.9 ± 0.9) were increased after metformin treatment. Fertilization rates (64% vs 43%) and clinical pregnancy rates (70% vs 30%) were also increased. Metformin led to modulation of preovulatory of follicular fluid IGF levels with increases of IGF-I (140 ± 8 VS.109 ± 7 ng/mL) and decreased of IGFBP-1 (133 ± 8 vs 153 ± 9 ng/mL).
Conclusions: Metformin use appears to improve IVF outcomes in patients with clomiphene citrate resistant PCOS.
Discussion: This preliminary study supports the use of metformin in PCOS patients and shows a beneficial effect on the number of mature oocytes and the rates of fertilization, embryos cleaved, and pregnancy. Metformin was also associated with changes in ovarian stimulation. There appears to be a shift in follicle size, reducing the number of small cohort follicles. In addition there was a slower rise of E2 levels, lower peak E2 levels, and fewer days of “coasting.”