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Polycystic ovary syndrome is a diagnosis made in 5%-10% of women between late adolescence and the menopause. Patients may present with oligomenorrhoea or amenorrhoea, anovulation or infertility, hirsutism or acne. Women with the syndrome have at least seven times the risk of myocardial infarction and ischaemic heart disease of other women, and by the age of 40 years up to 40% will have type 2 diabetes or impaired glucose tolerance. Polycystic ovary syndrome is associated with insulin resistance, with consequent hyperinsulinaemia and (frequently) hyperlipidaemia and obesity. Recent research has shown that the application of diabetes management techniques aimed at reducing insulin resistance and hyperinsulinaemia (such as weight reduction and the administration of oral hypoglycaemic agents) can not only reverse testosterone and luteinising hormone abnormalities and infertility, but can also improve glucose, insulin and lipid profiles. The management of polycystic ovary syndrome should now include patient education and attention to diabetes and cardiovascular risk factors such as hyperlipidaemia, obesity, physical exercise, glucose intolerance, hypertension and cigarette smoking.
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PMID:Polycystic ovary syndrome: a new direction in treatment. 986 12

Polycystic ovary syndrome (PCOS) is classically characterised by ovarian dysfunction (oligomenorrhoea, anovulation and infertility), androgen excess (hirsutism and acne), obesity, and morphological abnormalities of the ovaries (cystic enlargement and stromal expansion). More recently, insulin resistance has been found to be common in PCOS, along with an increased prevalence of other features of the "metabolic syndrome", namely glucose intolerance, type 2 diabetes mellitus, and hyperlipidaemia. Hyperinsulinaemia is likely to contribute to the disordered ovarian function and androgen excess of PCOS. Reducing insulin resistance by lifestyle modifications such as diet and exercise improves endocrine and menstrual function in PCOS. These lifestyle modifications are the best initial means of improving insulin resistance. Metformin, an oral hypoglycaemic agent that increases insulin sensitivity, has been shown to reduce serum concentrations of insulin and androgens, to reduce hirsutism, and to improve ovulation rates. The effect of metformin alone on fertility rates is unknown. Some studies suggest that metformin will reduce total body weight to a small extent, but with a predominant effect on visceral adipose reduction. The effects of metformin on lipid abnormalities, hypertension or premature vascular disease are unknown, but the relative safety, moderate cost, and efficacy in reducing insulin resistance suggest that metformin may prove to be of benefit in combating these components of the "metabolic" syndrome in PCOS. Further properly planned randomised controlled trials are required.
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PMID:Metformin and intervention in polycystic ovary syndrome. Endocrine Society of Australia, the Australian Diabetes Society and the Australian Paediatric Endocrine Group. 1145 23

Isotretinoin is a vitamin-A derivative most commonly utilized in the treatment of severe recalcitrant nodulocystic acne. Derangement of lipid metabolism leading to increased triglyceride and cholesterol level has been reported after taking this drug. We report the case of a 43-year-old female with no identifiable risk factor for pancreatitis who developed acute pancreatitis associated with hyperlipidemia while being treated with isotretinoin for hidradenitis suppurativa. To our knowledge, this is the third reported case of isotretinoin-induced hyperlipidemia leading to acute pancreatitis.
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PMID:Acute pancreatitis secondary to isotretinoin-induced hyperlipidemia. 1184 76

The choice of currently available oral contraceptives (OCs) includes combined formulations in varying dosages and monophaic, biphasic, or triphasic form, sequential pills, synthetic progestin-only pills in macro or microdose, and injectable synthetic progestins. Before the advent of microdose pills, products were characterized by progestin or estrogen dominance. Rumors that microdose pills do not completely inhibit ovulation have hindered their acceptance in France, but research has shown that they inhibit ovarian secretions as effectively as more strongly dosed products. Their les profound inhibition of the hypothalamo-pituitary axis raises hopes of a lessened incidence of postpill amenorrhea. Progestin-only microdose pills allow considerable ovarian estrogen secretion, creating a veritable iatrogenic luteal insufficiency. Following the suppression of mestranol, the only estrogen used in OCs is ethinyl estradiol (EE). The only 19-norsteroid progestins which are fixed directly to the progesterone receptors are norethindrone and norgestrel; others such as lynestrenol, ethynodiol diacetate and norethindrone acetate are prohormones. Menstrual problems are among the most frequent side effects of minidose combined pills, but their incidence had dimished with the appearance of biphasic pills and the triphasic pills should offer even greater improvements. The frequency of thromboembolic venous accidents is firectly correlated to the estrogen dose of OCs, but arterial accidents and possibly arterial hypertension appear to be linked to the progestin dose. Synthetic progestins appear to diminish the high density lipoprotein (HDL) fraction of cholesterol and disturb glucose tolerance, while synthetic estrogens augment the HDL fraction of cholesterol and the very low density lipoprotein (VLDL) fraction of triglycerides, modify some coagulation factors, and elevate the plasma level of angiotensinogene. Dose levels and chemical structures of the constituents influence the metabolic effects of pill formulations. In current practice, minidose products are preferred because they cause fewer metabolic changes and are less likely to entail vascular risks. Sequential pills are prescribed for 1 cycle following induced abortion but are not used for long periods because they are not 100% effective, they carry a risk of endometrial hyperplasia, and they appear to increase risks of venous thromboembolism. A combination of 50 mcg EE and 2 mg cyproterone acetate may be prescribed for acne, and minidose combination pills may be used in case of fibroma or endometriosis. In case of contraindications to estrogen, a microdose or injectable progestin can be prescribed if their shortcomings are kept in mind. The current popularity of macrodose progestin-only pills in France has more to do with fashion than with science. All hormonal contraception should be avoided for women at risk, including smokers and those with hyperlipidemia or a family history of vascular accidents.
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PMID:[How to choose an oral contraceptive in 1984]. 1226 9

513 adolescent females attending a family planning center administered by the French Movement for Family Planning in Strasburg completed anonymous questionnaires between December 1984-June 1985 to identify the sociological and clinical characteristics of the clinic users. About 80% were 16-19 years old. 314 came unaccompanied to the center, 149 came with a friend, and 25 came with their partner. It was the 1st consultation for 278 respondents. 126 had been coming for less than 1 year, 67 for 1-2 years, 31 for 2-3 years, and 11 for more than 3 years. 83% were students. 312 resided in Strasburg or its suburbs and 201 resided elsewhere. Anonymity was the principal reason why clients travelled long distances to attend the center. 372 knew of the center through friends or sisters, 44 through the media, 40 through school, 11 through parents, and 7 through a doctor. 121 reported that their parents knew they used contraception and 382 that they did not know. 318 preferred a woman doctor for a contraceptive consultation, 180 did not care, and 6 preferred a man. Over half had their 1st menstrual period between the ages of 12 and 13. 172 were virgins at the time of their 1st consultation. The age of 1st intercourse was 14-17 years old for 81% and 15 or 16 for 48%. 155 used no contraception before visiting the center, 114 used withdrawal, 73 used condoms, 20 used spermicides, 38 used oral contraceptives (OCs) prescribed elsewhere, and 9 used other methods. 66% of prescriptions were for standard dosed pills because less than 2 years had passed since menarche, the cycles were irregular, or the client had acne or feared forgetting a pill. At the 3-month follow-up the prescription was changed to a lowdose pill in 43 cases because of side effects, while a low dose pill was changed to standard dose in 20 cases because of acne or forgetting. 24 girls came for a morning after pill and 31 for a pregnancy test. 9 reported they had already had abortions. 163 did not smoke, 152 smoked less than 1/2 pack daily, 150 smoked 1/2-1 pack, and 43 smoked more than 1 pack. 434 had a normal weight for their height and 56 were obese. 33% did not return after their 1st consulatation. Frank hyperlipidemia was rare among the clients tested.
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PMID:[Contraception in young girls. A survey conducted in the MFPF Family Planning Center, Strasbourg in 1985]. 1226 91

Isotretinoin is well recognised to cause hyperlipidaemia. This is most obvious during the second month of a 4-month course. Since there are no long-term data on lipid profiles, we have identified 30 subjects who have received 3 or more courses of isotretinoin. They had been exposed to a median of 24.5 months (range 12-103) isotretinoin therapy with a median total cumulative dose of 350 mg/kg (range 152-1221). The median serum cholesterol pre-treatment was 4.6 mmol/L (range 3-6.4). This compared to a median of 4.5 mmol/L (range 3-6.4) just prior to starting the final course. The median triglyceride levels before treatment and pre-final course were 0.8 mmol/L (range 0.3-1.7) and 0.92 mmol/L (range 0.4-2.6) respectively, indicating no significant change in cholesterol or triglyceride concentrations when measured prior to the first and last courses. In addition there was no correlation between cholesterol or triglyceride concentration before the final course of isotretinoin and the total cumulative dose of isotretinoin. We conclude that there appears to be little risk of causing hyperlipidaemia by prolonged therapy with isotretinoin in patients with acne.
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PMID:Retrospective survey of serum lipids in patients receiving more than three courses of isotretinoin. 1466 Feb 66

PCOS is a metabolic syndrome that exists throughout the world with much clinical heterogeneity. PCOS is now appreciated as encompassing two interrelated metabolic phenomena--insulin resistance and hyperandrogenism. Patients present with oligo-amenorrhea and clinical hyperandrogenism, and the diagnosis is based on clinical grounds with few laboratory tests necessary. Because patients are at higher than normal risk for diabetes, glucose intolerance, and hyperlipidemia, and perhaps at higher risk for coronary heart disease, newly diagnosed patients with PCOS should be evaluated for glucose intolerance and hyperlipidemia. The cornerstone of therapy today includes weight management, and further therapeutic intervention is focused on reproductive and cardiovascular health and treatment of insulin resistance. Clinical case continued The 17-year-old mentioned in the beginning of this article probably does have PCOS. She fits the clinical criteria: oligo-ovulation and hyper-androgenism (the acne and hirsutism). In addition, she is obese, which is also associated with PCOS. Her TSH and prolactin were normal, and as her presentation was not suggestive of an adrenal tumor or congenital adrenal hyperplasia (she had mild hirsutism, and those diagnoses are associated with more severe hyperandrogenism), no further laboratory evaluation was deemed necessary. Once the diagnosis was made, she was screened for lipid abnormalities and for glucose intolerance. Her LDL was 150, HDL 35; oral glucose tolerance test (OGTT) was normal. A pregnancy test was negative, and she was started on OCPs. Devoting herself to exercise and dietary change, she lost 10 pounds in her first 3 months after diagnosis. Her hirsutism and acne have improved with the OCPs and weight loss, and her menses are regular. She has elected to defer oral insulin sensitizers until her weight loss has stabilized. Findings PCOS is common in reproductive-aged women. Diagnosis is clinical and is supported by lab findings; there is significant clinical heterogeneity. Insulin resistance is likely central to the pathophysiology along with androgen excess. Health implications include infertility, diabetes, endometrial cancer, hyperlipidemia, and possibly coronary heart disease. Treatment is evolving and includes weight loss, OCPs, and insulin sensitizers.
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PMID:Polycystic ovary syndrome: a review for primary providers. 1502 92

Guggulsterone is the active ingredient in gugulipid, an organic extract of the Commiphora mukul plant. Gugulipid has been used for nearly 3000 years in Ayurvedic medicine, mainly as a treatment for arthritis. Herbal practitioners currently use gugulipid therapy in conditions as diverse as rheumatism, coronary artery disease, arthritis, hyperlipidemia, acne, and obesity. The active ingredient in gugulipid is guggulsterone, a plant sterol compound recently identified as a pregnane X receptor (PXR; NR1I2) ligand. We show herein that guggulsterone treatment represses the expression of cytochrome P450 2b10 (Cyp2b10) gene expression by inhibiting constitutive androstane receptor (CAR; NR1I3) activity in hepatocytes lacking functional PXR (PXR-knockout). We also show that PXR-CAR cross-talk determines the net activity of guggulsterone treatment toward Cyp2b10 gene expression. Using mammalian two-hybrid assays, we show that treatment with guggulsterone differentially affects protein cofactor recruitment to these two nuclear receptors. These data identify guggulsterone as an inverse agonist of the nuclear receptor CAR. When viewed together with the data showing that PXR and CAR expression is highly variable in different ethnic populations and that CAR expression is under the control of a circadian rhythm, our data provide important insight into the molecular mechanism of interindividual variability of drug metabolism. These data, together with the recent resolution of the crystal structures of PXR and CAR, will likely aid in the rational design of more specific CAR inverse agonists that are currently viewed as potential antiobesity drugs.
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PMID:The ratio of constitutive androstane receptor to pregnane X receptor determines the activity of guggulsterone against the Cyp2b10 promoter. 1583 98

Esterification of sterols, fatty acids and other alcohols into biologically inert forms conserves lipid resources for many cellular functions. Paradoxically, the accumulation of neutral lipids such as cholesteryl ester or triglyceride, is linked to several major disease pathologies. In a remarkable example of genetic expansion, there are at least eleven acyltransferase reactions that lead to neutral lipid production. In this review, we speculate that the complexity and apparent redundancy of neutral lipid synthesis may actually hasten rather than impede the development of novel, isoform-specific, therapeutic interventions for acne, type 2 diabetes, obesity, hyperlipidemia, fatty liver disease, and atherosclerosis.
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PMID:Regulation of triglyceride metabolism. I. Eukaryotic neutral lipid synthesis: "Many ways to skin ACAT or a DGAT". 1709 52

Steroid cell tumors, not otherwise specified, are rare ovarian sex cord-stromal tumors with malignant potential. The majority of these tumors produce steroids, with testosterone being the most common. A 44-year-old woman with hypothyroidism and hyperlipidemia presented with abrupt onset of oligomenorrhea, progressive virilization as acne, hirsutism and clitoromegaly, and a non-palpable pelvic mass. The preoperatively elevated serum testosterone level returned to normal after salpingo-oophorectomy, and then menstrual flow became regular.
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PMID:Hypothyroidism and hyperlipidemia with a virilizing ovarian steroid cell tumor, not otherwise specified. 1745 54


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