Polycystic Ovarian Syndrome & PCO-like Syndrome


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The Book	Polycystic Ovarian Syndrome & PCO-like Syndrome by Joseph Collins, Rn,ND
Menopause Type^® Questionnaire	Managing Androgen Excess Disorders in Women
Menopause Type^® Questionnaire	While obesity and infertility are the dysfunctions typically focused on in women with PCOS, recognizing the additional dysfunctions, and addressing the underlying metabolic imbalances, is the key to restoring optimal health and quality of life, and correcting the complex pathophysiology of androgen excess. These women are at great risk for insulin resistance, diabetes, dyslipidemia, cancers and cardiovascular disease. ⁽¹⁾ In addition, many suffer with increased discomforts due to a predisposition towards inflammation, and with psychiatric distress due to a higher risk for aggressive and depressive mood disorders.			Acne Aggression Alopecia Cancer Risk Hirsutism Hyperlipidemia Hypertension Hypoprogestinemia Hypothyroidism Inflammation Insulin Resistance Oxidative Stress Preeclampsia
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	In premenopausal women, polycystic ovarian syndrome (PCOS), which affects 5% to 7% of women of reproductive age, often presents with additional problems such dysfunctional uterine bleeding and infertility due to the anovulation commonly observed in PCOS.



	To make matters more complicated, there is a more nascent form of PCOS described as PCO-like syndrome that has been observed at a relatively young age in girls undergoing precocious adrenarche. ⁽²⁾


	Androgen excess may additionally affect women of child bearing age by precipitating and increased risk of preeclampsia. In addition, the significant increase in androgen concentrations during pregnancy in PCOS women could provide a potential source of androgen excess for the fetus. ⁽³⁾ In addition to infertility and obesity, the variant presentation of androgen excess in women typically present with twelve additional dysfunctions, which are caused by the collective actions of six metabolic imbalances.






	Twelve Additional Dysfunctions Associated with Androgen Excess in Women.
	Acne: Acne, with inflammation of the pilo-sebaceous follicle may be one of the symptoms of androgen excess in women which may be observed from puberty through menopause. ^(4,5,6)

	Aggression: Significant positive correlations were seen between serum testosterone concentrations and the tests scores for verbal aggression and anger.⁽⁷⁾Elevated testosterone levels are significantly related to moods such as anger and tension.⁽⁸⁾ Even a single dosage of testosterone (0.5 mg) induced an inclination toward aggression in healthy young women.⁽⁹⁾ Testosterone concentrations also correlated with anger prepartum & postpartum.⁽¹⁰⁾



	Alopecia: Androgenic alopecia in women may be related to both androgen excess and higher levels of 5-alpha reductase and androgen receptors in some hair follicles.^{(11, 12)} Sustained microscopic follicular inflammation with connective tissue remodeling, eventually resulting in permanent hair loss, is considered a possible cofactor in androgen alopecia. ⁽¹³⁾



	Cancer Risk: There are increased endometrial cancer risks among pre- and postmenopausal women who have elevated plasma androstenedione and testosterone. Chronic hyperinsulinemia, common in women with androgen excess, is also a risk factor for endometrial cancer. ^(14,15)


	Hirsutism: Over 50% of women with even minimal unwanted hair growth may have androgen excessive disorders and should have an evaluation of their hormones. ⁽¹⁶⁾

	Hyperlipidemia: Women with androgen excess are at a higher than normal risk for hyperlipidemia especially when accompanied by obesity.^(17,18) Women with PCOS typically have increased triglyceride levels, decreased total HDL and HDL2 levels, and increased total cholesterol and fasting LDL levels.⁽¹⁹⁾


	Hypoprogestinemia: The frequent observation of low progesterone levels in studies of PCOS indicate that there is a frequent need to support the ability of the body to make endogenous progesterone.^{(20, 21, 22, 23)}

	Hypertension: Androgen excess in women results in increased risk for hypertension & heart disease.⁽²⁴⁾

	Hypothyroidism: Hypothyroidism has often been associated with PCOS, though it does not occur in all cases. Hypothyroidism (often autoimmune hypothyroidism) can either initiate, or maintain or worsen the syndrome. Correction of hypothyroidism, if present, would therefore form an important aspect in the management of PCOS.^{(25, 26)}



	Inflammation: Some women with androgen excess have a genetic predisposition towards elevated inflammation, which may further exacerbate the metabolic processes leading to the androgen excess disorder. ⁽²⁷⁾


	Insulin Resistance: Insulin resistance is also a common finding in women with androgen excess, as is the compensatory hyperinsulinemia, and increased risk of type 2 diabetes mellitus. ^(28,29)

	Oxidative Stress: There is both an increase in oxidative stress and a decrease in antioxidant status in androgen excess women with PCOS. This increased oxidative stress and decreased antioxidant capacity is related to central obesity, age, blood pressure, serum glucose, insulin and triglyceride levels and insulin resistance. This increased oxidative stress may contribute to the increased risk of cardiovascular disease in women with PCOS. ^{(30, 31, 32)}


	Preeclampsia: An association has been noted between preeclampsia and androgen excess. A history of preeclampsia appears to be associated with elevated levels of testosterone based on a study comparing twenty-two women with prior preeclampsia and 22 control women matched by age and body mass index.⁽³³⁾



	Controlling Androgen Excess Disorders
	In addition to weight management, measures aimed at controlling the dangers of androgen excess in women include various pharmacological agents such as oral contraceptives⁽³⁴⁾, peripheral androgen blockade (spironolactone, flutamide, cyproterone acetate, or finasteride)^(35,36), insulin-sensitizing agents (metformin, rosiglitazone).^(37,38) and antiandrogen (bicalutamide for treatment of hirsutism) ⁽³⁹⁾.


	Approaching androgen excess through diet, lifestyle, and natural therapies include addressing the six specific metabolic imbalances often seen in woman with PCOS and PCO-like syndrome. Many of these imbalances are also evidenced in androgen excess Menopause Types_®, seen in perimenopause, menopause & postmenopause women.


	1.	Decrease oxidative stress with antioxidant rich multi-vitamin/mineral formulation.
	2.	Decrease inflammation and improve cell membrane response to hormones with an essential fatty formulation that has a high DHA:EPA ratio.
	2.
	3.	Decrease androgen function and affects of androgens with a phytotherapeutic anti-androgen formulation that also addresses inflammation, insulin resistance and other effects of androgen excess.


	4.	Increase progesterone production and function with a phytotherapeutic formulation that improves the function of progesterone producing tissue, and the function of tissues that respond to progesterone.
	4.
	5.	Improve the function of insulin producing cells in the pancreas, and the function of cells that respond to insulin, so as to decrease the insulin resistance, by using a phytotherapeutic formulation to improve insulin and glucose function.
	5.
	6.	Improve the function of thyroid producing cells within the thyroid, and the function of cells throughout the body which respond to thyroid, by using a phytotherapeutic formulation to improve thyroid function.
	6.
	By addressing oxidative stress, inflammation and membrane health at the cellular level, androgen excess, and the production and function of progesterone, insulin and thyroid hormones, we are able to restore optimal function, and improve quality of life in women with androgen excess disorders.



References :*(1) Derman RJ. Androgen excess in women. Int J Fertil Menopausal Stud. 1996 Mar-Apr;41(2):172-6. Review.(2) Lazar L, Kauli R, Bruchis C, Nordenberg J, Galatzer A, Pertzelan A. Early polycystic ovary-like syndrome in girls with central precocious puberty and exaggerated adrenal response. Eur J Endocrinol. 1995 Oct;133(4):403-6.(3) Sir-Petermann T, Maliqueo M, Angel B, Lara HE, Perez-Bravo F, Recabarren SE. Maternal serum androgens in pregnant women with polycystic ovarian syndrome: possible implications in prenatal androgenization. Hum Reprod. 2002 Oct;17(10):2573-9.(4) Buccola JM, Reynolds EE. Polycystic ovary syndrome: a review for primary providers. Prim Care. 2003 Dec;30(4):697-710. Review.(5) Azziz R, Sanchez LA, Knochenhauer ES, Moran C, Lazenby J, Stephens KC, Taylor K, Boots LR. Androgen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab. 2004 Feb;89(2):453-62.(6) Vexiau P, Chivot M. [Feminine acne: dermatologic disease or endocrine disease?] Gynecol Obstet Fertil. 2002 Jan;30(1):11-21. Review. French.(7) Prochazka H, Anderberg UM, Oreland L, Knorring LV, Agren H. Self-rated aggression related to serum testosterone and platelet MAO activity in female patients with the fibromyalgia syndrome. World J Biol Psychiatry. 2003 Jan;4(1):35-41.(8) van Honk J, Tuiten A, Verbaten R, van den Hout M, Koppeschaar H, Thijssen J, de Haan E. Correlations among salivary testosterone, mood, and selective attention to threat in humans. Horm Behav. 1999 Aug;36(1):17-24.(9) van Honk J, Tuiten A, Hermans E, Putman P, Koppeschaar H, Thijssen J, Verbaten R, van Doornen L. A single administration of testosterone induces cardiac accelerative responses to angry faces in healthy young women. Behav Neurosci. 2001 Feb;115(1):238-42.(10) Hohlagschwandtner M, Husslein P, Klier C, Ulm B. Correlation between serum testosterone levels and peripartal mood states. Acta Obstet Gynecol Scand. 2001 Apr;80(4):326-30.(11) Rosenfield RL, Lucky AW. Acne, hirsutism, and alopecia in adolescent girls. Clinical expressions of androgen excess. Endocrinol Metab Clin North Am. 1993 Sep;22(3):507-32. Review.(12) Price VH. Androgenetic alopecia in women. J Investig Dermatol Symp Proc. 2003 Jun;8(1):24-7. Review.(13) Trueb RM. Molecular mechanisms of androgenetic alopecia. Exp Gerontol. 2002 Aug-Sep;37(8-9):981-90. Review.(14) Kaaks R, Lukanova A, Kurzer MS. Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1531-43. Review.(15) Heim SC, De Geyter C, Siegrist W, Bilz S, Keller U. [Polycystic ovary syndrome--only relevant in reproductive medicine?] Ther Umsch. 1999 May;56(5):271-5. Review. German.(16) Souter I, Sanchez LA, Perez M, Bartolucci AA, Azziz R.The prevalence of androgen excess among patients with minimal unwanted hair growth. Am J Obstet Gynecol. 2004 Dec;191(6):1914-20.(17) Buccola JM, Reynolds EE. Polycystic ovary syndrome: a review for primary providers. Prim Care. 2003 Dec;30(4):697-710. Review.(18) Maitra A, Meherji PK, Desai MP, Gokral JS, Donde UM, Joshi UM. Lipoprotein lipids in androgen excess--a study among Indian women. Int J Fertil Menopausal Stud. 1994 Jul-Aug;39(4):218-22.(19) Talbott E, Guzick D, Clerici A, Berga S, Detre K, Weimer K, Kuller L. Coronary heart disease risk factors in women with polycystic ovary syndrome. Arterioscler Thromb Vasc Biol. 1995 Jul;15(7):821-6.(20) Meenakumari KJ, Agarwal S, Krishna A, Pandey LK. Effects of metformin treatment on luteal phase progesterone concentration in polycystic ovary syndrome. Braz J Med Biol Res. 2004 Nov;37(11):1637-44. Epub 2004 Oct 26. PMID: 15517078.(21) Orio F Jr, Palomba S, Cascella T, Tauchmanova L, Di Biase S, Labella D, Russo T, Pellicano M, Savastano S, Zullo F, Lombardi G, Colao A. Adrenal adenoma and normal androgen levels in a young woman with polycystic ovaries: a case of idiopathic hirsutism? J Endocrinol Invest. 2004 Jan;27(1):61-6. PMID: 15053246.(22) Janssen OE, Mehlmauer N, Hahn S, Offner AH, Gartner R. High prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome. Eur J Endocrinol. 2004 Mar;150(3):363-9. PMID: 15012623.(23) Hamori M, Urbancsek J, Szendei G, Nemet J. The role of ultrasonography in treating polycystic ovary syndrome.Acta Chir Hung. 1988;29(1):27-34. PMID: 3293336.(24) Heim SC, De Geyter C, Siegrist W, Bilz S, Keller U. [Polycystic ovary syndrome--only relevant in reproductive medicine?] Ther Umsch. 1999 May;56(5):271-5. Review. German.(25) Sridhar GR, Nagamani G. Hypothyroidism presenting with polycystic ovary syndrome. J Assoc Physicians India. 1993 Feb;41(2):88-90. PMID: 8053991. (26) Pallotti S, Gasbarrone A, Franzese IT. [Relationship between insulin secretion, and thyroid and ovary function in patients suffering from polycystic ovary] Minerva Endocrinol. 2005 Sep;30(3):193-7. Italian. PMID: 16208308.(27) Escobar-Morreale HF, Calvo RM, Villuendas G, Sancho J, San Millan JL. Association of polymorphisms in the interleukin 6 receptor complex with obesity and hyperandrogenism. Obes Res. 2003 Aug;11(8):987-96.(28) Zarate A, Moran C, Hernandez M, Saucedo R. [Current criterion for diagnosing polycystic ovary syndrome] Ginecol Obstet Mex. 2004 Jun;72:283-6. Review. Spanish.(29) Chang RJ. A practical approach to the diagnosis of polycystic ovary syndrome. Am J Obstet Gynecol. 2004 Sep;191(3):713-7. Review.(30) Sabuncu T, Vural H, Harma M, Harma M. Oxidative stress in polycystic ovary syndrome and its contribution to the risk of cardiovascular disease. Clin Biochem. 2001 Jul;34(5):407-13.(31) Duleba AJ, Foyouzi N, Karaca M, Pehlivan T, Kwintkiewicz J, Behrman HR. Proliferation of ovarian theca-interstitial cells is modulated by antioxidants and oxidative stress. Hum Reprod. 2004 Jul;19(7):1519-24. Epub 2004 Jun 03.(32) Fenkci V, Fenkci S, Yilmazer M, Serteser M. Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease. Fertil Steril. 2003 Jul;80(1):123-7(33) Laivuori H, Kaaja R, Rutanen EM, Viinikka L, Ylikorkala O. Evidence of high circulating testosterone in women with prior preeclampsia. J Clin Endocrinol Metab. 1998 Feb;83(2):344-7.(34) Guzick DS. Polycystic ovary syndrome. Obstet Gynecol. 2004 Jan;103(1):181-93.(35) Azziz R. The evaluation and management of hirsutism. Obstet Gynecol. 2003 May;101(5 Pt 1):995-1007. Review.(36) Ajossa S, Guerriero S, Paoletti AM, Orru M, Melis GB. The treatment of polycystic ovary syndrome. Minerva Ginecol. 2004 Feb;56(1):15-26.(37) Zheng Z, Li M, Lin Y, Ma Y. [Effect of rosiglitazone on insulin resistance and hyperandrogenism in polycystic ovary syndrome] Zhonghua Fu Chan Ke Za Zhi. 2002 May;37(5):271-3. Chinese.(38) Baillargeon JP, Jakubowicz DJ, Iuorno MJ, Jakubowicz S, Nestler JE. Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity. Fertil Steril. 2004 Oct;82(4):893-902.**(39) Muderris II, Bayram F, Ozcelik B, Guven M. New alternative treatment in hirsutism: bicalutamide 25 mg/day. Gynecol Endocrinol. 2002 Feb;16(1):63-6.

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