4. Androgens and PCO

About 10–12% of women in reproductive age suffer from androgen excess sign and symptom. It can be caused by androgen overproduction (from ovary or adrenal gland) or secondary to increased sensitivity of pilosebaceous unit (with normal level of androgens). Hyperandrogenemia is another hallmark of PCOs; mainly by ovarian resource and less by adrenal. In PCOs women, 60% of serum androstenedione and testosterone (T) are secreted by ovary. Surprising, ovarian androgens will not prominently affect LH production, thus an elevation in free testosterone or androstenedione will not decrease ovarian synthesis of these androgens in women, contrasting to men.

tumor necrosis factor-alpha (TNF-α), interleukins (IL-16 and -18), and plasminogen activator inhibitor in PCO patients accompany with abdominal obesity and more specific with visceral fat [46]. Low-grade inflammation situation by increased level of adiponectin, resistin, IL-6, and TNF-α in non-obese PCO women have been approved [47]. Also, it has been shown that inhibition of nutrient-induced inflammation decreases ovarian androgen secretion and induces ovulation in lean PCOs woman without clinical IR or abdominal adiposity. Therefore, inflammation directly encourages ovarian dysfunction in PCOs women distinctly from insulin resistance or excess adiposity [48]. There is evidence that non-steroidal anti-inflammatory agent administration in lean PCO women can reduce androgen secretion

Lean Women with Polycystic Ovary Syndrome http://dx.doi.org/10.5772/intechopen.70621 27

Dose inflammation have pathophysiologic role in this syndrome or may be its consequence remain still unclear. Inflammation as a chronic immune activation, prevents ovulation, increases androgen production by ovary and adrenal gland and disrupts hormonal receptors. Most of long-term complications of PCOs like cardiovascular disease (CVD) are consequences

In non-obese PCO patients, visceral fat distribution, waist to hip ratio (WHR), and abdominal obesity have relation with inflammatory situation. In one study, in lean PCOs, level of white blood cell (WBC) has a positive predictive value with insulin resistance, while the neutrophil to lymphocyte ratio has a negative predictive value [51]. Also, it has been demonstrated that in clomiphene citrate (CC)-resistant patients, regardless to BMI, inflammatory markers like TNFα are too high, and TNF-α serum level may be used as a clinical predictive indicator before CC

Even in lean PCO women, we can see higher waist to hip ratio, greater intra peritoneal and visceral fat, and percentage of body fat in comparison with BMI matched non-PCO women. Accumulation of small subcutaneous abdominal fat in those patients shows spoiled adipogenesis and hyperandrogenism [53]. Also, abnormal gene expression in stem cell of subcutaneous abdominal fat in normoandrogen and ovulatory lean PCO women display abnormal vacuolization and angiogenesis, which may reflect metabolism alter in those women [54]. From another side, adiponectin, a protein which is involved in regulating glucose levels and fatty acid breakdown, is produced by omental fat and dysregulated by high level of insulin; thus, even in lean PCOs women, inappropriate metabolism of glucose and lipid can be explained [55]. In respect with a new randomized controlled trial, arranged and regular physical exercise can ameliorate insulin sensitivity, hyperandrogenemia, and menstrual regularity in lean PCO

PCOs is considered by multiple metabolic disorders which may associate to increase risk of hypertension and cardiovascular disease. One study used menstrual irregularity as a predictive

from ovary [49].

of inflammatory state [50].

useless administration [52].

6. Weight and PCO

women [56].

7. Metabolic disorders and PCO

As mentioned before, in PCO women, insulin in a solitary manner or with synergetic effect of LH induces androgen production by ovaries. Even in lean PCOs women with normal metabolic insulin sensitivity and insulin levels, decline of insulin secretion with diazoxide (like metformin) prominently reduce levels of free T and androstenedione and meaningfully increased SHBG [36]. In these women, hyperandrogenemia is seen because of augmented sensitivity of their androgenic pathway to insulin and dysregulation of steroidogeneses enzymes based on genetic predisposition [37]. Therefore, even in PCOs patients with normal insulin metabolic and without clinical approved IR, local resistance in the ovaries increased androgens production [38].

Androgen excess or hyperandrogenemia (HA) in PCOs women contribute in exacerbation of metabolic abnormalities, such as insulin resistance in adipose tissue and skeletal muscle and elevation in lipid metabolism in visceral fat, decreased lipolysis in subcutaneous fat, increased low-density lipoprotein cholesterol (LDL-C) levels decreased HDL-C levels. Besides that, androgens may be involved in possible direct vascular action [39]. There are some studies, in which hyperandrogenemia was accompanying with metabolic syndrome (MetS) in non-obese PCOs more than obese PCOs women [40, 41].

Hyperandrogenemia or androgen access clinical signs are mainly cutaneous manifestations: hirsutism, acne, androgenic alopecia, acanthosis nigricans (AN), and seborrhea. In one study, their prevalence in PCOs women was: 78, 48, 31, 30, and 29% (in mentioned order) [42]. In another study, the prevalence of acanthosis nigricans in obese PCO was 42.5% compared to 28% in non-obese [43]. One published paper shows that AN is a marker of hyperinsulinemia in both obese and non-obese PCO patients rather than a sign of androgen excess and the only sex steroid associated with histological AN is dehydroepiandrosterone sulfate (DHEAS) [44].

Pharmacological management of hyperandrogenic skin symptoms has two targets: firstly, decrease the level of circulating androgens, and secondly prevent their effect at tissue level. Cyproterone acetate/ethinylestradiol has beneficial effect in non-obese PCO women with hyperandrogenic skin symptoms [45].
