Polycystic Ovary Syndrome

A woman that finds herself with irregular menstrual cycles, excess facial and body hair, adult acne, weight gain, infertility and enlarged ovaries may have polycystic ovary syndrome (PCOS), an unfortunate condition that afflicts 5-10 percent of women of child-bearing age and approximately 70-90 percent of women with irregular menstrual cycles (Azziz et al 2004). Among its many symptoms, PCOS causes hormonal imbalances, including elevated testosterone (male hormone) and estrogen (female hormone) levels, as well as increased insulin levels (Azziz 2006, Moran 2010).

Although PCOS is the most common female endocrine disorder in the United States, its cause remains unclear (McCartney 2004). Perhaps this is why “syndrome” is most commonly used in conventional medicine to describe PCOS since the word itself alludes to its varied signs and symptoms but does not indicate a precise cause of the condition.

However, research largely overlooked by mainstream medicine reveals a strong association between PCOS, obesity, and insulin resistance, including characteristic features of insulin insensitivity such as dyslipidemia (abnormality of metabolism of fats) and hypertension (Diamanti-Kandarakis 2007, Sasaki 2011).

If left untreated, women with PCOS often develop severe clinical manifestations, such as hirsutism (excess facial and body hair), adult acne, infertility, and depression (Diamanti-Kandarakis 2008, Drosdzol 2007). Women with PCOS are at significantly higher risk for developing cardiovascular disease (Teede 2010) and endometrial cancer (Chittenden et al 2009).

Integrative medicine recognizes the seriousness of PCOS, as well as the need to approach the management of PCOS as a disease of insulin resistance in order to offer hope to the millions of women who suffer from this disease. For example, metformin, an insulin sensitizing agent that also helps to reduce excessive androgen production, promotes weight loss, restores fertility, and enhances glucose metabolism in patients with PCOS, is drastically underutilized by conventional medicine for this disease. However, management strategies commonly used to control individual symptoms of PCOS are known to have a number of undesirable side effects (Pasquali 2011).

Fortunately, for the millions suffering with PCOS published clinical studies support the use of natural therapeutics, such as inositol and N-acetyl-cysteine (NAC), for controlling the symptoms and side-effects.

Symptoms of PCOS

One of the challenging aspects of diagnosing PCOS is that the signs and symptoms vary from person to person, in both type and severity. Frequently, PCOS symptoms are mistaken for other medical illnesses. However, common symptoms include:

Menstrual abnormality is the most widespread characteristic of PCOS. These include cycles longer than 35 days (fewer than eight menstrual cycles a year); failure to menstruate for four months or longer; and prolonged periods that may be scant or heavy (Ma 2010).

Excess androgen production: Increased androgen levels are a key feature of PCOS, and may result in excess facial and body hair (hirsutism), adult acne and male-pattern baldness (in women). Worth noting, however, is that the physical signs of androgen excess vary with ethnicity. As an example, the prevalence of hirsutism in PCOS patients is at least 40% in European and American females, yet is even more common in darker skin types, but women of Asian descent may not be affected (Lowenstein 2006).

Polycystic ovaries: Enlarged ovaries containing numerous small cysts can be detected by ultrasound. However, some women with polycystic ovaries may not have PCOS, while some women with the condition have ovaries that appear normal (Azziz 2004).

Other conditions associated with PCOS

Infertility: PCOS is the most common cause of female infertility. Many women with polycystic ovary syndrome experience infrequent ovulation or lack of ovulation altogether and may have trouble becoming pregnant, PCOS also is associated with spontaneous abortion and preeclampsia (van der Spuy 2004).

Obesity: Compared with women of similar age who don’t have polycystic ovary syndrome, women with PCOS are significantly more likely to be overweight or obese (Martínez-Bermejo 2007, Moran 2010). Furthermore, about half of all women with PCOS manifest central obesity, in which there is a greater deposition of visceral fat around internal organs in the abdominal region, as opposed to the fat being located on the thighs and hips. Abdominal fat distribution is associated with increased risk of hypertension, diabetes and lipid abnormalities (Faloia 2004).

Insulin resistance and type 2 diabetes: Studies have found that women with PCOS have higher incidences of insulin resistance and type 2 diabetes than age and weight-matched controls (Moran 2010). Moreover, a majority of obese PCOS women and more than half of those of normal weight are insulin resistant (Pasquali 2006), and a significant number develop type 2 diabetes mellitus by the age of 40 (Pelusi 2004).

Acanthosis nigricans is a dark, poorly defined, velvety hyperpigmentation found on the nape of the neck, armpits, inner thighs, vulva, or under the breasts. This condition is a sign of insulin resistance, which leads to higher circulating insulin levels. Insulin spillover into the skin results in hyperplasia, an abnormal increase in skin growth (Higgins 2008).

Diagnosis of PCOS

There’s no specific test to definitively diagnose polycystic ovary syndrome. The diagnosis is one of exclusion, which means the doctor considers all signs and symptoms to rule out other possible disorders (Azziz 2004). A standard diagnostic assessment for PCOS includes a full medical history, at which time a doctor will consider irregular or absent periods, obesity, hirsutism (coarse facial and body hair), and poor breast development. During a physical exam, doctors typically look for physical signs of PCOS like acne, facial hair, male pattern baldness and acanthosis nigricans.

A pelvic or transvaginal ultrasound is used to detect “follicular arrest”, or the development of small (5–7mm) follicles that never reach the pre-ovulatory size of 16 mm or more. Though not all women with PCOS have polycystic ovaries (PCO), nor do all women with ovarian cysts have PCOS (Artini 2010), ultrasonographic scanning has substantially broadened the phenotypic spectrum of PCOS (Azziz 2004).

Diagnostic criteria published by the Androgen Excess Society in 2006 require the presence of clinical or biochemical hyperandrogenism, with either menstrual dysfunction or polycystic ovarian morphology (PCOM), which are detected via transvaginal ultrasonography (Artini 2010).

Blood work is used to measure the levels of several hormones and to exclude the many possible causes of menstrual abnormalities or androgen excess that mimic PCOS. Along with tests used to measure elevated androgen levels, doctors may look for high levels of lutenizing hormones (LH) or an elevation in the ratio of LH to follicle stimulating hormones (FSH), prolactin, thyroid stimulating hormone (TSH), 17-hydroxyprogesterone, testosterone and DHEA-S. Other associated conditions such as high levels of glucose, insulin, cholesterol and triglycerides, as well as insulin resistance may also be assessed (Shi 2007).

Some doctors now screen for high levels of Anti Mullerian Hormone (AMH) since it is considered a potential diagnostic marker for PCOS (Chen 2008, Dewailly 2010). AMH is a protein released by cells that are involved with the growth of the egg follicle. AMH levels correlate with the number of antral follicles (small follicles that are 2 to 8 mm in size and appear in the beginning of the menstrual cycle) found on the ovary; the higher the antral follicle count, the higher the AMH levels (van Houten 2010). Women with PCOS typically have a high number of antral follicles; they have correspondingly high AMH levels as well (Pellatt 2010).

Causes and risk factors for PCOS

PCOS was once regarded solely as a reproductive disorder affecting women of child-bearing age. Anovulation (a menstrual cycle in which ovulation does not occur) and androgen excess have been considered the hallmark diagnostic criteria of the syndrome (Azziz 2004). However, insulin resistance is now identified as a significant contributor to the pathogenesis of PCOS, the metabolic and cardiovascular consequences of which are widely acknowledged within the scientific community (Pasquali 2011). To date, several factors involved in the development of PCOS have been identified:

LH Secretion and Androgen Excess: Past research has emphasized the role of neuroendocrine abnormalities in the persistent and excessive secretion of luteinizing hormones (LH), one of two glycoprotein hormones that stimulate the final ripening of the follicles and the secretion of progesterone. Excessive LH triggers premature ovulation, disrupting the follicle’s maturation process and leading to an increase in androgen production by ovarian theca cells. Some research points to increased LH as the driving force for PCOS in slender and normal body-weight women (Chang 2000).

Hyperinsulinemia and Androgen Excess: Hyperinsulinemia produces hyperandrogenism in women with PCOS via two distinct and independent mechanisms:

First by stimulating ovarian androgen production. Studies have shown that insulin acts synergistically with LH to enhance androgen production in ovarian theca cells (Guzick 2004, Tsilchorozidou 2004; and Second by directly and independently reducing serum sex hormone-binding globulin (SHBG) levels. Insulin decreases hepatic synthesis and SHBG secretion, thus increasing the amount of free, biologically active testosterone (Carmina 2003). The net result of these two actions increases circulating free testosterone concentrations.

Genetics and Androgen Excess: An increase in LH, as well as hyperinsulinemia, leads to an increase in androgen production by ovarian theca cells (Tsilchorozidou 2004). Research indicates that morphological changes in the ovaries, including ovarian cyst development and theca-cell (steroid-producing cells in the ovaries) dysfunction, may be an indication of a genetic basis for PCOS. Researchers suspect there is a genetically determined ovarian defect present in women with PCOS, causing the ovary to overproduce androgen (Tsilchorozidou, 2004, Jakubowski 2005, Diamanti-Kandarakis 2006, Bremer 2008). Indeed, abnormal theca cell activity seems to be a primary source for excess androgens (Wood 2003).

The following risk factors are also thought to have a strong influence over the progression of PCOS.

Obesity. Studies have found that obesity not only contributes to the development of PCOS, but arises also as a result (Martínez-Bermejo 2007). The adipose tissue of women with PCOS is characterized by enlarged fat cells (hypertrophic adipocytes) and impairments in the body’s ability to break down fat (lipolysis) and regulate insulin. Whether these abnormalities are primary or secondary to hyperandrogenism or other PCOS-related abnormalities is not yet known (Villa 2011).

Age at onset. Some research suggests that girls who develop pubic hair early (often before the age of eight, and a condition known as premature pubarche) have many of the signs and symptoms of PCOS. In one study that followed pre-pubescent girls throughout puberty, premature pubarche resulted in excess testosterone production and irregular periods consistent with PCOS, leading researchers to conclude that premature pubarche may be an early form of PCOS (Witchel 2006).

Other risk factors that may play a role in the pathogenesis of PCOS include chronic inflammation (Escobar-Morreale 2011); exposure to endocrine-disrupting chemicals (Takeuchi 2004); autoimmune disorders, especially those involving the ovaries, pancreas, thyroid and adrenal glands (Petríková 2010); and the use of medications that increase prolactin production (Hernández 2000).

Laying aside etiology, women with PCOS are prone to defects in insulin signaling, which aggravates the synthesis of androgens in the ovaries and adrenal gland (Tsilchorozidou 2004). Excess androgens encourage insulin resistance, leading to elevated insulin levels, which in turn stimulate further androgen synthesis. This vicious cycle results in a “snowball effect” worsening PCOS symptoms and making sufferers especially susceptible to obesity and diabetes, conditions that significantly compound the syndrome’s progression (Schuring 2008, Pasquali 2011).

What You Need to Know

  • Polycystic Ovary Syndrome is a common female endocrine disorder.
  • Though symptoms vary from person to person, it is characterized by multiple ovarian cysts, irregular, heavy or non-existent periods, excessive facial/body hair, male pattern baldness, decreased sex drive, skin tags, infertility, depression and weight gain.
  • Insulin resistance is one of the most common features of PCOS, and a condition in which the cells of the body literally become resistant to the effects of insulin.
  • The root cause of PCOS is unknown but genetic predisposition, insulin resistance, excess androgen production, and obesity all play a role.
  • Since the symptoms of PCOS vary in severity and form, many treatments are used. Conventional options include drug treatments for hirsutism and acne; drugs such as clomifenem tamoxifen and gonadotrophins to induce ovulation for infertility; surgery to induce ovulation by reducing androgen levels, and promising insulin-sensitizing drugs such as metformin.
  • The most important aspect of long term care of PCOS is managing cardiovascular risks such as obesity, insulin resistance, diabetes, hypertension and elevated blood cholesterol, early recognition and intervention are considered to be the cornerstones of PCOS treatment.
  • Emerging evidence suggests that lifestyle choices such as weight reduction and exercise, along with a specific nutraceuticals targeted to safely and effectively deal with symptoms, underlying causes and associated risk factors, might help reduce the incidence and severity of PCOS.

Conventional treatment of PCOS

Polycystic ovary syndrome treatment generally focuses on management of the individual main concerns, such as infertility, hirsutism, acne or obesity.

Hirsutism:

  • Oral contraceptive pills, estrogen–progesterone combinations, are preferably used. Estrogens lower LH levels and androgen production; Progesterone is crucial, as it may increase the liver production of SHBG, reducing free testosterone levels (Kopera 2010).
  • Another medication called spironolactone (Aldactone®) is used as a primary medical treatment for hirsutism and female pattern hair loss since the accidental discovery of its antiandrogenic effects. Spironolactone reduces testosterone production and inhibits its action on target tissues. It also is an effective alternative treatment for acne in women. Spironolactone should not be used in pregnancy since it can disturb the growth and development of the embryo and fetus (Rathnayake 2010).
  • Even more promising are insulin-sensitizers like metformin (see text box below), which also holds promise for managing hirsutism in PCOS patients (Kopera 2010).

Infertility:

Ovulation induction remains a milestone in the treatment of women with anovulatory infertility (Badaway 2011).

 

  • Clomiphene citrate (CC), an oral anti-estrogen medication, is considered the first line treatment for inducing ovulation in women with PCOS (Badaway 2011).
  • Since insulin resistance plays a central role in PCOS, insulin reduction strategies are a possible treatment for infertility in PCOS patients (Fica 2008). For instance, if CC alone isn’t effective, metformin can be added to help induce ovulation (Abu Hashim 2010).
  • If the CC and metformin combination fails, gonadotropins — follicle-stimulating hormone (FSH) and luteinizing hormone (LH) medications that are administered by injection—may be another option (Nugent 2000, Badaway 2011).
  • Aromatase inhibitors, such as anastrozole and letrozole, are a relatively new treatment for ovulation induction (Polyzos 2009). Aromatase inhibitors selectively block the peripheral conversion of androgens to estrogens, causing a reaction in the pituitary gland, increasing FSH, and optimizing ovulation. The advantage of aromatase inhibitors is that they avoid the unfavorable side-effects seen frequently with antiestrogens (Mitwally, 2001).
  • If medication does not work, a surgical procedure called laparoscopic ovarian drilling (LOD) may be considered. During LOD, a surgeon makes a small incision in the abdomen and inserts a tube attached to a tiny camera (laparoscope) providing detailed images of the ovaries and neighboring pelvic organs. The surgeon then inserts surgical instruments through other small incisions and uses electrical or laser energy to destroy the extra, androgen producing follicles on the surface of the ovaries. The goal of the operation is to induce ovulation by reducing androgen levels.

Regulation of the menstrual cycle:

  • Metformin improves ovulation and leads to regular menstrual cycles (see side bar).
  • Birth control pills containing a combination of synthetic estrogen and progesterone decrease androgen production, correct abnormal bleeding, and decrease the risk of endometrial cancer as well. Low-dose birth control pills have been proven effective for regulating the menstrual cycles of those who are not trying to become pregnant (Cianci 2007).
  • To date, there are no known clinical studies on bio-identical hormone replacement therapy (BHRT) and PCOS

Long term PCOS management:

  • Managing cardiovascular risks such as obesity, elevated cholesterol, high blood pressure and diabetes is considered the most important aspect of PCOS treatment.
  • Since medications such as metformin and thiazolidinedione improve insulin sensitivity, in 2004 Great Britain’s National Institute for Health and Clinical excellence recommended that women with PCOS that have a BMI above 25 be given metformin when other therapies fail to produce results (National Institute for Health and Clinical Excellence 2004).
  • This recommendation proved to be well-founded, as Metformin is known to be an effective treatment for both hyperinsulinemia and hyperandrogenism (Azzia 2001, Romualdi 2011, Yasmin 2011).
  • Indeed, metformin may be the most promising conventional medical treatment for PCOS.

Metformin: An Underutilized Treatment for PCOS

  • Metformin is a medication currently used to lower blood sugar and approved by the US Food and Drug Administration (FDA) to manage type 2 diabetes mellitus. Metformin inhibits liver glucose production, though it also decreases intestinal glucose uptake and increases insulin sensitivity in peripheral tissues (Grundy 2002).
  • Metformin improves the likelihood of ovulation in women with PCOS through a variety of actions, including reducing insulin levels and altering the effect of insulin on ovarian androgen synthesis, theca cell proliferation, and endometrial growth (Badawy 2011).
  • To increase metformin tolerance, patients start with 500 mg daily with food. After one week, the dose increases to 1000 mg for another week and then to 1500 mg daily. Clinical response is usually seen at the 1000 mg daily dose (Harborne 2005).
  • Studies have found that PCOS patients who do not respond to metformin at the 1500 mg dose, respond favorably to 2000 mg (Harborne 2005).
  • For many years, oral hypoglycemic agents were regarded as teratogenic, and their use was contraindicated during pregnancy. However, the latest data supports the safety of metformin throughout pregnancy. Glueck et al reported that metformin was not teratogenic and did not affect the motor or social development of infants age 3 and 6 months (Glueck 2002). Recently, Tang et al concluded that metformin improves ovulation and pregnancy rates, findings they noted while updating the Cochrane Review of insulin-sensitizing drugs (metformin, rosiglitazone, pioglitazone, d-chiro-inositol) for women with PCOS, oligo/amenorrhea and subfertility (Tang 2010).
  • A recent clinical study of 50 PCOS patients reported that metformin exerts a slight but significant deleterious effect on serum homocysteine levels. Therefore, supplementing with folate is considered useful for lowering homocysteine and increasing the beneficial effect of metformin on the vascular endothelium (the inner lining of the blood vessels)(Palomba 2010).

Side Effects with Conventional Treatments

A pitfall of mainstream approaches to PCOS is that they are often associated with unwanted side effects, for example:

  • For trouble conceiving, a doctor typically prescribes fertility drug Clomid®. In some women, Clomid® causes no side effects. In others, side effects may include mood swings, hot flashes, breast tenderness, abdominal cramps, and nausea. Roughly 30 % of women who take Clomid® experience the more serious side effects of hostile fertile mucous (HFM, a condition in which the cervical mucus become too thick to allow sperm to penetrate the cervix) and uterine lining thinning. HFM prevents conception and a thin uterine lining decreases the likelihood of implantation and may lead to early miscarriage, both are undesirable effects of using Clomid®.
  • Birth control pills are still the treatment of choice for irregular periods. However, a 2006 study concluded that birth control pills increase insulin resistance, making the symptoms of PCOS more pronounced and increasing the risk of major heath complications (Mastorakos 2006).
  • In fact, many medications used in the treatment of PCOS do not adequately address the lifestyle and hormonal imbalances that are at the root of PCOS, nor do they hold much promise for managing associated cardiovascular risks and type 2 diabetes.

PCOS Nutritional Protocol

Inositol

“Inositol” is a term used to refer to a group of naturally occurring carbohydrate compounds that exist in nine possible chemical orientations called stereoisomers. The most common being myo-inositol, which is often sold as a dietary supplement labeled simply as inositol.

Inositol, particularly myo-inositol and another less common stereoisomer called D-chiro-inositol, plays a critical, but underappreciated, role in insulin signaling. Conditions such as hyperglycemia and diabetes are associated with disrupted inositol signaling, leading many researchers to suggest that this may be a key pathologic feature of insulin resistance (Manning 2010, Larner 2010).

Research has shown that the three inositol family members help to ameliorate conditions in which insulin resistance plays an important role, especially PCOS.

D-chiro-inositol (DCI)

D-chiro inositol is perhaps the most promising inositol compound for PCOS. Our bodies produce D-chiro-inositol only after extensive inositol metabolism. DCI interacts with select sugars in the body to form conjugates known as inositiol phosphoglycans, which play a key role in mediating insulin actions. Low levels of DCI, and inositol phosphoglycans have been observed in individuals with impaired insulin sensitivity and PCOS (Susuki 1994, Jung 2005, Cheang 2008, Baillargeon 2010).

In one study, 44 overweight women with PCOS were given a daily 1,200mg dose of D-chiro inositol for six to eight weeks. During the course of the study, those who took DCI displayed significant improvements in insulin sensitivity, blood pressure, and triglyceride levels, as well as a marked decrease in serum testosterone levels. Moreover, 19 of 22 subjects receiving DCI ovulated during the study period, compared to only 6 of 22 in the placebo group. The investigators concluding statement highlights the efficacy of DCI in PCOS: “D-Chiro-inositol increases the action of insulin in patients with the polycystic ovary syndrome, thereby improving ovulatory function and decreasing serum androgen concentrations, blood pressure, and plasma triglyceride concentrations.” (Nestler 1999).

Similarly promising results were drawn from another study involving lean women with PCOS. Here, participants received 600 mg daily of DCI or a placebo for six to eight weeks. The DCI-treated participants improved significantly, displaying a large decrease of 73% in testosterone levels versus no change in the placebo group. Women taking DCI also experienced reductions in insulin and triglyceride levels and blood pressure, whereas none of these changes were evident in the placebo group (Luorno 2002).

Researchers looking at the effects of metformin in PCOS women concluded that the drug’s benefits could be related to its ability to improve the function of DCI phosphoglycans in the body. Thus, it appears that DCI may be highly effective when used in combination with metformin for PCOS (Baillargeon 2004).

Myo-inositol

Myo-inositol is a stereoisomer of DCI. Like DCI, it is a key factor in insulin signaling, and serves also as a precursor to DCI in endogenous inositol metabolism. It should then come as no surprise that studies using myoinositol in women with PCOS produced results as promising as those obtained with DCI.

Double-blind, placebo-controlled investigations were carried out in 42 women with PCOS, subjects receiving myo-inositol fared much better when compared to the placebo group, displaying decreases in testosterone, triglycerides, and blood pressure; a significant improvement in insulin sensitivity; and a greatly increased frequency of ovulation (Costantino 2009).

In another study, 20 women with PCOS were given either 2 grams of myo-inositol plus 200 mcg folic acid, or a placebo of 200 mcg folic acid daily. After 12 weeks, the women taking myo-inositol showed improved insulin sensitivity and androgen levels. Strikingly, all the subjects receiving myo-inositol returned to normal menstrual cycles (Genazzani 2008).

In an Italian study of 92 PCOS patients, almost 50% showed significant weight loss and reduced leptin levels after receiving myo-inositol plus folic acid (4 g myo-inositol plus 400 mcg folic acid). After a 14-wk treatment, the myo-inositol plus folic acid group lost weight, whereas the placebo group gained weight (Gerli 2007).

A six-month study involving 50 PCOS women yielded similar results and gave researchers the time to evaluate the effects of myo-inositol on hirsutism. Along with decreases in testosterone and insulin levels, the participants who supplemented with myo-inositol experienced a reduction in hirsutism, and improvements in skin appearance, leading researches to conclude, “Myoinositol administration is a simple and safe treatment that ameliorates the metabolic profile of patients with PCOS, reducing hirsutism and acne.” (Zacchè 2009).

In other well-designed clinical trials for follicular maturity and ovulation induction, myoinositol has produced promising results, cementing its position as a novel therapy for PCOS management (Papaleo 2007, Papaleo 2009).

D-pinitol

D-Pinitol is 3-O-methyl-D-chiro-inositol that occurs naturally in several different foods, including legumes and citrus fruits (Kang 2006). D-Pinitol is converted into d-chiro-inositol in the body. Like d-chiro-inositol, pinitol appears to favorably influence the action of insulin (Bates 2000). In a double-blind study of patients with type 2 diabetes administration of 600 mg of pinitol twice a day for three months reduced blood glucose concentration by 19.3%, decreased hemoglobin A1C (HbA1C) concentration by 12.4% and significantly improved insulin resistance (Kim 2004). In a shorter-term double-blind study, administration of pinitol at a dose of 20 mg per kg of body weight per day for four weeks decreased mean fasting plasma glucose concentration by 5.3% (Kim 2005).

N-acetyl cysteine (NAC)

N-acetyl-cysteine (NAC) is a stable derivative of the sulfur-containing amino acid cysteine and an antioxidant that is needed for the production of glutathione, one of the body’s most important natural antioxidants and detoxifiers. While cysteine is found in high protein foods, n-acetyl cysteine is not. A large body of evidence supports the use of NAC in women with PCOS.

  • Improving Insulin Sensitivity
    Women with PCOS frequently have an abnormally high insulin response to sugars and refined starches. A 2002 study evaluated the effect of NAC on insulin secretion and peripheral insulin resistance in women with PCOS (Fulghesu 2002). The study subjects who had an exaggerated insulin response to a glucose challenge and were treated with NAC showed an improvement in insulin function in their peripheral tissues. The NAC treatment also produced a significant decline in testosterone levels and in free androgen index values. The researchers concluded, “NAC may be a new treatment for the improvement of circulating insulin levels and insulin sensitivity in hyperinsulinemic patients with polycystic ovary syndrome.” (Abu 2010)
  • Restoring Fertility
    NAC may also be useful for improving fertility in women with PCOS. In one study, NAC appeared to improve the effects of Clomid®, the widely used fertility drug. Clomid® plus NAC significantly improved ovulation rates in a study of 573 women with PCOS. According to the researchers, 52% of the study participants who took Clomid® plus NAC ovulated, whereas only 18% ovulated in the Clomid® alone group. The authors concluded: “N-Acetyl cysteine is proved effective in inducing or augmenting ovulation in polycystic ovary patients.” (Badawy 2007).

Similarly, a study of Clomid®-resistant women has shown that NAC appears to make Clomid® more effective. In the study, 150 Clomid®-resistant women with PCOS were divided into two groups: one group took Clomid® and NAC. The other group took Clomid® and a placebo. In the NAC group, 49.3% ovulated and 1.3% became pregnant. In contrast, in the placebo group, only 21% ovulated and there were no pregnancies (Rizk 2005).

Worth noting, the same researchers compared the effects of a NAC- Clomid® combination with the metformin- Clomid® combination on ovulation induction in anovulatory Clomid®-resistant women with PCOS. The efficacy of the metformin- Clomid® combination therapy is significantly higher than that of NAC- Clomid® for inducing ovulation and achieving pregnancy among Clomid®-resistant PCOS patients (Abu 2010).

  • Tackling Homocysteine
    Women with PCOS are often given metformin to deal with their insulin problems. But metformin may increase homocysteine levels and many women with PCOS have high homocysteine levels to begin with (Badaway 2007). Elevated homocysteine is associated with coronary artery disease, heart attack, chronic fatigue, fibromyalgia, cognitive impairment, and cervical cancer. A 2009 study showed that people taking NAC for two months had a significant decrease in homocysteine levels (Rymarz 2009).

Magnesium

Many women with PCOS have significantly low serum and total magnesium, contributing to the progression of insulin resistance to type 2 diabetes and heart disease (Kauffman 2011).

Magnesium insufficiency is common in poorly controlled type 2 diabetes patients. In one study, 128 patients with poorly controlled type 2 diabetes received a placebo or a supplement with either 500 mg or 1000 mg of magnesium oxide (300 mg or 600mg element magnesium) for 30 days. All patients were treated also with diet or diet plus oral medication to control blood glucose levels. Magnesium levels increased in the group receiving 1,000 mg magnesium oxide daily but did not significantly change in the placebo group or the group receiving 500 mg of magnesium. The author suggested prolonged use of magnesium in doses that are higher than usual is needed in patients with type 2 diabetes to improve control or prevent chronic complications (De Lourdes Lima 1998).

In a related study, 63 diabetics with below normal serum magnesium levels received either 2.5 grams of oral magnesium chloride daily (providing 300 mg elemental magnesium per day) or a placebo. At the end of the 16-week study period, those who received the supplement had higher blood levels of magnesium and improved control of diabetes, as suggested by lower hemoglobin A1C (HbA1C) levels (Rodriguez-Moran 2003).

Another study found that oral magnesium supplements helped insulin resistant individuals avoid developing type 2 diabetes (Mooren 2011).

Since magnesium improves insulin-mediated glucose uptake and insulin secretion in type 2 diabetes patients, it is considered a critical mineral for women with PCOS.

Chromium

Research shows a clear link between chromium and glucose metabolism. Indeed, chromium is one of the most widely studied nutritional interventions in the treatment of glucose and insulin-related irregularities. Chromium picolinate specifically is the form that has been used in a number of studies on insulin resistance. Researchers at the University of Texas Health Science Center at San Antonio found that chromium picolinate (200 μg/d) improves glucose tolerance when compared with a placebo (Lucidi 2005) in women with PCOS.

Lipoic Acid

Overwhelming evidence suggests that lipoic acid may be critical not only for maintaining optimal blood sugar levels (by helping the body use glucose), but also for supporting insulin sensitivity and key aspects of cardiovascular health, such as endothelial function. A review of experimental studies reveals that lipoic acid helps relieve several components of metabolic syndrome—a constellation of risk factors that often precedes full-blown type 2 diabetes. It appears that lipoic acid reduces blood pressure and insulin resistance, improves lipid profile, and reduces weight. Based on the results of key clinical studies, scientists are sanguine about lipoic acid’s potential as a therapeutic agent for individuals with metabolic syndrome (Pershadsingh 2007). Similarly positive effects have been observed in women with PCOS. In a 16-week study, women with PCOS were given 600 mg of lipoic acid twice daily, and, over the course of the study period, exhibited a sharp improvement in insulin sensitivity, and a reduction in triglycerides. Lipoic acid therapy also is associated with an improved LDL-particle pattern (or “bad” cholesterol particles), indicating a reduction in cardiovascular risk (Masharani 2010).

Vitamin D

In an insightful associative study that highlighted the link between PCOS and vitamin D status, researchers found that women with higher blood levels of vitamin D were much less likely to be insulin resistant (Wehr 2011). A separate study found that vitamin D when administered with metformin was helpful for regulating the menstrual cycles in PCOS women (Rashidi 2009).

A study conducted by researchers at Columbia University found that Vitamin D combined with calcium supplementation helped normalize menstrual cycles for seven of 13 women with PCOS. Of the seven, two became pregnant and the others maintained normal menstrual cycles. These results suggest that abnormalities in calcium balance may be responsible, in part, for the arrested follicular development in women with PCOS and contribute to its pathogenesis (Thys-Jacobs 1999).

Omega-3 Fatty Acids

Evidence suggests that the anti-inflammatory activity of omega-3 fatty acids ameliorates non-alcoholic fatty liver disease, a common condition in women with PCOS. In an Australian study, omega-3 fatty acid supplementation reduced liver fat content and other cardiovascular risk factors in women with PCOS, including triglycerides, and systolic and diastolic blood pressure. In particular, said the researchers, omega-3 fatty acids were helpful in reducing hepatic fat in PCOS women with hepatic steatosis, which is defined as liver fat content greater than 5% (Cussons 2009).

Flaxseeds

The powerful lignans—plant compounds that have both estrogenic and antiestrogenic properties—in flaxseed may help reduce androgen levels in PCOS women. Flaxseed consumption have been shown to stimulate sex hormone-binding globulin (SHBG) synthesis (Shultz 1991). Changes in SHBG concentration result in relatively large changes in the amount of free and bound hormones.

In a 2007 study, daily flaxseed supplementation reduced androgen levels and hirsutism in PCOS patients, leading researchers to conclude, “The clinically-significant decrease in androgen levels with a concomitant reduction in hirsutism reported in this case study demonstrates a need for further research of flaxseed supplementation on hormonal levels and clinical symptoms of PCOS.” (Nowak 2007).

Cinnamon

Scientists at the US Department of Agriculture (USDA) have been studying the effect of cinnamon on blood glucose for over a decade, leading to several interesting discoveries, including that of unique compounds in cinnamon bark that in laboratory studies produce a 20-fold increase sugar metabolism (Broadhurst 2000, Cao 2010). According to one government expert, “These polyphenolic polymers found in cinnamon may function as antioxidants, potentiate insulin action, and may be beneficial in the control of glucose intolerance and diabetes.” (Anderson 2004).

In a 2003 study, 60 diabetics taking 1, 3, or 6 grams/day of ground cinnamon for 40 days lowered their fasting serum glucose by 18% to 29%; triglycerides by 23% to 30%; LDL cholesterol by 7% to 27%; and total cholesterol by 12% to 26% (Khan 2003).

A 2007 study by researchers at Columbia University found that cinnamon reduced insulin resistance in fifteen women with PCOS. In the study, the women were divided into two groups: one group took cinnamon extract while the other group took a placebo. After 8 weeks, the cinnamon group showed significant reductions in insulin resistance while the placebo group did not. The authors did point out that, “A larger trial is needed to confirm the findings of this pilot study and to evaluate the effect of cinnamon extract on menstrual cyclicity.”(Wang 2007).

Licorice Root

A 2004 study by Italian researchers investigated the effect of licorice on androgen metabolism in nine healthy 22-26 year old women in the luteal phase of their menstrual cycle and found that licorice reduces serum testosterone. The authors suggested that licorice could be considered an “adjuvant therapy of hirsutism and polycystic ovary syndrome. This study was the first to follow up on earlier trials, which found that an herbal formula containing licorice reduced testosterone secretion in women with polycystic ovary syndrome (Armamani 2004, Takahashi 1988, Takeuchi 1991).

Spironolactone (Aldactone), an antagonist of mineralocorticoid and androgen receptors, is used as a primary medical treatment for hirsutism and female pattern hair loss. It is also associated with several side effects related to the diuretic activity of spironolactone. Interestingly, licorice was shown in a study of women with PCOS to counteract the side-effects of spironolactone when the two were used in combination (Armanini 2007).

Green Tea: (epigallocatechin gallate, EGCG)

Green tea may be of benefit to women with PCOS. Green tea is known to have positive effects on glucose metabolism (Tsuneki 2004). In both human and animal studies, green tea has been shown to improve insulin sensitivity (Potenza 2007, Venables 2008). Animal research suggests that green tea epigallocatechin gallate (EGCG) may help prevent the onset of type 2 diabetes and slow its progression (Wolfram 2006). A clinical study from Japan found that daily supplementation of green tea extract lowered the hemoglobin A1C (HbA1C) level in individuals with borderline diabetes (Fukino 2008). Hemoglobin A1C is a form of hemoglobin that is used to help identify plasma glucose concentration over a period of time.

Green tea also is thought to lower TNF-alpha (Ivanov 2006). TNF-alpha or tumor necrosis factor is involved with systemic inflammation. Green tea is a potent antioxidant and, a study in the American Journal of Clinical Nutrition showed that just 90 mg of EGCG before each meal increased the body’s 24-hour metabolism rate by 4% and the metabolism of fat by an impressive 40% (Dulloo 1999).

Spearmint

A recent study by British researchers published in the journal Phytotherapy Research found a positive link between spearmint tea consumption and a reduction in hirsutism in PCOS women. In the study, 42 women were divided into two groups: one that took spearmint tea twice a day for a 1-month period and the other a placebo herbal tea. The spearmint tea group showed significant decreases in free and total testosterone levels and an increase in LH and FSH, leading the researchers to conclude that “spearmint (tea) has the potential for use as a helpful and natural treatment for hirsutism in PCOS.” (Grant 2010).

Saw Palmetto

Saw palmetto inhibits the activity of an enzyme, 5-alpha reductase, thereby reducing the conversion of testosterone to dihydrotestosterone, the more androgenic form of male hormone. This may have implications for reducing acne, excess facial and body hair, as well as male pattern hair loss. Oral administered saw palmetto has been studied as part of a formula that slowed hair loss and improved hair density in patients with testosterone related hair loss (Prager, 2002).

Life Style and Diet Changes Recommendation

For women with polycystic ovary syndrome, daily physical activity and participation in a regular exercise regimen are essential for treating or preventing insulin resistance, lowering blood sugar levels and for helping weight-control efforts.

Since a majority of PCOS women are obese, and insulin resistance plays a critical role in the development of PCOS, a diet that is high in fiber, low in saturated fatty acids and monounsaturated fat, and high in vitamins, minerals and disease fighting phyto-nutrients may reduce certain risk factors and improve overall wellbeing.

Additional research may determine which specific dietary approach is best for PCOS, but it’s clear that losing weight by reducing total caloric intake benefits the overall health of women with polycystic ovary syndrome.

A clinical study, short-term treatment of obese PCOS women on a ultra low calorie diet (350-450 kcal per day) decreased androgen signaling and reduced serum insulin (Kiddy 1992).

A study by Italian researchers concluded that comprehensive dietary change designed to lower insulin resulted in a significant decrease in testosterone, body weight, waist/hip ratio, total cholesterol, fasting blood glucose and insulin (Berrino 2001).

Diets high in monounsaturated fats have been shown to increase insulin sensitivity and lower the overall glycemic index. High fiber foods are slowly absorbed, causing less insulin to be released; High fiber diets increase SHBG, which binds to and lowers free testosterone; Fibers also can lower PAI-1 (plasminogen activator inhibitor, a glycosylated protein that plays a significant role in metabolic syndrome) as well as cholesterol and blood lipids (Kiddy 1992).

A study reported that just a moderate reduction in dietary carbohydrates reduced fasting and post-challenge insulin concentrations among women with PCOS, improving reproductive/endocrine outcomes (Douglas 2006). Echoed a 2005 report, “On the balance of evidence to date, a diet low in saturated fat and high in fiber from predominantly low-glycemic-index-carbohydrate foods is recommended [in the dietary management of PCOS]” (Marsh 2005).

Life Extension Recommendations

PCOS Safety Caveats

Chromium Picolinate

Because chromium may lower blood glucose, consult your healthcare provider before taking this product if you are taking blood glucose lowering medication.

N-acetyl-cysteine (NAC)

Those who supplement with NAC should drink 6 to 8 glasses of water daily in order to prevent cysteine renal stones. Cysteine renal stones are rare but do occur.

Licorice Root

People with heart problems, conditions affected by estrogen, liver and/or kidney disease, or severe muscle spasms should consult a doctor before taking licorice. Licorice is not recommended for use during pregnancy. Consult your doctor before taking licorice if you’re taking corticosteroids, mineralocorticoids, warfarin, or diuretics.

Lipoic acid

If you are sensitive to changes in blood sugar and/or being treated for diabetes with blood sugar–lowering drugs, please consult with your physician before supplementing with lipoic acid. In this context, start with a low dose and assess for effect. Inform your physician should you notice any changes while taking lipoic acid.

Magnesium

If taken in high doses, magnesium may have a laxative effect. If this occurs, divide dosing, reduce intake, or discontinue product.

Vitamin D

Individuals consuming more than 2,000 IU/day of vitamin D (from diet and supplements) should periodically obtain a serum 25-hydroxy vitamin D measurement. Do not exceed 10,000 IU per day unless recommended by your doctor. Vitamin D supplementation is not recommended for individuals with hypercalcemia (high blood calcium levels). People with kidney disease, certain medical conditions (such as hyperparathyroidism or sarcoidosis), and those who use cardiac glycosides (digoxin) or thiazide diurectics should consult a physician before using supplemental vitamin D.

Fish Oil

If you are taking anti-coagulant or anti-platelet medications, or have a bleeding disorder, consult your healthcare provider before taking fish oil.

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