Polycystic Ovary Syndrome (PCOS)

PCOS stands for Polycystic Ovary Syndrome, but it is not actually exclusively defined by ovarian cysts. PCOS is the most frequent endocrine condition in premenopausal women is (PCOS). The global prevalence of this illness ranges from 6% to 20% depending on the diagnostic criteria used, with a higher prevalence among overweight or obese women and among ethnic groups.[1,2,3,4]

PCOS is a complicated endocrine condition characterized by clinical or biochemical hyperandrogenism, ovarian dysfunction (menstrual irregularities), and polycystic ovarian morphology, among other issues. There is currently a plethora of PCOS diagnosis criteria that include various combinations of its clinical features. The Rotterdam criteria, which is mostly employed for clinical diagnosis, require at least two of the three clinical characteristics listed above.[5]

PCOS is regarded as a major cause of anovulatory infertility and is therefore clinically linked to subfertility or infertility.[6]. However, the pathology’s negative impact is not limited to reproductive function. PCOS is also connected to numerous metabolic problems such as obesity and insulin resistance (IR).[7] A considerable number of women with PCOS are overweight, and they often have IR with hyperinsulinemia.[8,9] IR is the most prevalent metabolic perturbation in women with PCOS, affecting 65–70% of all patients. Notably, IR and hyperinsulinemia are metabolic features shared by most slim women with PCOS as well. Hyperinsulinemia also contributes to the development of various phenotypic aspects of PCOS. In conjunction with BETA cell dysfunction, it increases the likelihood of developing other metabolic problems such as type 2 diabetes (T2D), hypertension dyslipidemia, and cardiovascular disease. The frequency of these metabolic comorbidities is high in overweight women with PCOS, mostly due to hormonal imbalances such as elevated luteinizing hormone (LH) and normal or suppressed follicle stimulating hormone (FSH) resulting in an altered LH/FSH ratio.[10]

The clinical features of hyperandrogenism are also related to hyperinsulinemia and insulin resistance.
While many elements of PCOS pathogenesis remain unknown, it is believed that hyperandrogenism contributes significantly to the development of many of the reproductive and metabolic abnormalities associated with PCOS. Excess androgen has a detrimental effect on metabolic balance in women with PCOS, affecting a variety of metabolic tissues, including adipose tissue, liver, muscle, pancreas, and the brain. Androgen synthesis in ovarian theca cells is stimulated by insulin. Hyperinsulinemia stimulates cytochrome p450 enzymes in the ovary directly; or indirectly through action of LH or IGF-1, causing hyperandrogenism.[11,12]

Signs of PCOS

• Dermatological issues: Increased androgen levels are sometimes linked to dermatological issues. These include hirsutism (coarse, black hair on the face, belly, chest, and back), acne, and balding/alopecia. Teenage skin issues are frequently attributable to puberty, not PCOS.[13,14]

• Menstrual disorders: Menstrual abnormalities can range in severity from the complete absence of menstruation (amenorrhea) to menstruation that is delayed by 35 days or more (oligomenorrhea) to profuse bleeding (menorrhagia). Women who experience irregular menstrual cycles have a 91% risk of developing PCOS. In addition, PCOS patients are 15 times more likely to report infertility than non-PCOS patients.[15,16]

• Polycystic ovaries: In a single transvaginal ultrasound image, excessive follicles, defined as 25 or more follicles measuring 2 mm to 10 mm, may be seen in PCOS. Additionally, increased ovarian volume, defined as an ovary larger than 10 mL, is also an attribute. Women with PCOS are at risk for developing type 2 diabetes and cardiovascular disease. They are also at a threefold greater risk of developing uterine cancer.[15] In addition, women with PCOS are at higher risk for mental health disorders—such as anxiety and depression. Because of the severe effects of PCOS on many aspects of health, collaborative research efforts will be essential for advancing diagnosis and treatments and reducing the suffering of women with this disorder.[17]

Risk Factors for Developing PCOS

• Genetics: A recent study documented that pregnant woman with PCOS exhibit increased circulating AMH levels compared with control women. Thus, girls born from mothers with PCOS might be at a greater risk of developing this endocrine disorder not only due to the abnormal exposure to androgens during gestation, but also due to the intrauterine AMH excess. Low birth weight due to intrauterine growth restriction is also thought to be a contributing factor for the development of PCOS. Along the same lines, it has been shown that the prevalence of symptoms of PCOS is higher in young adult women born small for gestational age compared to women born with adequate body weight at birth. Such women exhibit altered insulin sensitivity, increased androgenic activity, and irregular menses. These findings suggest that changes in the intrauterine nutritional environment may also be considered a significant factor for the development of PCOS.[18,19]

• Diet: Diet has also been found to be a contributing factor for PCOS. Dietary fats and proteins can form advanced glycation end products (AGEs) when exposed to sugar in the bloodstream.[20] AGEs are known to contribute to increased bodily stress and inflammation, which have been linked to diabetes and cardiovascular disease. Since PCOS patients already have an increased likelihood for metabolic syndrome, cardiovascular issues, and diabetes it is best to limit exposure to AGEs in these individuals. Animal-derived foods that are high in fat and protein are generally AGE-rich and prone to more AGE formation during cooking.[21]

• Lifestyle: Obesity is a common exacerbating factor for PCOS. Therefore, maintaining a healthy weight is strongly advised. Exercise can alleviate many PCOS symptoms, including depression, inflammation, and excess weight gain. Women with PCOS should be advised to restrict inflammatory foods, such as milk products, gluten foods, and highly glycemic foods such as potatoes, white bread or sucrose desserts.[22]

• Environmental Exposure Risks: According to research, the greatest risk from endocrine disrupting chemicals occurs during prenatal and early postnatal development, when organ systems are developing. Many of the things we use daily include endocrine disruptive chemicals, including some plastic bottles and containers, liners for metal food cans, detergents, flame retardants, food, toys, cosmetics, and pesticides. Reproductive health may benefit from limiting personal exposure to endocrine disrupting substances.[23]

Therapeutic Options for PCOS

• Antiandrogens: To achieve satisfactory results against acne and hirsutism, an OCP regimen of at least 6 months is usually required. When this treatment is no longer effective, additional therapies may be employed.[24]

• Spironolactone: Hirsutism is effectively treated with spironolactone. There is also inconclusive evidence on its efficacy. It has the effects of a diuretic and an antagonist of aldosterone; it binds to androgen receptors and blocks the actions of androgens. Other mechanisms include inhibition of ovarian and adrenal steroidogenesis, competition for androgen receptors in hair follicles, and inhibition of 5-reductase activity.[25]

• Flutamide: Another nonsteroidal anti-androgen that has been demonstrated to be beneficial against hirsutism in smaller trials is flutamide, an androgen-receptor agonist. Dry skin is the most prevalent adverse effect, but hepatitis is a possible side effect in very rare situations. There is a substantial risk of teratogenicity, and women should utilize contraception. Combining lifestyle and metformin therapy with flutamide has also been shown to help women with PCOS.[26]

• Finasteride: The enzyme 5-reductase is inhibited by finasteride (type 1, predominantly found in the skin, and type II, predominantly found in the prostate and reproductive tissues). Compared to other anti-androgens, finasteride has less hepatic and renal toxicity, but it is associated with teratogenicity in male fetuses. Adequate contraception should be used to avoid a fetus being exposed to finasteride. Randomized trials have found that spironolactone, flutamide, and finasteride have equivalent efficacy in the treatment of hirsutism.[27]

• Inhibitors of ornithine decarboxylase: These are intended for the treatment of hirsutism in women. Ornithine decarboxylase is also an indicator of androgen action in the prostate and the key enzyme in the synthesis of polyamines. Cell division and function in the pilosebaceous unit are dependent on this enzyme being inhibited. Eflornithine (brand name Vaniqa) Is an efficient new topical therapy for unsightly facial hair has just been discovered.[28]

• Statins: Statins can also be employed to help women with PCOS with a cardiovascular and endocrine advantage. Hyperandrogenemia, lipid concentrations and inflammation have been proven to be improved. However, its long-term effects are uncertain in young women with PCOS in the prevention of cardiovascular diseases. There is some concern with the use of this medicine in reproductive women due to teratogenicity. In women with PCOS, the use of these medicines is still experimental.[29]

• Sensitizing agents for insulin: In the long-term maintenance of PCOS, metformin is the primary insulin-sensitizing drug. Metformin reduces androgens in serum and enhances the frequency of ovulation and menses. Because of its positive, safe profile and familiarity in a wide variety of caregivers from other fields of medication, metformin tends to be the medicine of choice to treat glucose intolerance and increased diabetes risk in women with PCOS. However, no long-term metformin studies are available in PCOS women for the prevention of diabetes. Glucose tolerance improves or stays stable over time among women with PCOS who use metformin. In combination with lifestyle therapy, PCOS is commonly treated with metformin.[30]The most common adverse events are the gastrointestinal symptoms (diarrhea, nausea, vomiting, abdominal bloating, flatulence and anorexia). The dose usually amounts to 1500-2000 mg/day at divided doses. Since the administration of metformin and statins has various adverse effects, such as nausea, vomiting, gastric discomfort, combined treatment with natural products, such as monacolin k, inositol’s, lipoic acid, glucomannan, and bergamot, represents a valid alternative that is well tolerated and with a similar mode of action.
  Since the administration of metformin and statins has various adverse effects, such as nausea, vomiting, gastric discomfort, combined treatment with natural products, such as monacolin k, inositol’s, lipoic acid, glucomannan, and bergamot, represents a valid alternative that is well tolerated and with a similar mode of action.

• Inositol: The 9-inositol stereo isomer family contains myo-, cis-, allo-, epi-, mucosa-, neo- and scyllo- and chiro-inositol’s optical isomers D and L. The most used in nature is myo-inositol (MI). In general, MI supplementation has been shown to improve numerous PCOS hormonal abnormalities. MI action mechanisms appear mainly to positively affect the reproductive axis (MI stores ovulation and improves oocyte quality) and hormonal functions (Mi reduces clinical and biopsychic hyperandrogenism and dyslipidemia) by reducing insulin plasma levels. In recent years, the scientific interest in the discovery of novel natural alternatives for the treatment of PCOS symptoms has been the lack of side effects with the administration of these products.[32]Inositol and monacolin, inositol and lipoid acid, and inositol and bergamot are all viable connections. These novel combinations may work against the etiologies underlying the onset and progression of PCOS-related symptoms. Furthermore, these natural alternatives are more readily accepted by patients and clinicians who view metformin as an only anti-diabetic medication and any other uses as “off-label”.

Prevalence of Women with PCOS

As stated above, PCOS is the most frequent endocrine condition in premenopausal women. The global prevalence of this illness ranges from 6% to 20% depending on the diagnostic criteria used, with a higher prevalence among overweight or obese women and particular ethnic groups.[1,3]

At least 70% of women with PCOS do not receive a diagnosis in primary care. Some health care providers are less knowledgeable about the numerous PCOS diagnostic criteria and phenotypes. Increased awareness of PCOS (and its causes and symptoms) may aid in diagnosis and subsequent management. Researchers at Monash University in Australia have produced international evidence-based guidelines for assessing and managing PCOS to assist patients and healthcare providers. They fully embrace the Rotterdam PCOS diagnostic criteria for adults, which serve as the standard for medical practitioners diagnosing PCOS.

Where Treatment Areas Are Lacking for PCOS Patients

There is minimal research on multidisciplinary PCOS clinics and their treatment success. It is generally known that PCOS is a complex syndrome with a wide range of symptoms. When treating a PCOS patient, it is critical to address immediate demands while reducing long-term risks. Symptoms will be best treated if a team of professionals works together. Individuals exposed to several physicians are less likely to miss a PCOS diagnosis. The earlier PCOS is diagnosed and treated, the better the quality of life and prognosis. Globally, multidisciplinary clinics are regarded to promote patient satisfaction, weight loss, body image, and holistic PCOS management. It is crucial to note that some of the research we have highlighted about innovative compounded products for PCOS is preliminary and was conducted on a small population; higher sample sizes will also help to boost future studies.[33]

Common Medications Used for PCOS That Can Be Compounded

The following drugs are available to compound into unique dosage forms to help PCOS patients.

Inositol and Monacolin K: Red yeast rice, a Chinese dietary supplement, has recently acquired prominence due to its natural statin qualities. It contains various concentrations of natural monacolin K (mevinolin), a metabolite of Monascus rubber that inhibits 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase, the rate-limiting enzyme in the Monacolin K was proposed to have a comparable effect on lipid metabolism as pharmaceutical statins, and it was proven to effectively lower cholesterol levels in patients with hypercholesterolemia. Additionally, it was claimed that its ability to inhibit steroid synthesis was responsible for the observed decrease in hyperandrogenism, which may restore ovulation in those with PCOS, as was previously demonstrated following the use of simvastatin alone or in combination with metformin. Furthermore, statins and monacolin K’s antioxidative characteristics may help to further limit cellular proliferation and improve ovulatory function.38,39,40

Inositol and Lipoic Acid: A very strong antioxidant, alpha lipoic acid, was demonstrated to improve glucose management in type 2 diabetic patients and improve sensitivity to insulin and reproductive and metabolic abnormalities in women with PCOS. Recently, scientists have shown that alpha lipoic acid with inositol can be used as a dietary supplement for improving insulin-resistant sensitivity.[33] 

Glucomannan and Inositol: Glucomannan is a water-soluble, fermentable dietary fiber derived from the elephant yam tuber or root, often known as konjac (Amorphophallus konjac or Amorphophallus rivieri). Because of its large molecular weight and ability to absorb up to 50 times its weight in water, it is one of the most viscous dietary fibers known. Glucomannan appears to assist weight reduction by displacing the energy of other nutrients and generating satiety as it absorbs water and expands in the gastrointestinal tract due to its low energy density and bulking properties. Furthermore, glucomannan appears to lower total cholesterol and low-density lipoprotein (LDL) cholesterol levels by increasing fecal excretion of cholesterol and bile acids and lowering intestinal cholesterol absorption. Furthermore, because of its increased viscosity, glucomannan may enhance glycemic indices by suppressing hunger and decreasing intestine absorption.[33]

Inositol and Bergamot: Pharmacological investigations have validated the effects of bergamot juice that were previously known in folk medicine, such as its cholesterol-lowering and lipid-lowering properties. The flavonoids are primarily responsible for these effects. Clinical research has revealed that the activity of individual flavonoid compounds does not have the same potency as the full plant complex. The association between inositol, monacolin k, vitamin K2, methyl folate, and bergamot juice has been recently studied for its important action on dyslipidemia.

The relationship between d-chiro-inositol, monacolin-K, bergamot extract, methyl folate, and vitamin K2 is not restricted to lowering total cholesterol but may also increase HDL. The synergistic impact of this new supplement’s nutritional components and plant extracts was shown to effectively restore the altered functional states of the glucolipid metabolism and vascular system.[33]

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Medical Disclaimer This content is for informational and educational purposes only. It is not intended to provide medical advice or take the place of such information or treatment from a personal physician. All readers/viewers of this content are advised to consult their doctors or qualified health professionals regarding specific health questions. Neither Innovation Compounding, Inc. nor the publisher of this content takes responsibility for possible health consequences of any person or persons reading or following the information in this educational content. All viewers of this content, especially those taking prescription or over-the-counter medications, should consult their physicians before beginning any medication, nutritional supplement, diet, or health regimen. Innovation Compounding does not make or intend to make any claims to efficacy or safety of compounded products for specific conditions or disease states, as compounded products are not FDA-approved for these conditions. 

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