Treatment

Let’s look at the major drivers of the condition: Genetics teaches us that in PCOS there are genetic polymorphisms at a pituitary level (gonadotrophin releasing hormone receptor (GnRHR) and at an ovarian level follicle stimulating hormone receptor(FSHR), Steroidogenic acute regulator gene (StAR), which is the starting point of hormone synthesis. The StAR gene encodes StAR gene product (the StAR protein), which regulates the transport of cholesterol through the mitochondrial membrane in the first step of androgen biosynthesis. increased production or concentration of StAR may be responsible for the increased ovarian and adrenal androgen found in PCOS of some patients.

There are also a number of insulin receptor (IR) /insulin receptor substrate (IRS) and other metabolic gene single nucleotide polymorphisms (SNPs) have been found in the fat mass and obesity-associated (FTO) gene, the methylene tetrahydrofolate reductase (MTHFR) gene, the peroxisome proliferator activated receptor gamma (PPARG) the gene product PPAR-γ plays an important part in the management of energy storage and insulin sensitivity.

Other gene polymorphisms include the vitamin D receptor gene (VDR) the gene product of which not only affects bone metabolism but can also affect insulin sensitivity and appears involved in PCOS insulin resistance.

Immunological gene SNPs in PCOS include lnterleukin 1 beta (IL-1b). and interleukin 1 receptor antagonist (IL-1RA) (Chen 2018). PCOS is a pro-inflammatory condition and many pro-inflammatory immune mediators have been found including excessive cytokines. Interestingly, IL-1β has also been reported as a crucial moderating element in ovulation, fertilization, embryo implantation and tissue restructuring Another important member of the IL-1 family is IL-1RA; which is able to minimize the inflammatory response. However, polymorphisms of these gene result in dysfunctional proteins poor ovarian function and heightened inflammation.

From the above it can be seen that there are hormonal, metabolic and immunological gene SNPs which encode proteins which are dysfunctional in their actions and which are all part of this complex condition involving hormonal, metabolic, immunological, inflammatory and oxidative events., resulting in ovulatory failure, follicle ‘stuck’ in an undeveloped phase unable to reach maturity and are not selected for ovulation, hyperproduction of androgens and oestrogens, weight gain, insulin resistance and the onward march to Metabolic Syndrome, Type 2 Diabetes and cardiovascular disease. The high androgens and oestrogens keep the hormonal and metabolic dysfunction ‘on track’, but hyperoestrogenemia also has more sinister complications potentially for PCOS sufferers, that being an increased risk of endometrial cancer.

Hence there are a multitude of treatment opportunities to aim to bring some degree of balance and functional organization to effect better ovarian function through multiple mechanisms, as well as improvement of hormone levels which ease up on perpetuating the cycle of hypothalamic, pituitary and ovarian hormone imbalance.

PCOS SUPPORT Metabolic Balance, uses a unique group of herbal and mineral ingredients. Gynostemma pentaphyllum also known by its traditional name Jiaogulan or Southern Ginseng is indigenous to South East Asia. It has been drunk as a tea for centuries and is known as the Herb of Immortality as it is reputed to prolong life.

Gynostemma has been found to sensitise the insulin receptor, lower insulin resistance through raising AMPK which lowers glucose secretion from the liver. It lowers blood glucose and lowers the long term marker of blood glucose HbA1C better than Glucophage. In a 2012 research article by Hirst et al, maximum HbA1C reduction with Glucophage was 1.1% units. However, a study on Gynostemma found a 2% unit drop in HbA1C (Vu Thi Thanh Huyen 2011).

Chromium has similar insulin sensitizing properties lowering blood insulin and glucose levels.

Chromium facilitates insulin signaling at many points of the insulin signaling cascade. When insulin ‘docks with the insulin receptor, it binds to a part called the alpha subunit. For signal transduction to occur, the beta subunit needs to be activated. Chromium activates the beta sub-unit which in turn phosphorylates (activates) the insulin receptor substrate (IRS) molecules. At this stage chromium stops the breakdown (ubiquination) of IRS-1. Chromium also blocks a molecule which inhibits insulin signally called PTP 1B (protein tyrosine phosphatase 1B). Chromium also promotes other ‘downstream’ signaling molecules like P-I-3-kinase(PI3K) and the Akt. (Hua 2012).

Chromium supports AMPK (5’adenosine monophosphate activated protein kinase) which helps GLUT4 vesicles translocate from inside the cell to the cell surface.

Chromium is a very’ talented’ team player in combatting insulin resistance (IR) and the consequences of IR being glucose intolerance and a higher risk of type 2 diabetes. High blood sugar results in the oxidative damage of proteins (glycosylation or glycation). Chromium is also has antioxidant functions lowering glycosylation of proteins and lowering oxidation of fats (lipid peroxidation).

Chromium boosts glutathione and glutathione peroxidase (premium antioxidants in the body’s antioxidant armory.

Furthermore, chromium is effective in reducing food cravings which of itself could increase weight.

Inositol is a member of the B group of vitamins There are 9 stereoisomers (forms) of inositol. The molecular formula of inositol is identical to that of sugar (C6H12O6) however the 3 dimensional arrangement of the atoms and attachments are different to sugar. It is a sugar alcohol and when taken as a supplement lowers blood sugar levels. Myo-Inositol (MI) is most abundant of all inositols and high amounts are required for oocyte maturation. A German study of 3602 PCOS patients given MI for 3 months restored ovulation in 70% of patients and had a fertility rate equivalent to or better than reported for Glucophage.

How can Myo-inositol be so effective?

Approximately 99% of all inositols is MI and is used interchangeably with inositol. Small amounts of MI are metabolized to D-chiro-Inositol (DCI) by the enzyme epimerase. DCI maintains insulin sensitivity. In PCOS urinary DCI levels are very low. The worse the insulin resistance the lower the DCI in urine of PCOS patients.

Studies have reported improved oocyte function, the start of regular periods after just 34 days treatment with 2grams MI daily. In one study 10 out of 22 women fell achieved biochemical pregnant within 6 months. Another study of 50 PCOS with 2g MI reported lowered LH, lowered LH/FSH ratio, prolactin, androstenedione and insulin. MI resulted in larger quality oocytes and higher pregnancy rates, with 10/50 women falling pregnant and 8 successful deliveries compared to 3 deliveries in non MI treated patients

It has been suggested that MI and DCI reduce insulin resistance, improve ovarian function and reduce androgen levels in women with PCOS.

DCI as a sole agent has also been used. 600mg DCI daily decreased insulin and testosterone levels. Even a higher dose of DCI 500mg bd improved the quality of oocytes.

Supplemental DCI bypasses defective epimerase activity and achieves downstream metabolic effects of insulin in DCI deficient tissues. However in nature epimerase is unidirectional meaning giving DCI cannot fulfil any of the functions of MI. Hence a physiological combination of both Mi is able to enhance oocyte maturation and small amounts of DCI are available with needing epimerase for insulin sensitivity and hormone regulation. Research suggests that lower doses of MI may suffice if co-administered with DCI.In arandomised controlled study of MI/DI versus Mi alone showed a better ovulation, endocrine, metabolic  with better insulin sensitivity and lipid profiles than MI alone (Minozzi 2013)

The formulation of PCOS SUPPORT Hormone Balance was developed out of a clinical recognition that PCOS women suffer symptoms of hyperoestrogenism which having low progesterone as a consequence of hypothalamic, pituitary and ovarian dysfunction. Inflammation is interwoven into the fabric of PCOS likely due to immune gene polymorphisms but also epigenetic effects.

The formula is Calcium-D-Glucarate, Chaste Tree, Cyperus rontundus and Curcumin (95% curcuminoids)

Hyperoestrogenemia can via second messenger effects suppress FSH, and thereby prevent immature follicles I from reaching individual dominance and growth to a mature egg, perpetuating the poor ovulation. Hyperoestrogenemia also induces auto-immunity, which aggravates weight gain, glucose intolerance and immune dysfunction affect thyroid function, slowing metabolism further with concomitant weight gain.

Women with PCOS often have a range of emotional symptoms- anxiety and depression are common. Clinical proven oestrogen metabolizing nutritional treatments improve mood, help PCOS sufferers who have fluid retention lose fluid, lessen headache and mastalgia and sleep better. Lowering oestrogen may have indirect beneficial effects of the ovaries via negative feedback through the hypothalamus and pituitary. Both cyperus and Calcium-D-Glucarate working through different mechanisms may lower oestrogens. Chaste Tree or Chaste berry has been shown to improve progesterone levels in the blood and female genital tract. Chaste Tree improves dopamine and has been shown to lower prolactin level almost as effectively as the standard drug treatment for hyperprolactinemia, bromocriptine.

Often overlooked in PCOS management is the inflammatory effects of genetic driven immune dysfunction. Where we can change the genes, we can modulate inflammation. Curcumin, is a ‘one stop shop’, being a potent anti-inflammatory similar in its effect to non-steroidal anti-inflammatory drugs (NSAIDs) but without the gastric and duodenal sideeffects of NSAIDs.  Curcumin blocks the COX and LOX pro-inflammatory enzymes but also lowers excessive pro-inflammatory cytokines which are released from fat cells which drive the inflammatory response. PCOS patients suffer inflammatory overdrive from immune system genetic polymorphisms (IL-1b and IL_1RA), but also being overweight or obese have increased inflammatory cytokines released from fat cells. Curcumin has been found to lower TNFalpha, IL-1Beta which may be raised in PCOS interleukin 6 (IL-6). TGFb, MCP-1. It also lower NFKB a potent nuclear inflammatory generator. It lowers C reactive protein (CRP).

However, its anti-inflammatory also to reduces Metabolic Syndrome. Curcumin improves insulin sensitivity suppressing fat deposition triglycerides and cholesterol and elevates good cholesterol (HDL).

Curcumin is also a powerful antioxidant lowering reactive oxygen species (ROS), nitrosative stress, malondialdehyde (MDA) a marker of lipid oxidation while supporting ‘on board ‘ antioxidant defense (glutathione, catalase and superoxide dismutase (SOD) (Hawlings 2017)

Vitamin D is actually a hormone not a vitamin at all. It is anti-inflammatory, immune supportive, bone enhancing, muscle supporting. Genetic polymorphisms of the vitamin D receptor, are a component of PCOS metabolic and hormone dysfunction has been shown to play a role in insulin resistance and egg development. Getting some safe sun (early mornings or late afternoons is a great way to get your daily dose. Check your 25 hydroxy vitamin D (25-OH Vit D) level and aim for an optimal high normal reference range level.

Prevent xenoestrogen (toxic environmental oestrogens) exposure by avoiding fumes off all descriptions (car exhaust fumes, cleaning fumes, ‘Braai’ fumes, cigarette fumes, nail polish fumes, nail polish remover fumes, cleaning products, sprays, hair products.These and other polycyclic aromatic hydrocarbon fumes and chemicals  have a potent oestrogenic effect and are potentially precarcinogenic.

Have a religious exercise program with both aerobic and anaerobic components. Exercise lower glucose levels, insulin levels, burns fat mass, improves AMPK.

To maximize the benefits of exercise also participate in a ketogenic diet with most of your eating between 10am and 6pm. Periodic fasting for 16-18hours also improves insulin sensitivity and drives up AMPK.