Fertility Mapping: Navigating Fertility with PCOS and Insulin Resistance Part II

PCOS is a multifactorial condition impacted by alterations in receptors, metabolism and functionality of hormones, neurotransmitters and nutrients. It is a lifelong condition that contributes to infertility, weight gain, cardiometabolic symptoms and diseases. In this blog, we look at laboratory testing and what can and should be tested in all women where you suspect PCOS.  

Lab Testing for PCOS 

Polycystic ovarian syndrome (PCOS) diagnosed through the Rotterdam criteria, a comprehensive framework that encompasses a variety of indicators, including clinical symptoms, laboratory findings of elevated testosterone levels, ovulatory dysfunction, and ultrasound evidence of ovarian cysts. Women do not have all the criteria to be diagnosed. In general, PCOS is a clinical diagnosis. For further details on the Rotterdam criteria please refer to the following resource: NCBI Article. 

Recommended lab testing: 

  • Women with PCOS are recommended to test the following hormones 
  • 17 OH Progesterone – rule out congenital adrenal hyperplasia  
  • Cortisol – rule out Cushing's syndrome 
  • DHEAS 
  • Glucose  
  • Hgb A1c  
  • hsCRP 
  • Insulin  
  • LH/FSH on day 3 or 4 of the cycle (during the period) is usually 1:1 but can be 2:1 or higher. 
  • Lipids/Cholesterol  
  • Prolactin – high prolactin can also stimulate irregular periods and polycystic ovaries 
  • SHBG – if doing total hormone levels. 
  • Testosterone  
  • TSH 

In both saliva and bloodspot testing, it is common to observe elevated levels of testosterone and DHEAS, alongside reduced progesterone levels. Although women with PCOS may exhibit symptoms of estrogen dominance, estrogen levels are rarely high. Results from salivary laboratory assessments typically look like this although this patients DHEAS is not elevated. 

Due to the tight ranges measuring bio-available testosterone and DHEAS utilized in saliva testing, elevated testosterone levels are often more clearly identified in saliva testing as compared to serum testing.

In this individual you can see that the total testosterone in bloodspot is at the top of the normal range, but the insulin is very high in this fasting sample. The optimal fasting insulin should be less than 10. Although not reported, this individual’s hemoglobin A1c was optimal. 

Similarly, in urine analysis, indications of PCOS may include heightened levels of testosterone, androstenedione, DHEA, and DHT. A profile suggestive of PCOS is shown below. Notice the very high DHT as well as the other androgens.  

Treatment of PCOS 

The first goal for PCOS is to lower insulin levels which then decreases androgen levels and increases progesterone levels via ovulation. Ideally women will have 6 months of health optimization before attempting pregnancy and especially if utilizing assisted reproduction therapies.  However, if discontinuing oral contraceptives conception should be attempted the first month after stopping contraceptives. 

Insulin Reduction 

Interventions encouraging lower simple carbohydrates, increasing complex carbohydrates, and increasing dietary fiber should be a basis for all women with PCOS. Medications like metformin and GLP1s, herbs like Berberine, and nutrients like inositol should be considered in women with higher insulin levels even in with normal body weight.  

Inositol, otherwise known as vitamin B8, is a sugar that the body uses in receptor functionality. Inositol also acts as a secondary insulin messaging, therefore reducing insulin resistance. Its action on cellular receptors is not limited to insulin but is involved in the neurotransmitters and all hormones. In women with PCOS, inositol fails to be recycled in the cells and is overall deficient (1). Inositol supplementation has been shown to decrease insulin and glucose, improve menstrual cycles and has improved pregnancy rates. Inositol levels are high in ovum follicular fluid and ovum with higher levels of inositol are associated with higher quality.  

Other therapies such as melatonin and vitamin D may be appropriate for many patients. Usage of some of these supplements and medications throughout pregnancy for women with PCOS especially metformin and inositol suggest that optimizing insulin may lead to better pregnancy outcomes (2, 3).  

Achieving pregnancy with PCOS may require additional effort. Diligently managing insulin levels and optimizing weight and overall health significantly contribute to success of conception, even when assisted reproductive technologies may be necessary. Incorporating lifestyle optimization into treatment plans for preconception, conception, pregnancy, and postpartum care is essential for nurturing the healthiest eggs, embryos, and babies. ZRT extends heartfelt wishes for success to all. 

References:

  1. Greff, Dorina, Juhász, Anna, Váncsa, Szilárd, Váradi, Alex, Sipos, Zoltán, Szinte, Julia, Park, Sunjune, Hegyi, Péter, Nyirády, Péter, Ács, Nándor, Várbíró, Szabolcs, Horváth, Eszter. "Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials." NIH. PubMed, Jan. 26, 2023, https://pubmed.ncbi.nlm.nih.gov/36703143/. 
  2. Laganà, Antonio Simone, Myers, Samuel H, Forte, Gianpiero, Naem, Antoine, Krentel, Harald, Allahgoli, Leila, Alkatout, Ibrahim, Unfer, Vittorio. "Inositols in treating polycystic ovary syndrome and non-insulin dependent diabetes mellitus: now and the future." NIH. PubMed, Jan. 22, 2024, https://pubmed.ncbi.nih.gov/38226638/.
  3. Dodd, Jodie M., Grivell, Rosalie M., Deussen, Andrea R., Hague, William M. "Metformin for women who are overweight or obese during pregnancy for improving maternal and infant outcomes." NIH. PubMed, Jul. 24, 2018, https://pubmed.ncbi.nih.gov/30039871/.