Evaluating the Pg/E2 Ratio for Estrogen Dominance: What we do and don’t know

The progesterone to estradiol (Pg/E2) ratio was a tool created to assess hormonal imbalance – most specifically estrogen dominance. Estrogen dominance is a term coined by Dr. John Lee, MD in his book Natural Progesterone – The Multiple Roles of a Remarkable Hormone (1993). Here, he describes the importance of progesterone in balancing the effects of estrogen in the body. He explains that women may have estrogen-dominant symptoms even if estrogen levels are normal or deficient because there may not be adequate levels of progesterone to balance estrogen. 

A Helpful Tool for Providers, but More Research is Needed 

The use of Pg/E2 ratio to assess for hormonal imbalance and related symptoms has not been well researched. The majority of research on the Pg/E2 ratio has centered on its utility in predicting success prior to in vitro fertilization (IVF) procedures. The research in this area has found mixed results in the ratio’s significance. Even so, higher estrogen to progesterone levels in the early luteal phase have been found to have favorable outcomes. Even with the lack of research, many practitioners have found the Pg/E2 ratio a helpful tool in clinical practice. 

The Benefits of Assessing the Pg/E2 Ratio 

The Pg/E2 ratio can help determine if there is a healthy balance between progesterone and estrogen when these hormones fall within normal ranges. This is helpful when assessing possible hormone-related symptoms. Although estradiol is not the only estrogen made by the body, it is the most potent and, therefore, most used for this clinical assessment.  

Even if estradiol and progesterone levels are normal, there could still be an imbalance between the two. For instance, a patient could have a relative estrogen dominance where estradiol levels are normal, but they are high relative to progesterone. The Pg/E2 ratio helps to visualize this imbalance. A lower ratio can indicate higher estrogen relative to progesterone, often referred to as estrogen dominance. Conversely, a high ratio can indicate higher progesterone to estrogen (ie. progesterone dominance), potentially leading to hormonal imbalance symptoms. 

Signs and Symptoms of Estrogen Dominance 

The term estrogen dominance is used to describe the hormonal imbalance that occurs when estrogen levels are relatively higher than progesterone levels. With estrogen dominance, there is not enough progesterone to balance the estrogen activity in the body, leading to symptoms associated with unopposed estrogen. Though not as common, there can also be a state of progesterone dominance. Often, elevated progesterone levels in cycling women are normal and do not cause symptoms; however, for some women high progesterone levels can cause symptoms that overlap with symptoms of estrogen dominance.   

High estrogen symptoms include heavy periods, breast tenderness, fibroids, fatigue, brain fog, mood swings, anxiety, bloating, weight gain, and headaches.  Estrogen dominance is typically assessed during the luteal phase (second half of the menstrual cycle), though elevated estrogen levels during the ovulatory phase can also cause estrogen-dominant symptoms.   

Factors that can lead to estrogen dominance include stress, insulin resistance, inflammation, gut health (the estrobolome), obesity, diet, alcohol, estrogen detoxification imbalance, environmental estrogen exposures (xenoestrogens), perimenopause, and puberty. 

Watch my episode on Estrogen Dominance from the Summer School edition of the DUTCH Podcast.  

Signs and Symptoms of Progesterone Dominance 

Though not as common, there can also be a state of progesterone dominance. Often, elevated progesterone levels in cycling women are normal and do not cause symptoms; however, for some women high progesterone levels can cause symptoms that overlap with symptoms of estrogen dominance.  

Symptoms of progesterone dominance include: fatigue, increased appetite, bloating, constipation, breast tenderness, irregular bleeding patterns, low libido, irritability, and premenstrual dysphoric disorder (PMDD). 

Factors that could contribute to progesterone dominance include progesterone or pregnenolone supplementation, pregnancy, low luteal estrogen levels, ovarian cysts, and congenital adrenal hyperplasia. 

Some Caveats to Consider when Assessing the Pg/E2 Ratio 

While the PG/E2 ratio can be helpful in assessing hormonal imbalance, particularly estrogen dominance, there are shortcomings to only focusing on progesterone and estradiol. The ratio does not consider other contributors to excess estrogenic activity, including estrogen metabolites and xenoestrogens.   

The 16-hydroxyestrone metabolite of estrogen is very active at estrogen receptors and can cause tissue proliferation. This estrogenic activity can lead to many high estrogen-related symptoms, including heavy menstrual bleeding, breast tenderness, and fibroid growth. Evaluating estrogen metabolism can give further insights when a patient presents with estrogen excess symptoms. 

Additionally, xenoestrogens, endocrine-disrupting chemicals that mimic estrogens, can also contribute to hormonal imbalance.  These compounds are quite ubiquitous in our modern environment and include plastics, pesticides, and common chemicals found in personal care products, such as parabens and phthalates. 

Measuring the Pg/E2 Ratio 

The Pg/E2 ratio should ideally be analyzed during the middle of the luteal phase of the menstrual cycle when progesterone should be at its peak. Progesterone levels are highest 5-7 days post ovulation. This is typically days 19-22 of a 28-day cycle.  Remember during the follicular/ovulatory phases of the menstrual cycle, progesterone is low and comes mainly from adrenal production. Estrogen is the dominant hormone during these phases and that is normal.  

Conclusion 

When assessing for hormonal imbalance, the Pg/E2 ratio can be a helpful clinical tool. The DUTCH test may help you evaluate for hormonal balance with measurements of all estrogens (estrone, estradiol, and estrone) and progesterone metabolites, including a progesterone serum equivalent. It also gives a detailed analysis of estrogen metabolism, which is overlooked when just focusing on the Pg/E2 ratio. Additionally, a cycle map can be utilized to assess hormonal production and balance throughout the cycle. 

References

Souter I, Hill D, Surrey MW. Midluteal estradiol-to-progesterone ratio 9E2/P4) has no effect on IVF outcome. Fertility and Sterility. 2003;79:23. doi:10.1016/s0015-0282(03)00133-x 

Gruber I, Just A, Birner M, Lösch A. Serum estradiol/progesterone ratio on day of embryo transfer may predict reproductive outcome following controlled ovarian hyperstimulation and in vitro fertilization. J Exp Clin Assist Reprod. 2007;4:1. Published 2007 Mar 19. doi:10.1186/1743-1050-4-1 

Kolan A. Estrogen Dominance. Whole Health Library. July 24, 2018. Accessed November 17, 2023. https://www.va.gov/WHOLEHEALTHLIBRARY/tools/estrogen-dominance.asp 

De Coster S, van Larebeke N. Endocrine-disrupting chemicals: associated disorders and mechanisms of action. J Environ Public Health. 2012;2012:713696. doi:10.1155/2012/713696 

Fishman J, Martucci C. Biological properties of 16 alpha-hydroxyestrone: implications in estrogen physiology and pathophysiology. J Clin Endocrinol Metab. 1980;51(3):611-615. doi:10.1210/jcem-51-3-611