By: Dr. Jonathan Hebert, MD
Editor’s Note: In recognition of PMOS Awareness Month, we are highlighting the important relationship between reproductive and metabolic health. Jonathan Hebert, MD, wrote this article during his fourth year of medical school while participating in the FACTS elective. Dr. Hebert summarized “New Insights in the Diagnostic Potential of Sex Hormone-Binding Globulin (SHBG)—Clinical Approach” by Szybiak-Skora et al., which explored how SHBG may help clinicians better understand the metabolic and endocrine factors associated with PMOS, anovulation, and infertility. Fertility awareness-based methods complement this broader perspective by documenting ovulatory patterns and ovulatory-menstrual-cycle changes that may reveal signs of underlying hormonal or metabolic dysfunction. To learn more about ovarian physiology, be sure to join us for our FACTS virtual conference in November. Early Bird deadline is October 15th, so register today!
In the global initiative to change the name of a medical condition, the former polycystic ovarian syndrome (PCOS) was renamed to polyendocrine metabolic ovarian syndrome (PMOS) on May 16, 2026 through the collaboration of more than 50 patient and professional organizations [1]. The change comes with hopes to refocus public and professional understanding of the disease away from the implication of pathologic ovarian cysts and toward the metabolic and hormonal features truly characteristic of the disease [2]. Growing research has shown that PMOS has systemic features outside of gynecology and obstetrics, including a metabolic component. One potentially useful clinical marker to bridge reproductive and metabolic disease is sex hormone binding globulin (SHBG). In the article “New insights in the diagnostic potential of sex hormone-binding globulin (SHBG)—clinical approach”, Szybiak-Skora et al. expand on the diagnostic potential of SHBG as an often misunderstood lab value associated with obesity, fatty liver, type 2 diabetes mellitus (T2DM), gestational diabetes, infertility, and PMOS [3].
“PMOS has systemic features outside of gynecology and obstetrics, including a metabolic component. One potentially useful clinical marker to bridge reproductive and metabolic disease is sex hormone binding globulin (SHBG).”
SHBG is a glycoprotein produced in the liver that binds to and regulates bioavailable testosterone, dihydrotestosterone (DHT), and estradiol. Some may remember learning that SHBG’s clinical applicability stopped at distinguishing the difference between total and free testosterone. As such, Szybiak-Skora et al. note that most physicians do not appreciate SHBG and its link to hepatic metabolic stress. Low SHBG is associated with hyperinsulinemia. However, the main inhibitory factor of SHBG production appeared to be excess monosaccharide exposure and lipogenesis in experimental models—evidenced by a sharp reduction in SHBG in the presence of glucose and fructose alone. Low SHBG is associated with poor metabolic states, such as metabolic syndrome, obesity, hepatic steatosis, and hypothyroidism. Low SHBG alone is a risk factor for both T2DM and gestational diabetes development. The opposite is true as well, with high SHBG levels associated with protection from T2DM development, a fasting state, weight loss, and euthyroidism.
“Low SHBG is associated with poor metabolic states such as metabolic syndrome, obesity, hepatic steatosis, and hypothyroidism… (and) is a risk factor for both T2DM and gestational diabetes.”
PMOS is the most common endocrine disorder in reproductive age women and has a multisystem pathophysiology, including metabolic and ovarian dysfunction. Unsurprisingly, low SHBG is associated with PMOS and is predictive of the condition.. This makes sense because although low SHBG is not one of the Rotterdam criteria, elevated androgen levels are. Low SHBG naturally increases the free fraction of androgens. This makes it a critical lab value when investigating hyperandrogenism in females. One study found that women with naturally lower levels of SHBG due to the presence of a mutant allele had a greater risk of PMOS. The research indicates the clinical usefulness of this relationship, stating that SHBG levels may become a useful biomarker for the diagnosis of patients suffering with amenorrhea. For example, a patient with functional hypothalamic amenorrhea may also present with polycystic ovarian morphology and be confused for a patient with PMOS according to the Rotterdam criteria. Here, a normal or high SHBG level would help alert a clinician to the absence of metabolic stress. Other useful labs in this category include metabolic markers, such as adiponectin, apelin 12 and 36, and leptin, which have all been found to be correlated with SHBG levels in PMOS.
“Low SHBG naturally increases the free fraction of androgens. This makes it a critical lab value when investigating hyperandrogenism in females.”
One critical aspect of PMOS is anovulation leading to infertility. Interestingly, the relationship between SHBG and infertility has been studied, with one study finding a protective effect of high levels of SHBG on female infertility. The protective effect was specifically tied to a decrease in anovulation and low SHBG levels resulting in larger, unruptured follicles. Other findings include an increased predictive value for conception, pregnancy, and live births. Low SHBG levels and SHBG gene alterations are associated with male infertility as well.
“The relationship between SHBG and infertility has been studied, with one study finding a protective effect of high levels of SHBG on female infertility.”
Szybiak-Skora et al. describe even more clinical relevance of SHBG beyond the scope of this essay in the realms of cardiovascular disease, thyroid disease, and cancer. This research emphasized the strong correlation between ovulatory health and metabolic health. Stress, activity, diet, and even psychology can greatly affect ovulation. Learning the science behind SHBG underscores this further. A holistic approach to PMOS would include attention to the metabolic stress and possible insulin resistance of the patient, which may be further assisted by a SHBG test. Clinicians may consider adding SHBG testing when assessing gestational diabetes and T2DM risk, as well as when working up anovulation and infertility in cases. As the paper states, there is a lack of research on the relationship between female hypogonadism and SHBG. More clinical research is necessary before SHBG could become a routine biomarker for endocrine and metabolic panels.
REFERENCES
[1] Endocrine Society. Polyendocrine Metabolic Ovarian Syndrome: New name to improve diagnosis and care of condition affecting 170 million women worldwide. Endocrine Society. Published May 12, 2026. Accessed May 21, 2026. https://www.endocrine.org/news-and-advocacy/news-room/2026/pcos-name-change
[2] Teede HJ, Bahri Khomami M, Morman R, et al. Polyendocrine metabolic ovarian syndrome, the new name for polycystic ovary syndrome: a multistep global consensus process. The Lancet. 2026; 0
[3] Szybiak-Skora W, Cyna W, Lacka K. New insights in the diagnostic potential of sex hormone-binding globulin (SHBG)—clinical approach. Biomedicines. 2025;13(5):1207.
ABOUT THE AUTHOR
Jonathan Hebert, MD, is a first-year OB/GYN resident training at Sisters of Charity Hospital in Buffalo, NY. He completed his medical degree at University of Texas Rio Grande Valley (UTRGV) School of Medicine in Edinburg, TX. Dr. Hebert enrolled in the FACTS elective to better understand natural family planning methods and how to share them with patients so they can feel more empowered in their health and reproductive decisions.
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