The Polycystic Ovary Morphology-Polycystic Ovary Syndrome Spectrum

Abstract

Background: Polycystic ovary syndrome (PCOS) is the most common cause of chronic hyperandrogenic anovulation. Two-thirds of PCOS patients have functionally typical PCOS, with typical functional ovarian hyperandrogenism manifest as 17-hydroxyprogesterone hyper-responsiveness to gonadotropin stimulation. Most, but not all, of the remainder have atypical functional ovarian hyperandrogenism. Many asymptomatic volunteers with polycystic ovary morphology (PCOM) have similar abnormalities.

Objective: The objective of this paper is to review the relationship of biochemical ovarian function to the clinical spectrum observed in PCOS and in normal volunteers with PCOM.

Findings: Adolescents and adults with PCOS are similar clinically and biochemically. Ninety-five percent of functionally typical PCOS have classic PCOS, ie, hyperandrogenic anovulation with PCOM. In addition to having more severe hyperandrogenism and a greater prevalence of PCOM than other PCOS, they have a significantly greater prevalence of glucose intolerance although insulin resistance is similarly reduced. Half of normal-variant PCOM have PCOS-related steroidogenic dysfunction, which suggests a PCOS carrier state.

Conclusions: There is a spectrum of ovarian androgenic dysfunction that ranges from subclinical hyperandrogenemia in some normal-variant PCOM to severe ovarian hyperandrogenism in most classic PCOS. A minority of mild PCOS cases do not fall on this spectrum of ovarian androgenic dysfunction, but rather seem to have obesity as the basis of their hyperandrogenism, or, less often, isolated adrenal androgenic dysfunction. Half of normal-variant PCOM also do not fall on the PCOS spectrum, and some of these seem to have excessive folliculogenesis as a variant that may confer mild prolongation of the reproductive lifespan. Improved understanding of PCOM in young women is needed.

Keywords: Glucose intolerance; Insulin resistance; Obesity; Polycystic ovary; Polycystic ovary syndrome.

Fig. 1

The spectrum of ovarian androgenic function from normal to functionally typical PCOS. The position of study groups and subgroups along the spectrum is indicated schematically in relation to evidence of ovarian dysfunction. Study groups and subgroups as defined in the text: V-NOM (volunteers with ultrasonographically normal ovarian morphology), V-PCOM (volunteers with polycystic ovarian morphology, PCO), PCOS-A (functionally atypical PCOS), PCOS-T (functionally typical PCOS). Defining abnormality of group or subgroup: +, abnormal, −, normal. Experimental findings shown as % abnormal.^, *, some normal volunteers had impaired glucose tolerance. GnRH, gonadotropin releasing hormone; Dex, dexamethasone; supp, suppression. Modified with permission from Rosenfield et al: Antimüllerian hormone levels are independently related to ovarian hyperandrogenism and polycystic ovaries. Fertil Steril 2012; 98:242.

Fig. 2

Scatterplots demonstrating relationships among tests for ovarian hyperandrogenism, polycystic ovarian morphology (PCOM), and serum AMH concentrations. Subjects are healthy eumenorrheic non-hirsute volunteers with normal or polycystic ovarian morphology (n = 21 V-NOM, n = 32 V-PCOM) and patients with PCOS identified by NIH criteria (n = 20 PCOS-A, n = 40 PCOS-T). This figure is an alternative display of published data in age-matched 11.1–39.9 year olds.^– Encircled PCOS cases have PCOM. Serum for AMH was available in 90% of subjects with tests of ovarian androgenic function. Dotted lines show the 95^th percentile of normal for the V-NOM reference group; thus (a) quadrants show normal ranges. A, The relationship between the results of the short dexamethasone androgen-suppression test (SDAST) and the GnRHag test of androgenic ovarian function (r = 0.671, P < .0001) divides PCOS into 3 subgroups. Functionally typical PCOS (PCOS-T) is defined by an elevated 17OHP response to the GnRHag test (c). Functionally atypical PCOS (PCOS-A) lacks 17OHP elevation in response to GnRHag: DAST indicates that 60% of these PCOS-A cases have atypical FOH (b) and 40% of PCOS-A cases have normal ovarian androgenic function (a). B, SDAST relationship to baseline AMH levels. C, Twenty-two percent (n = 7) of healthy volunteers with PCOM have “hyperandrogenic PCOM” (V-PCOMh), defined as occult baseline hyperandrogenemia with FOH, as indicated by an abnormal SDAST or GnRHag test (b–d). Adolescent V-PCOM tended to have FOH less often (1/9) than adult V-PCOM (6/23). “Dysregulated” PCOM (V-PCOMd) is delineated by an abnormal 17OHP response to GnRHag in the absence of baseline hyperandrogenemia (d). This figure corrects a data entry error in the original publication that misclassified a V-PCOMd as V-PCOMh. D, AMH elevation of a similar extent is found in normoandrogenic and hyperandrogenic normal volunteers who have PCOM. Adapted with permission from Rosenfield et al: Determination of the source of androgen excess in functionally atypical polycystic ovary syndrome by a short dexamethasone androgen-suppression test and a low-dose ACTH test. Hum Reprod 2011; 26:3138, and Rosenfield RL, et al: Antimüllerian hormone levels are independently related to ovarian hyperandrogenism and polycystic ovaries. Fertil Steril 2012; 98:242.

Fig. 3

Schematic representation of the spectrum of ovarian function found in eumenorrheic non-hirsute healthy volunteers with PCOM (normal-variant PCOM, V-PCOM) in relation to the spectrum between normal and PCOS.^, Forty percent of V-PCOM have ovarian function like that of similar volunteers who lack PCOM. Another 10% of V-PCOM has elevated AMH in the absence of any evidence of ovarian steroidogenic dysfunction, which suggests an isolated increase in folliculogenesis. The remaining half of V-PCOM has some degree of PCOS-related steroidogenic dysregulation, often with mild AMH elevation (see Figs. 1, 2). Of those with ovarian steroidogenic dysfunction, nearly half (22% of the V-PCOM group) have biochemically hyperandrogenic PCOM, ie, subclinical FOH that meets the definition of “ovulatory PCOS.” The remainder have isolated dysregulation of ovarian function (ie, 17OHP hyper-responsiveness to GnRHag testing in the absence of hyperandrogenemia).