eMedicine Specialties > Radiology > Obstetrics/Gynecology

Polycystic Ovarian Disease (Stein-Leventhal Syndrome)

Author: Greg Marrinan, MD, Staff Physician, Department of Radiology, Bridgeport Hospital
Coauthor(s): Marjorie Stein, MD, Clinical Assistant Professor of Radiology, Albert Einstein College of Medicine; Consulting Staff, Department of Radiology, Montefiore Medical Center
Contributor Information and Disclosures

Updated: Aug 11, 2009

Introduction

Background

In polycystic ovary disease, enlarged ovaries with thickened sclerotic capsules and an abnormally high number of follicles are present. The follicles may concurrently exist in varying states of growth, maturation, or atresia.^{1,2,3,4,5,6,7,8,9}

Although a multiplicity of clinical presentations exists for polycystic ovary disease, in 1935, Stein and Leventhal reported the classic symptomatology in a group of women who had amenorrhea, infertility, hirsutism, and enlarged polycystic ovaries.¹⁰ The authors found that, after ovarian biopsy, the women began to menstruate regularly. As was discovered over time, women may have polycystic ovaries, yet their cases may not conform to all of the original criteria for this condition. Therefore, Stein-Leventhal syndrome became a subgroup of a more encompassing disease called polycystic ovary disease.

As more information regarding the nature of the condition has come to light, other terms have been applied, including polycystic ovarian/ovaries syndrome and polyfollicular ovarian disease. In actuality, polycystic ovaries are not the primary cause of amenorrhea or hirsutism in this condition. Rather, they are simply one sign of an underlying endocrinologic disorder that ultimately results in anovulation.

Recent studies

Shah et al, in a retrospective observational case series, studied polycystic ovary syndrome (PCOS) in 6 premenarcheal adolescents and 6 adults with unexplained ovarian torsion. From the study findings, they proposed that premenarcheal girls presenting with ovarian torsion, without obvious ovarian pathology, be screened for ultrasound and biochemical evidence of PCOS. The authors suggested that in those with evidence of PCOS, treatment with oral contraceptives be considered, taking into account age and pubertal development, to decrease ovarian volume.¹¹

Tracy Bekx et al studied the characteristics of 77 adolescent girls with PCOS (84% white; average age, 16.2 y [range 11-22 y]). Body mass index (BMI) was greater than the 85th percentile in 84%, and 70% had a BMI greater than the 95th percentile. Menstrual pattern was quite varied, with some patients having primary amenorrhea. Over 50% had hirsutism. There were 3 cases of type 2 diabetes, and over 50% of the patients had elevated fasting insulin levels and low high-density lipoprotein (HDL) levels.¹²

Hudecova et al compared the long-term reproductive outcome and ovarian reserve in 91 patients with confirmed PCOS with those of a control group consisting of 87 healthy women. Of the women who had attempted to become pregnant, 86.7% of PCOS patients and 91.6% of control patients had given birth. Of the PCOS patients who had given birth, 73.6% had done so following spontaneous conception. Mean ovarian volume and the number of antral follicles in PCOS patients were significantly greater than those in the control group. In addition, the PCOS patients had higher serum anti-Müllerian hormone concentrations and lower levels of follicle-stimulating hormone. According to the authors, the study showed that PCOS patients have a good fecundity and, possibly, an ovarian reserve that is superior to that in women who have normal ovaries.¹³

For excellent patient education resources, visit eMedicine's Women's Health Center. Also, see eMedicine's patient education articles Ovarian Cysts, Amenorrhea, and Female Sexual Problems.

Pathophysiology

The pathophysiology of polycystic ovarian syndrome is a highly debated and complex topic. A full discussion of the underlying endocrinologic alterations is far beyond the scope of this article; however, a brief discussion of the currently accepted model may suffice.^{14,15,16,17,18,19,20}

In the normal state, the hypothalamus secretes gonadotropin-releasing hormone (GnRH) in a pulsatile manner. The pituitary gland responds to GnRH by releasing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in a similar cycle. In the follicular phase of the menstrual cycle, LH acts primarily on the theca cells of the ovary to increase the production of androgenic precursors. Concurrently, FSH acts on the granulosa cells to promote conversion of the androgens into estrogens, particularly estradiol, which assists in follicular development. During the follicular phase, increasing levels of estradiol lead to an LH surge. In a complex interaction, the LH surge, the elevated levels of estradiol, and an increase in the circulating progesterone level trigger the midcycle surge of FSH.

In polycystic ovarian syndrome, the above cycle is disturbed. Any of several possible precipitating factors may contribute to the imbalance. Evaluation of blood serum levels typically reveals elevated LH levels and normal or low FSH levels. Patients also have increased levels of free estrogen, primarily estrone and estradiol. Estrogens exert a complex feedback effect on the pituitary gland that results in the suppression of FSH secretion and the increased release of LH. Thus, the production and release of androgen precursors by ovarian theca cells is increased. The peripheral conversion of androgens to estrogens, primarily estrone, strengthens the feedback effect on the pituitary gland.

The same androgens also inhibit the production of sex hormone-binding globulin in the liver, indirectly increasing levels of free estrogen in the bloodstream as well. Locally, elevated androgen levels in the ovary exert a direct inhibitory effect on follicular maturation. In conjunction with the diminished but steady presence of FSH, the follicles continue to develop without ever maturing. Thus, numerous follicles are present in the polycystic ovary and show varying phases of development and atresia.

The proposed causes of polycystic ovarian syndrome are numerous and may, in fact, be multiple. They vary from increased androgen production by the adrenal glands at puberty or times of stress to disturbances in the cyclic pattern of GnRH release by the hypothalamus. Several studies have revealed an inherited form of the disease that appears to exhibit autosomal dominant transmission with incomplete penetrance. Clearly, the pathophysiology of this disease is complex, and much remains to be learned about it.

Frequency

International

The prevalence of polycystic ovaries is difficult to accurately quantify. The inclusion criteria of most studies limit participants to those with specific clinical symptoms or syndromes and thus preclude a full accounting. In other studies, control subjects without polycystic ovaries often have symptoms that are associated with polycystic ovarian syndrome. Thus, a dilemma of nomenclature surrounds this clinical entity.

Most authors agree that polycystic ovaries are present in 3-7% of women worldwide. Almost 75% of women with irregular menses and/or infertility may have polycystic ovaries, as determined with both radiologic and biochemical criteria. Polycystic ovaries have been found with ultrasonography in more than 50% of women with regular menstrual cycles as well; however, most of these women had some degree of hirsutism, acne, or male-pattern baldness.

Mortality/Morbidity

• Infertility is the most common clinical finding in patients with polycystic ovarian syndrome. Low levels of circulating FSH and increased androgen production in the ovary prevent follicular maturation and ovulation.
• Endometrial adenocarcinoma has been associated with polycystic ovarian syndrome. Unopposed estrogenic stimulation of the endometrium is known to increase the risk of endometrial hyperplasia and its subsequent transformation into endometrial carcinoma. In addition, the risk of breast cancer may be increased.
• Secondary effects of the elevated levels of circulating androgens include, but are not limited to, hirsutism, abnormal or absent menstrual cycles, virilization, and dysmenorrhea.

Sex

Polycystic ovarian disease occurs only in females.

Age

• Polycystic ovaries can be diagnosed in patients of any age, from menarche through menopause.
• Typically, women in their 20s present with difficulty conceiving.
• Although uncommon, some patients between ages 10 and 20 years present with primary amenorrhea.

Anatomy

The normal adult ovary measures approximately 3-5 cm in length, 1.5-3 cm in width, and 0.5-1.5 cm in thickness; however, ovarian size is reported more often in terms of volume, or length × width ×  thickness ×  0.523. Normal ovarian volume in the menstruating females is 5-15 mL, with an approximate mean of 10 mL; however, measurements as high as 22 mL have been reported in normal ovaries.

A thin, fibrous layer, called the tunica albuginea, encapsulates the ovary. Within the capsule lies the ovarian stroma, a combination of fibroblasts, smooth muscle cells, arteries, veins, lymphatics, nerves, and follicles. The stroma is typically divided into a cortex and medulla. The medulla is a highly vascular region that is supplied by the ovarian artery and branches of the uterine artery, which enter the ovary via the broad ligament. From here, smaller arteries and arterioles penetrate the cortex. The peripheral zone, or cortex, is predominantly composed of follicles and spindle-shaped fibroblasts and smooth muscle cells.

In women with female fetuses, by the seventh month of gestation, primordial follicles have begun to develop in the fetal ovary. They consist of primary oocytes that are encapsulated by single layers of follicular cells. At birth, each ovary contains approximately 400,000 primordial follicles. After puberty and during each ovarian cycle, a number of follicles are hormonally stimulated to begin maturing. Usually, only a single follicle completes the process. Follicular cells proliferate and differentiate into the granulosa cell layer. The surrounding ovarian stroma differentiates into thecal cells (internal and external layers). Cell layers play a complex role in the development of the follicle; in hormonal variations during the menstrual cycle; and, ultimately, in ovulation.

Presentation

Most patients in whom polycystic ovarian syndrome is ultimately diagnosed initially present with infertility, amenorrhea, or irregular menses. Although most woman present in their 20s or 30s, polycystic ovarian disease can affect females of any age, from menarche to menopause. Findings in almost 75% of patients meet the radiologic criteria for polycystic ovarian syndrome. Primary amenorrhea is a well-known but uncommon presentation.

Although infertility is the most common presentation in affected patients, polycystic ovarian syndrome may be associated with obesity and insulin resistance, among other symptoms. A number of patients are identified only when they present with unrelated complaints; these patients may believe the symptoms that are associated with the syndrome are not of sufficient clinical significance to warrant medical attention.

A second population of patients presents with systemic signs of androgen excess — namely, hirsutism, acne, or male-pattern baldness. In approximately one half of the patients, sonograms show polycystic ovaries.

Additionally, a significant number of patients with unrelated complaints are incidentally found to have polycystic ovaries. Further detailed clinical evaluation reveals that approximately one half of the patients in this group have typical signs and symptoms of the syndrome (ie, hirsutism, acne, infertility) and that one quarter have related symptoms such as obesity, irregular menses, or insulin resistance. The remaining one quarter of the patients may not have any clinically evident abnormality.

Preferred Examination

Polycystic ovaries are most often diagnosed by means of laboratory studies. The initial screening tests may include determinations of the blood serum levels of thyroid-stimulating hormone (TSH), FSH, LH, and prolactin (PL). The ratio of the FSH level to the LH level is useful in the diagnosis. TSH or PL levels may be useful in identifying an etiology, such as hyperthyroidism or a prolactinoma. In some patients, testosterone and dihydroepiandrosterone sulfate (DHEAS) levels or a progesterone challenge are useful.^3,21

Typically, a radiologic evaluation for polycystic ovaries is reserved for patients who have equivocal laboratory findings. However, radiologists make a significant number of incidental diagnoses. Should the radiologist's assistance be requested in the diagnosis of polycystic ovarian syndrome, the imaging method of choice is transabdominal and/or transvaginal ultrasonography. Magnetic resonance imaging (MRI) is useful as an adjunct; however, although MRI is more sensitive than ultrasonography, its findings are less specific.

Polycystic ovarian syndrome is not a primary disease process. When polycystic ovaries are discovered at radiologic examination, further diagnostic tests are needed to determine the etiology.

Limitations of Techniques

When the laboratory values are interpreted together with a thorough history as well as physical examination findings, they are useful in the diagnosis of polycystic ovaries. In some patients, such information may lead to a specific cause of the ovarian dysfunction (eg, hyperprolactinemia). When hormone levels do not provide adequate information, ultrasonography may prove useful; however, in the absence of correlative information, the significance of the radiologic findings is difficult to determine. The primary limitation of ultrasonography is that a radiologic diagnosis of polycystic ovaries does not reveal the underlying pathology, if it exists. Further studies are usually necessary to determine the cause of the radiologic finding.

Differential Diagnoses

Endometrioma/Endometriosis
Pituitary Adenoma

Other Problems to Be Considered

Virilizing tumor, adrenal or ovarian
Cushing syndrome
Idiopathic or familial hirsutism
Ovarian hyperthecosis
Hilar cell hyperplasia
Premature ovarian failure
Insulin resistance and type II diabetes mellitus
Adrenal hyperplasia (congenital or adult onset)
Hyperandrogenism and androgen-producing tumors
Hyperprolactinemia

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