PCOS Management – An Update
There has long been confusion as to how to properly diagnose PCOS. Most reproductive specialists follow the guidelines established at the 2003 Rotterdam, Netherlands Conference on PCOS. The agreed upon criteria for establishing a diagnosis of PCOS is the presence of two out of three of the following criteria:
Irregular or absent ovulations
Clinical or laboratory evidence of excessive male hormone production.
Ultrasound evidence of high antral follicle counts on the ovaries.
It is important to note that many of the criteria often associated with PCOS such as obesity, alterations in the ratio of LH to FSH, and insulin resistance are not part of the diagnostic criteria for establishing a diagnosis of PCOS. Patients with PCOS may present to the gynecologist’s office at different times in their lives, and with totally different needs. For example, young patients may be brought by their parents for help with management of acne, one of the common effects related to increased circulating male hormone. Others may present for evaluation of fertility potential, realizing that extreme menstrual irregularities are associated with failure to ovulate and thus infertility. The remainder of this communication will address individualized management of the PCOS patient, based upon the most current available information.
Very often patients with PCOS present to their physician with skin complaints such as acne, or excessive facial or body hair. If these women are not actively trying to conceive, management should consist of decreasing the amount of circulating male hormone as well as blocking the effect of male hormones at the level of the hair follicle. These goals can be achieved through the use of an estrogen/progestin birth control pill, which will act by suppressing the secretion of luteinizing hormone (LH), which drives male hormone production by the ovary, and by increasing the amount of sex hormone-binding globulin (SHBG). The net effect of increased (SHBG) is to bind more free male hormone, which results in less hormonal effect on the skin, decreasing hair growth and acne.
In addition, anti-androgens such as spironolactone, flutamide or finasteride may be used in conjunction with the birth control pill to decrease hair growth and acne. Physical approaches to hair removal such as laser treatment, waxing, shaving, depilatories or laser treatment may be helpful.
PATIENTS WHOSE PRIMARY CONCERN IS CONTROLLING IRREGULAR OR HEAVY MENSTRUAL BLEEDING AND/OR PREVENTING ABNORMALITIES OF THE UTERINE LINING
There is very strong support in the scientific literature for “lifestyle modifications” such as diet and exercise for PCOS patients who are overweight. As little as 5%-10% reduction in body weight can help to restore more normal menstrual function.
Oral contraceptives have been used for many years to provide regular menstrual cycles and protect the uterine lining from excessive thickening.
Insulin sensitizing agents such as metformin may reduce androgen production and improve menstrual regularity. However, it may take up to 6 months for normal ovulation to return.
Intermittent therapy with progestin every 2-3 months can be used to prevent the uterine lining from becoming excessively thickened or pre-cancerous.
PCOS PATIENTS WHO ARE INFERTILE
Preconception lifestyle modifications including diet and exercise are an important part of treatment in preparation for pregnancy. Obesity is a significant risk factor that is related to failure to ovulate, pregnancy loss, and late pregnancy complications. Weight loss of 5%-10% of body weight results in improved responsiveness to all ovulation induction medications.
The use of insulin sensitizing agents such as metformin as a first line of treatment is controversial. The response to metformin in terms of inducing ovulation is quite slow, with at least several months of continuous treatment required before ovulation is achieved. The use of oral ovulation induction agents such as clomiphene, letrozole, or injectable gonadotropins is a more direct treatment, which is likely to achieve successful ovulation more quickly than insulin sensitizing agents. A recent review of all publications on this subject suggested that combining an insulin-sensitizing agent with clomid led to better pregnancy rates than clomid alone. However, insulin-sensitizing agents do have significant gastrointestinal side effects and require periodic monitoring of liver and renal functions. Combining metformin with injectable pituitary hormones (gonadotropins) for IVF does not seem to improve pregnancy rates, but does reduce the chances of ovarian hyperstimulation.
Clomiphene citrate (clomid), the most widely used fertility drug is still considered to be the first choice for the majority of infertile PCOS patients. Seventy five to eighty present of patients with PCOS will ovulate while being treated with clomid.
Injectable pituitary hormones (gonadotropins) are the treatment of choice for infertile PCOS patients who have failed to ovulate or conceive with clomid treatment. PCOS patients are at significant risk of ovarian hyperstimulation when gonadotropins are used and it is for this reason that careful monitoring is required.
Letrozole, an oral agent classified as an aromatase inhibitor may be used successfully in PCOS patients. There is some evidence that the incidence of twins may be lower than clomid (5% vs. 10%), and monthly chances of successful pregnancy may be higher. However, letrozole is not yet FDA approved and there is not enough data at this time to recommend it as a first line treatment in PCOS patients who are infertile.
Assisted Reproductive Techniques may be used for infertile PCOS patients who have failed to achieve a successful pregnancy with other treatments. Controlling the ovarian stimulation for IVF is difficult in the context of PCOS. However, a carefully thought out strategy of ovarian stimulation will minimize the chances of ovarian hyperstimulation.
LONG TERM OUTCOMES
PCOS patients are at risk for carbohydrate intolerance, type 2 diabetes, hypertension, and hyperlipidemia. Lifestyle management (diet and exercise) will lead to weight control and reduced risks for developing diabetes, hypertension and vascular consequences of hyperlipidemia. For patients with impaired glucose tolerance or type 2 diabetes, metformin may be used. There is insufficient evidence at this time to recommend long term metformin or alternative insulin sensitizing agents in the absence of proven glucose intolerance or type 2 diabetes.
Management of PCOS requires individualized, personalized care. Treatment must be tailored to the patient’s age, circumstances, and severity of her condition, in conjunction with her personal needs.