Virtually all patients with PCOS will have at least subtle laboratory abnormalities. The reported results may be only on the upper limits of the ‘normal range,’ showing only a tendency, not a discrete abnormality. Often a pattern will emerge after considering a group of tests together. These subtleties may reveal dysfunction in the control mechanisms of the hypothalamus, pituitary, ovary and adrenal (HPOA axis) working collectively. In distinction, serious pathology may be more evident by a marked elevation, or suppression of a single test.
Though the value of repeated blood testing for the same hormones could be questioned, it is recommended that each PCOS patient have an initial, relatively comprehensive evaluation and interpretation by an individual familiar with this testing. In the following list, normal levels will not be given because of the marked variations between laboratories and techniques. Any level that is twice the upper or lower limit of normal is particularly important and may indicate a serious problem. The marginally elevated test is almost always dysfunctional, rather than pathologic. As a rule, endocrine testing, other than a pregnancy test, is probably best performed in the morning, soon after a spontaneous or induced menses. The days around ovulation or mid-cycle should be avoided. Hormonal evaluation in patients on oral contraceptive will often give misleading results with suppression of gonadotropin, ovarian steroid and SHBG levels. It is of limited value to determine these hormone levels in patients on the pill. Glucose and lipid evaluation should be in the morning after fasting (no food or drink after midnight the night before).
There have been a large number of tests and procedures used in the past for evaluation of PCOS. Listed below are a number that may be seen and should provide sufficient data for a very comprehensive investigation. All may not be useful in all patients.
While androstenedione may be the steroid most often elevated in PCOS evaluation, its lack of specificity in determining the source of hyperandrogenism, or modifying its treatment, probably make measurement of this hormone unnecessary. Androstenedione is almost totally and equally produced from the adrenal gland and ovary.
Dehydroepiandrosterone (DHEA, DHA) and Dehydroepiandrosterone sulfate (DHEAS) are relatively weak androgens and are almost exclusively of adrenal origin. Although produced in relatively large amounts, they have little potency. They can be converted in the ovary and peripheral sites to more potent androgens. Adrenal tumors often produce very large amounts of DHEAS and are seldom associated with only modest elevations. A DHEAS measurement can be used to determine whether there is an adrenal component to PCOS and whether the patient may benefit from a trial of low dose corticosteriods. Women with 21-hydroxylase deficiency (described below) may not have an elevated DHEAS.
Follicle Stimulating Hormone (FSH) Luteinizing Hormone (LH) FSH and LH are gonadotropins, hormones made in and released from the pituitary gland that control the function of the gonads, the testes and ovaries, The absolute level of each, as well as the LH:FSH ratio, can offer significant insight into the PCOS patient. Clearly increased LH is related to, if not diagnostic of, PCOS. Traditionally, the diagnosis of PCOS has been made when the LH to FSH ratio is over three. A relatively recent change in the type of assay used to measure LH has resulted in lower reported LH levels. Still, finding a higher LH than FSH in the early part of the menstrual cycle is a hallmark of PCOS. The alteration in the LH: FSH ratio is more likely to be evident before, rather than after, a progestin challenge. Some PCOS patients, especially those who are markedly obese, may have gonadotropin levels that are suppressed rather than elevated. Some experts suggest that measurement of LH and FSH is of limited value. It would seem that confirmation of an elevation in LH is very diagnostic of PCOS. The measurement of FSH will also permit the diagnosis of an occult ovarian failure where the FSH levels are particularly elevated. This is a diagnosis, which is important not to miss in therapy planning.
17-Hydroxyprogesterone (17-OHP4) is a hormone produced by the corpus luteum formed from the follicle after ovulation and by the adrenal gland. A clinical picture virtually identical to PCOS can be caused by an isolated, inherited disorder of the adrenal glands where an enzyme responsible for interconversion of steroids is missing. This results in a build-up of androgens and thus, PCOS findings. A measurement drawn at 8 to 9 a.m. in a fasting state in the follicular phase will identify most cases of 21-hydroxylase deficiency. Levels should be over twice the normal range. While not as sensitive as dynamic testing using synthetic ACTH, it is much easier.
Insulin levels should be obtained fasting and possibly after a glucose challenge. Insulin resistance may be present in advance of or without, elevated glucose level. There is controversy about what levels constitute hyperinsulinemia and what the diagnosis of insulin resistance. Most with fasting insulin levels above 20 are hyperinsulinemic and may be candidates for insulin altering drugs depending on the clinical situation. Prolactin is a hormone produced by the pituitary gland level that assists in milk production for lactation. The hormone is, by necessity, elevated in pregnancy and during breastfeeding. Prolactin suppresses ovulation and is one of the reasons why breastfeeding women are relatively infertile.
Prolactin levels maybe elevated outside these times (hyperprolactinemia) and associated with breast secretion (galactorrhea). Hyperprolactinemia, regardless of PCOS, is a relatively frequent cause of infertility and usually can be easily and successfully treated. Hyperprolactinemia has been associated with increased production of DHEAS, which is reversed after treatment with bromocriptine (Parlodel). While a direct effect is possible, another mechanism may be indirect from conversion of DHEA into estrone in the periphery. Estrogens are known to elevate prolactin levels through a mechanism in the central nervous system. Despite this fact, it is still not clear that the findings of PCOS and hyperprolactinemia, both relatively common disorders, are not coincidental. Potential functional causes of mildly elevated prolactin levels are drug use, anesthesia, stress, blood drawing, recent breast stimulation, breast examination and blood sampling around the time of ovulation. Hyperprolactinemia can be a sign of a prolactin producing pituitary gland tumor (prolactinoma). These are benign and usually easily treated with oral medications. Less often, hyperprolactinemia may be an indication of other structural abnormalities of the brain. Hyperprolactinemia is often found in patients with hypothyroidism and a TSH level should be obtained. Patients with over marginally elevated prolactin levels on repeat examination should be referred for magnetic resonance imaging, MRI.
Testosterone is the principal male hormone. More than 75 percent of circulating testosterone is derived from conversion of other steroids by the liver and skin. The remainder comes equally from the adrenal gland and ovary. Either the free or total testosterone level can be determined. The decision on which to obtain should be based on availability and cost of the test and personal preference of the physician. Total testosterone is more likely to be related to overall metabolic status and is less specific than free testosterone. Marked elevation of either free or total hormone is equally worrisome and warrants complete investigation.
Thyroid Stimulating Hormone (TSH)is the single most important measurement of thyroid function. Except in the relatively uncommon disorder of central suppression, where both TSH and free thyroxine are suppressed, TSH is diagnostic of both hyper- and hypothyroidism. A free thyroxine level may be added to a repeat TSH measurement when the initial TSH measurement is low. There is no clinical utility in the “thyroid panel,” or total thyroxine measurement, and these tests should be abandoned. TSH is the method of choice to monitor thyroid replacement therapy. It should be noted that a four- to six-week period is necessary for equilibrium to be reached. Patients on replacement should be titrated to the mid-normal TSH range. Overly supplemented patients are at risk for osteoporosis and heart disease.
Other useful laboratory determinations
Comprehensive biochemical profileis the designation for a group “panel” of blood tests that evaluate the body’s overall metabolism, salt and fluid balance. Various electrolytes (salts), fats, glucose and liver enzymes are measured. Overall these tests are used to evaluate the function of the liver and kidney. Some therapies used to control PCOS potentially have adverse effects and their use needs to be monitored periodically. This relative inexpensive test obtained from a single blood sample. It is best to be obtained after fasting.
Glucose and Glucose Tolerance Testing (GTT) or GTT may be considered on PCOS patients, especially those over 120 percent of ideal weight, have first degree relatives with diabetes, have elevated serum lipid levels, or those having delivered over a nine-pound infant. The American Diabetic Association (ADA) has designated individuals with fasting glucose levels over 126 mg/dl, as diabetic. A new category is used to describe individuals with fasting levels 110-126 mg/dl, as having impaired glucose tolerance. The term “Type 2 diabetes” is used to describe insulin resistance that has resulted in elevated glucose levels and has replaced the older terminology of “late,” or “adult onset.” No distinction is made for insulin dependency. The ADA recommends a two-hour screening after a 75 gram glucose load, as definitive testing, but a one-hour 50 g. test is often used in most obstetric practices and will probably yield similar results.
A Hemoglobin A1c blood test is a unique marker of how well diabetes is controlled. There is usually no reason to measure this in a PCOS patient unless diabetes or glucose intolerance is confirmed.
A Lipid panel is a useful test for the general evaluation of health risks in all patients, but is of special importance in PCOS. These individuals have a distinct tendency toward abnormalities. When abnormalities are found, treatment can be prescribed which may alter significantly the risk of heart attach and stroke. The panel includes tests that measure the concentration of cholesterol, triglyceride and relative concentration in lipoproteins (the good and bad cholesterols).
Sex Hormone Binding Globulin (SHBG) is a useful, but not commonly used, marker of PCOS. Low levels are a relatively good indicator insulin resistance. Age, weight, diet, steroid and thyroid hormone levels, all affect the concentration of SHBG. Hypothyroidism is associated with a decrease in SHBG. There is an inverse correlation between body mass and SHBG in women, but not men. Women with high waist-hip ratios have lower SHBG, possibly relating to correlation with hyperinsulinemia. While there is a clear direct dose related effect of estrogen administration, it is much less clear what effect concomitant use of progestational agents has on SHBG levels.