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7400 Fannin St., Suite 1180
Houston, Texas 77054 Phone (713) 790-9900 Fax (713)-790-9901 |
Robert
B. McWilliams, MD
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INFERTILITY MALE
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POLYCYSTIC OVARIAN SYNDROME (PCOS)Polycystic Ovarian Syndrome (PCOS) is the most common endocrine disorders of women of reproductive age. Affecting approximately 6-10% of all premenopausal women and approximately 70-90% of women with irregular menstrual cycles, the classic symptoms of this disorder consist of irregular periods, infertility, and excessive body and facial hair. As a consequence of the overproduction of androgens (male hormones) by the ovaries, additional symptoms of acne, obesity, and male-pattern hair loss are seen together with symptoms of anovulation like heavy menstrual flow and erratic, unpredictable onset of menses. Some patients may demonstrate very mild or no symptoms of this disorder, complaining only of irregular cycles. Other patients may demonstrate all of the classic symptoms mentioned above. Definition of PCOSPolycystic ovarian syndrome (PCOS) is derived from the morphologic (appearance) alterations that occur in the ovary. Failure to ovulate (to rupture and release ovulatory eggs) on a monthly basis yields ovaries that are literally, "covered with ovarian cysts." This failure to ovulate healthy eggs results in infertility and a higher rate of miscarriage after a positive pregnancy test. Despite
our understanding of this most intriguing endocrine disorder of
women, scientists have been searching for an association among the
many facets of PCOS. Unfortunately, the pathophysiology of the various
disorders remains unknown. In the past, it was common for a woman
with infertility to have this diagnosis made during an infertility
evaluation. Today,
if the consequences of this disorder are left unattended, these
patients, infertile or not, will develop severe clinical problems.
Recent PCOS ResearchRecent research has found growing concern that PCOS is also associated with hyperinsulinemia (excess production of insulin by the pancreas), insulin resistance, dyslipidemia (abnormality of metabolism of fats), and hypertension. Risks of developing type 2 diabetes (non-insulin-dependent) and possibly, premature cardiovascular disease is higher in these patients with insulin resistance. Other consequences of anovulation include carcinoma of the endometrium and possibly carcinoma of the breast. These facts have lead to a new attitude towards this common female problem highlighting its legitimate place in today's "modern preventive health care of women." PCOS and Insulin ResistanceInsulin resistance, characterized by a decrease in the ability of insulin to stimulate glucose uptake to muscle and fat cells, as well as to inhibit glucose production by the liver is a common feature of women with PCOS. Up to 40% of women with PCOS demonstrate some degree of impaired glucose tolerance as a result of insulin resistance. A sign of severe insulin resistance exists known as acanthosis nigricans, a condition in which dark velvety patches appear on the skin. These areas are usually seen around the back part of the neck ("ring around the collar") and in other areas of the body where the skin folds on itself forming creases. It appears likely that an inherent, probably genetically determined ovarian defect is present in women with PCOS, which makes the ovary susceptible to insulin stimulation of androgen (male-like hormone) production. The insulin resistance and hyperinsulinemia are primary events in PCOS that somehow lead to hyperandrogenism and the subsequent reproductive endocrine abnormalities. It goes without saying that the clinician must recognize the clinical impact of PCOS and undertake therapeutic management of all anovulatory patients to avoid these unwanted consequences. Use of birth control pills, insulin sensitizing drugs, changes in life style patterns, gonadotropin releasing hormone agonists, advanced diagnostic techniques and assisted reproductive technologies are currently increasing our understanding of this disorder. Our hope is to initiate preventative measures early in young women's lives (teenage years) that yield increased longevity with healthier and more reproductive outcomes. PCOS- DiagnosisDiagnosis of PCOS usually follows a high sense of suspicion in women with irregular cycles who demonstrate mild forms of hyperandrogenism and are having difficulty getting pregnant. To confirm the diagnosis, blood testing of "the brain to ovary and ovary to brain signals" are assessed on cycle days 3, 4 or 5. Measurement of FSH (follicle stimulating hormone), LH (luteinizing hormone), and testosterone give a characteristic pattern for the diagnosis of PCOS on most occasions. The level of LH is normally equal to FSH in women without PCOS. With this disorder, LH is often higher than FSH, up to 2-3 times, as well as high testosterone levels (> 50 ng/dl) revealing high ovarian production. Checking serum progesterone levels on cycle days 21-23 to confirm ovulatory function are unusually low (< 4 ng/dl), indicating ovulatory problems. Your clinician might also recommend an ultrasound evaluation of the ovaries. Insulin resistance can be determined by obtaining a blood sample after a 12 hour fast for insulin and glucose. A glucose/insulin ratio of < 4.5 will be used to define insulin resistance. Other tests that might be used to help establish the diagnosis include a C-peptide and a glycosolated hemoglobin (HbA1C). All
right, now that I have your attention, how does PCOS affect a woman's
fertility? By affecting ovulation. These women do produce estrogen
from the ovaries in addition to testosterone, but the levels of
estrogen are lower than expected at the time of ovulation. Because
of the high level of LH and testosterone, follicular suppression
is caused within the ovary yielding poor or no ovulation with subsequent
loss of progesterone. Without a properly developed, healthy, fertilizable
egg and without estrogen and progesterone to secure a well-developed
endometrial bed for the ensuing pregnancy, infertility results.
In some women, an attempt to ovulate a poorly developed egg late
in the cycle yields a miscarriage from "a blighted ovum." And how does insulin resistance play a role in infertility? Again, by affecting ovulation. Researchers now have found that high levels of insulin can stimulate the activity of enzymes that are pivotal to the manufacture of androgens in the ovary. They have also discovered alterations or defects of these same enzymes that make them susceptible to over stimulation by insulin. Consequently, high levels of insulin or over stimulation of androgen receptors by insulin leads to follicular atresia (suppression) of early developing eggs long before ovulation. Therapeutic options of PCOS depend on the severity of symptoms and the woman's goal. Does the patient desire elimination of excess hair and/or acne? Does she desire regular periods with normal bleeding? Does she desire pregnancy? Is she at high risk of the metabolic abnormalities associated with this disorder? PCOS TreatmentMany treatment plans exist for PCOS. Among the most common are 1) weight loss, 2) hormonal manipulations, 3) surgical treatments, 4) steroid supplementation, 5) spironolactone, and more recently, 6) insulin sensitizing medications. Your particular treatment plan will depend on your goals. Today, we are truly entering a new era in our understanding and management of women with polycystic ovaries and hyperandrogenism. We now have a real opportunity "to make a difference in others lives" by affecting the quality and quantity of life to be experienced by these patients. Let us not only correct specific clinical consequences of anovulation but, let us also reduce major adverse effects on overall health.
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