POLYCYSTIC OVARY SYNDROME | Current Thoughts

Polycystic Ovary Syndrome affects more than 5 million women most of whom fail to realize their potential danger.  While this leading cause of infertility seems to identify it as principally as a gynecologic disorder, PCOS significantly increases the risk for heart disease, stroke, diabetes and more.

Unfortunately the name suggests the major manifestation involves cysts within the ovary.  Actually this feature probably represents a complication of the underlying disease process and need not be present for the diagnosis.  In fact these so-called ovarian cysts do not even represent true cysts but rather immature follicles that fail to mature and release an egg.  Normal ovaries often demonstrate these findings which by themselves do not indicate any medical disease.

Subtle hormone abnormalities remain central to PCOS.  It ranks as the most prevalent endocrine disorder in women between ages 18-44 striking between 6-10% of this population.  The frequency of this condition parallels the ever increasing epidemic of obesity.

HISTORY

This recently identified abnormality was first described by Drs. Stein and Levanthal in 1935 as a rare disorder whose manifestations involved infertility due to a lack of ovulation and excessive facial and body hair together with enlarged, polycystic ovaries.  Medical advances since that time provoked controversy about the cause, diagnosis, symptoms and treatment.

HORMONE EXCESS AND RESISTANCE

Currently it appears fundamental abnormalities of PCOS revolve around excessive concentration of male hormone, heightened insulin production and  resistance to the action of insulin by the muscles and fat.  All of the other associated findings, including the ovarian cysts, arise as a consequence of these basic hormone issues.  Unfortunately the condition’s name continues to misrepresent reality and confuse both patient and doctor alike.

GENES

Typical of most disease, PCOS also demonstrates a considerable although complicated genetic component.  Transmitted from either parent, the clinical expression varies significantly even among siblings and often seems to hinge on body weight.  Interestingly parents of those affected by PCOS also appear at elevated risk for high blood pressure, heart disease and stroke.

Aside from genes, a host of other factors acting on the fetus still within the mother’s uterus may impact on later development of this disorder.  Serious discussion surrounds the role of endocrine disrupters possessing weak hormone activity such as the omnipresent bisphenol a ubiquitously present in food and drink containers.

SYMPTOMS

Symptoms begin to appear at puberty or alternatively in women during their twenties and thirties.  Estimates suggest 70% of individuals completely escape medical detection.  Principal manifestations include abnormalities involving elevated levels of male hormone and insulin.  These occur together with irregular secretion of gonadotropins – LH and FSH – from the pituitary gland located in the brain that controls development of follicles and their subsequent release from the ovary.

Heightened levels of male hormone such as testosterone, androstenedione, dihydrotestosterone and others often lead to excessive growth of hair on the upper lip, sideburn, neck, chest, back, abdomen and thighs.  Contrariwise thinning of the hair on the scalp regularly occurs and may be more psychologically traumatic.  Another unfortunate side effect of this hormonal imbalance involves acne, possibly severe, that extends well beyond the customary age group.  Quite often there are no obvious clinical signs of androgen excess; it may be apparent only on blood examination.

Some women also develop thick, velvety, brown skin on the sides of their neck, under the arms or even on top of the knuckles.  This cosmetic but not inherently dangerous condition known as acanthosis nigricans further testifies to the insulin resistance.  An excessive number of skin tags occur especially on the side of the neck, under the arms and in the groin.

HORMONE IMBALANCE

The excess male hormone plays havoc with the ovary and in conjunction with insulin resistance leads to a wide array of menstrual abnormalities.  Some women never begin having menstrual cycles while in others periods cease altogether after awhile.  More commonly women have fewer than nine periods a year.  Many women suffer from excessive menstrual bleeding occurring at irregular intervals which generally signals a problem with ovulation.

Many but not all of the women experience reduced fertility.  Among those who do become pregnant, an increased rate of fetal loss and perinatal mortality await.  And for the mother risks include gestational diabetes, pregnancy induced hypertension and pre-eclampsia which combines elevated blood pressure with water retention and protein in the urine possibly progressing to blurred vision, headache and overwhelming fatigue.

Polycystic ovaries, once thought inherently necessary for the diagnosis of PCOS, occur frequently in normal women.  To reduce misdiagnosis, some experts who previously deemed no fewer than 12 cysts as a criterion, have increased that figure to in excess of 25.  Cysts tend to occur just under the surface of the ovary and are visible as a “string of pearls” on vaginal ultrasound examination.  In any event the presence of these cysts which average about ¼ inch in diameter tends to confirm rather than establish the diagnosis.

POTENTIALLY ASSOCIATED DISEASES

Most importantly the hormone abnormalities perhaps coupled with central nervous system malfunction in the hypothalamus lead to an assortment of medically important abnormalities.  Associated with PCOS are obesity, pre-diabetes, type 2 diabetes, obstructive sleep apnea and a form of hepatitis due to fatty infiltration that may progress to cirrhosis.  Other frequent associations include anxiety, depression, hypertension, heart disease and stroke.  Impaired activity of blood vessels referred to as endothelial dysfunction boosts the likelihood of narrowing of the carotid arteries and clogging of the coronary arteries.  Elevated cholesterol levels and a tendency to blood clot formation further increase the potential for harm.

Additionally because of the hormone imbalance, PCOS increases the probability of abnormalities of the tissue lining the uterus.  While some of these changes evidence only as excessive thickness others result in degeneration to uterine cancer.  There may be a slight increase in the risk of ovarian cancer compared to the general population.

Thyroid abnormalities in the form of autoimmune thyroiditis also occur.

DIAGNOSIS

Unfortunately no readily available diagnostic test exists and blood evaluation of hormone concentration remains fraught with error.  Even the experts disagree on the core features necessary to establish the diagnosis.

How do we proceed
Now What?

TREATMENT

Prior to beginning a treatment regimen, several conditions that mimic the features of PCOS must be excluded.  The most frequent imitator is congenital adrenal hyperplasia that manifests many of the same characteristics as PCOS.  At least a routine laboratory test exists to exclude this condition.  Other abnormalities that may be confused with PCOS include an underactive thyroid gland, excessive production of prolactin from the pituitary gland, premature menopause and lack of periods due to anorexia, excessive exercise or certain medicines.

Treatment varies depending on the most bothersome symptom.  For many women attention to diet and weight loss may suffice to restore some normality to their internal hormonal milieu.  This often results in improved quality of life, lower cholesterol, regular periods and perhaps even ovulation.  Pregnancy rates increase dramatically as a consequence of weight reduction.  As little as 5% loss in body mass may result in major correction to a point where the need for diabetes therapy may be discontinued.

A more healthy lifestyle provides a buffer against the cardiovascular related issues.  It is important to emphasize that the onset of menopause fails to completely erase the health burden of PCOS.

MEDICAL TREATMENT

At times medical therapy may be justified.  A commonly prescribed anti-diabetes medicine provides some benefit for those with PCOS even in the absence of elevated blood sugar.  Metformin reduces both insulin and testosterone and by these actions may assist with weight loss, lead to normalization of the menses and increase fertility.

When women lack any menses or experience irregular heavy periods, combination oral contraceptives may offer significant assistance.  Both estrogen and progestin containing therapy improve many of the underlying hormone issues.  As an additional benefit restoration of normal menstrual cycles reduces the risk of endometrial cancer.  Improvement in excessive hair growth and acne require months before becoming apparent.

While many women with PCOS complain of infertility, some women remain fertile and require contraceptives for their more traditional role.  Interestingly up to 40% of women with amenorrhea – lack of any menstruation – may still ovulate and become pregnant in the absence of appropriate precautions.

ALTERNATIVE MEDICAL THERAPIES

At times oral progestin taken either regularly or intermittently may be sufficient to protect the lining of the uterus.  Alternatively a progestin containing IUD may be adequate.  Since certain progestins demonstrate androgenic activity, appropriate selection by the health care provider remains essential in order to secure a positive outcome.

Another popular medicine clomiphene or clomid acts as a selective estrogen receptor modulator.  It functions as an anti-estrogen when taken orally during the initial phase of the cycle and assists in egg maturation within the ovary.  Many consider it the most effective therapy for those women wishing to conceive.

A different approach involves an aromatase inhibitor prescribed mostly for women with breast cancer.  Letrozole or Femora prevents conversion of male to female hormone in the fat cells.  This agent seems at least as effective as clomiphene for those women desiring pregnancy.

A variety of other pharmaceutical products exist but fail to provide consistent results.  Over-the-counter inositol offers a potentially useful “natural” alternative of undetermined worth.

OUTDATED SURGERY

In a previous era, gynecologists routinely performed “wedge” resection of a portion of the ovary.  This older technique generally failed to provide sufficient  advantage to warrant the incidence of delayed complications.  On occasion a laparoscopic procedure known as ovarian drilling may be acceptable.  Puncturing then cauterizing several of the small ovarian cysts may result in resumption of spontaneous ovulation.  This should be considered as a final option only employed when everything else fails.

FINAL THOUGHT

In women without any specific complaint, opting for no intervention certainly remains acceptable.  However it is essential to remember the background increase in cardiovascular risk demands appropriate attention at least to diet and exercise.

 

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