and PCOS Therapy
Ovarian Syndrome (PCOS), with insulin resistance, is one of the
most common endocrine disorders in women of reproductive age. Classic
symptoms consist of elevated male hormone levels leading to excess
body hair (hirsuitism), acne, a classic "pear" body shape,
and anovulation (lack of ovulation).
research has found that PCOS is associated with hyperinsulinemia
(elevated insulin levels) , insulin resistance, dyslipidemia, and
hypertension. Risks of developing type 2 diabetes (noninsulin-dependent)
and possibly premature cardiovascular disease is higher in patients
with insulin resistance.
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
in women with PCOS. Up to 40% of women with PCOS demonstrate some
degree of impaired glucose tolerance as a result of insulin resistance.
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.
(Glucophage) is an oral hyperglycemic (elevated blood sugar) agent
which acts primarily by improving the cells response to insulin.
Metformin is one of a unique class of drugs that exerts direct effects
on insulin resistance without affecting insulin secretion. Once
the insulin sensitivity is improved ovulation will resume.
is known to increase peripheral glucose uptake with some reduction
in basal hepatic glucose production. Its effects help lower the
elevated insulin levels in the blood stream of patients with insulin
has only been shown to exert its antihyperglycemic effect in the
presence of insulin. Because of its insulin-dependent mechanism
of action, Metformin is approved by the FDA for the management of
type II diabetes (non insulin dependent diabetes mellitus (NIDDM))
also known as adult onset diabetes.
treatment has been reported to decrease fasting insulin levels in
non diabetic obese women. Clinical studies have specifically examined
changes in ovulatory function in women with PCOS on Metformin (Glucophage
500 mg three times per day with meals) and confirmed increased frequency
of spontaneous ovulation, resumption of menstrual cyclicity, and
an improved ovulatory response to clomiphene.
previously infertile women with PCOS who were treated with Metformin
for six months conceived and delivered healthy infants. The advantage
of Metformin over traditional therapies for the treatment of PCOS
is twofold; 1) it corrects both metabolic and endocrinologic aberrations;
and 2) it permits resumption of normal endogenous ovulatory function,
with little or no risk of ovarian hyperstimulation or multiple gestation.
has been in clinical use in the United States since 1995. It can
produce gastrointestinal symptoms which are dose-related and tend
to resolve after several weeks. In the first few weeks of taking
Metformin, many patients will experience anorexia (loss of appetite),
nausea, diarrhea or abdominal discomfort which usually resolves
during continued treatment. (See the Bristol Myers Squibb Web site
for a full discussion of potential side effects)
testing at the initial screening- Hyperinsulinemic insulin resistance
will be determined by obtaining a blood sample after a 12 hour fast
for insulin, glucose and C-peptide levels. A glycosolated hemoglobin
(HbA1C), CBC with differential and platelets, and urinalysis will
also be evaluated. A glucose/insulin ratio of < 7.0 will be used
to define insulin resistance. A comprehensive metabolic panel profile
will be monitored at monthly intervals to follow renal and liver
correction of hyperandrogenism in women with PCOS may also be achieved
by interventions which improve insulin sensitivity and reduce circulating
insulin. Such measures include, but are not limited to weight loss,
dietary modifications and insulin-sensitizing medications. The use
of anti-diabetic drugs in PCOS represents a novel use of these agents.
management of PCOS should include diet control. Caloric restriction,
weight loss, and exercise are essential for the proper treatment
of the insulin resistant patient with PCOS. This is not only important
in the primary treatment of PCOS but in maintaining efficacy of
INFORMATION ON METFORMIN, INSULIN RESISTANCE, AND PCOS