UNDERSTANDING INFERTILITY
stigmata such as acanthosis nigricans. Using the Ferriman-Gall-
wey score to assess hyperandrogenism is problematic for multiple
reasons, and it is better to assess for “patient-important” hirsutism.
Lab evaluation includes ruling out other conditions as above, some
measure of hyperandrogenism, as well as a 2-hour glucose tolerance
test and a fasting lipid panel. Measuring androgens in women is
tricky. It includes either measuring a free testosterone, or a com-
bination of total testosterone and SHBG, but most assays are not
very accurate in women, and circulating androgen levels may not
be representative of clinical findings. The third assessment would
be a pelvic ultrasound to evaluate ovarian morphology.
Patients with PCOS are at increased risk for other medical
conditions, including pregnancy complications (such as gestational
diabetes and preeclampsia), metabolic syndrome, obstructive sleep
apnea, non-alcoholic fatty liver disease and depression. Patients
with PCOS are also at increased risk for developing diabetes, lipid
abnormalities and endometrial cancer due to prolonged unopposed
estrogen exposure.
Treatment depends on whether the patient desires to get pregnant
or not. For all obese patients, lifestyle changes, specifically weight
loss, will help to normalize some of the hormonal abnormalities,
mainly by decreasing hyperinsulinemia. Studies have shown that
a weight loss of as little as 10% can be enough to ensure regular
ovulation.
If a patient desires pregnancy, ovulation induction with either
clomiphene (a selective estrogen receptor modulator) or letrozole
(an aromatase inhibitor) helps with ovarian follicle growth and can
lead to regular ovulation. Clomiphene is FDA approved for this
indication, and doses up to 250 mg/d given on cycle day three to
seven are being used to induce ovulation. Two-thirds of patients
with PCOS and no other fertility issues will conceive within three
ovulatory cycles. Side effects include headaches, hot flashes, vaginal
dryness, thin endometrial lining and thick cervical mucus. Though
currently non-FDA approved, Letrozole has been shown to result
in a significantly higher life birth rate, specifically in women with
PCOS. Letrozole also has less side effects and is usually well-toler-
ated by patients, with less risk for multiple gestation compared to
clomiphene, and no increased risk for birth defects or pregnancy
complications. In women who are resistant to clomiphene or letro-
zole, a longer course can be given, or dexamethasone can be added.
Superstimulation with gonadotropins is last resort, as it comes with
a high risk for multiples, as well as risk for ovarian hyperstimulation.
A better option in these patients would be to proceed with IVF,
where the number of transferred embryos can be controlled and
the risk for multiples decreased.
decreasing the risk for endometrial hyperplasia and cancer - is the
most important goal. This can be achieved easily by starting hor-
monal contraception in various forms. Estrogen- and progestin-con-
taining methods have been shown to regulate cycles faster and help
more with acne and hirsutism, due to the combined effects of these
two hormones on androgen production. There does not seem to
be a difference in any of the available oral contraceptives, as long
as they contain at least 20 mcg of estrogen. With that being said,
some believe that a 30 mcg estrogen-containing pill may work faster
than a lower-dose pill. Some progestins are more androgenic than
others and should be avoided. Taking the hormonal contraception
continuously (without the historically reported one week break)
can help suppress the androgens even more. In women where estro-
gen-containing contraceptives are contraindicated, progestin-only
contraception can be used (including cyclic medroxyprogesterone
acetate, depo medroxyprogesterone acetate or the progestin-re-
leasing IUD). Any of the contraceptives can be combined with
anti-androgens, if hirsutism and acne are the main complaint, and
monotherapy with contraceptives does not significantly alleviate
symptoms over a 6-month period.
Anti-androgens commonly used include spironolactone, fin-
asteride and flutamide. All of these are not FDA approved for this
indication of hirsutism. They need to be used in conjunction with
reliable contraception, as they can cause undervirilization in a
male fetus if pregnancy occurs. Although Metformin is often used
for PCOS, it is not FDA-approved for PCOS-related menstrual
dysfunction or hirsutism.
Another treatment option for women with PCOS who desire to
avoid long-term hormonal therapy is laparoscopic ovarian drilling
(LOD). A laser or needle electrode is used to cause thermal damage
to the ovarian stroma to decrease androgen production, sparing the
cortex with the antral follicles at the same time. This method is not
used as often anymore, since ovulation induction medications are
available. This procedure involves surgical risks, risk for adhesion
formation with risk for pelvic pain, potentially decreasing ovarian
reserve, as well as only temporary improvement (effects lasting
two to 10 years).
Mechanical hair removal techniques such as shaving, waxing,
laser removal and electrolysis can be used until the hormonal meth-
ods take effect.
Diagnosing PCOS in adolescents and peri- and postmenopausal
women requires additional criteria.
Dr. Krause is a practicing reproductive endocrinologist at Fertility and Endocrine
Associates.
If a patient does not desire pregnancy, cycle regulation - thereby
SEPTEMBER 2019
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