Amenorrhea — Full Text

Amenorrhea means โ€œno menstrual periods.โ€  Anyone can miss a period now & then, even two in a row.  But once a woman goes 3 months without a period (or 6 months if periods have always been wide apart), we begin to look for the reason.  Note that we’re discussing women who previously had normal periods, not girls / women who have never had one yet (& we’re not addressing women on new methods of birth control that are obvious causes for menstrual irregularities).

As mentioned before, our first step is a pregnancy test.  We do this on everyone — even women using birth control, women who’ve been sterilized (tubal ligation), women who say they haven’t had sex.  We deal with all sorts of strange occurrences & confused people in our profession, & can’t risk missing the most obvious cause.  Also, even if our patient hadnโ€™t had a period for many months, & doesnโ€™t look pregnant, she may well have conceived just in the last 2 months

Menstrual periods are related to ovulation, which involves the brain & several different glands.  These produce a variety of hormones which we can measure.  Blood levels of Follicle Stimulating Hormone (FSH), Thyroid Stimulating Hormone (TSH), Prolactin, Estradiol (a form of estrogen), even Testosterone and other male hormones, can help us determine why periods have stopped.  See Ovulation for an explanation of how this system works, & the roles played by the brain and ovaries.

Assuming a pregnancy test is negative, we consider the following possibilities:

Causes of Amenorrhea

xxxCommon Causes (>90% of cases)xxxxxxUncommon Causes
โ€ข Functional (lifestyle factors; not dangerous)
โ€ข Polycystic Ovarian Syndrome (PCOS)
โ€ข Conditions of the Brain (Hypothalamus and xxxxPituitary Gland)
โ€ข Premature Ovarian Failure (Premature xxxxMenopause)
x
โ€ข Hyperthyroidism / Hypothyroidism
โ€ข Celiac Disease
โ€ข Type-1 Diabetes
โ€ข Various Tumors (brain, pituitary gland, ovary)
โ€ข Scars in Uterus (from surgery; or severe xxxxbleeding during childbirth)
โ€ข Congenital Adrenal Hyperplasia (CAH)

Diagnostic Approach

1.  The three most common causes of Amenorrhea, comprising over 90% of cases, are:

** Functional Amenorrhea This is caused by dysfunction of the brain’s Hypothalamus. It can be due to eating disorders, malnutrition, excessive exercise (running, ballet, gymnastics, figure skating), severe physical or psychological stress. The exact mechanisms are unexplained. “Functional” conditions are those in which no physical abnormality can be identified, and are not dangerous.

** Polycystic Ovarian Syndrome (PCOS) We suspect this in women with excess facial / body hair, scalp hair loss, acne; & obesity.  Similar body characteristics also occur with Congenital Adrenal Hyperplasia (CAH), but PCOS is much more common.

** Premature Ovarian Failure Technically defined as menopause occurring younger than 40 years old. Of course, a 41-year-old woman diagnosed with Menopause might certainly feel it’s premature.

We inquire about risks for Functional Amenorrhea (see above). If we identify some, this is the likely diagnosis.  BUT, we donโ€™t want to guess, so weโ€™d still order basic tests (see below).

Similarly, we look for signs suggesting PCOS.  If we find them, that would be our likely diagnosis, but weโ€™d still order basic lab tests.  Also, since Congenital Adrenal Hyperplasia (CAH) causes the same characteristics, we might order a blood test for 17-hydroxyprogesterone just to be sure (although CAH is most rare, & PCOS quite common).

Premature Ovarian Failure is easily diagnosed by noting other typical symptoms of menopause (hot flashes, vaginal dryness), and finding an elevated FSH blood test.ย  Its name has been changed from “Premature Menopause” to Premature Ovarian Failure, then modified to Premature Ovarian Insufficiency.ย  The latter is because 55% to 10% of women might still have some ovarian function from time to time.ย  They might even get pregnant.

2.ย  We obtain a medical history and perform a physical exam, focusing on the conditions above, and also seeking other clues such as recent weight loss or gain (Thyroid Diseases); milky discharge from nipples (Pituitary Gland Conditions); recent childbirth or operations on uterus (complications from them); or hot flashes (called “hot flushes” in the U.K., confirming Premature Ovarian Failure).

 We then order Blood Tests to rule out less common causes.  These include:

  • FSH, Prolactin, Estradiol, TSH.ย  Repeat the Prolactin test if it’s elevated (Pituitary Conditions).ย 
  • Testosterone & maybe other hormones (if suspect PCOS).
  • Maybe 17-hydroxyprogesterone for CAH

If abnormal TSH  โž™  more tests for Hyperthyroidism / Hypothyroidism

If both Prolactin tests elevated  โž™   Pituitary Gland Disease

  • Obtain MRI of brain to rule out large Pituitary Gland Tumor (uncommon)
  • A normal MRI with high Prolactin gives us a diagnosis of Microscopic Pituitary Tumor
  • We refer to an Endocrinologist for treatment. Lowering prolactin levels can often restore fertility.

If elevated FSH  โž™  Likely Premature Ovarian Failure (Premature Menopause)

  • especially if low Estradiol, & typical symptoms (hot flashes, dryness of vagina)
  • More tests may be needed to find the cause, especially if the woman is very young.  Weโ€™d refer to Gynecology; might refer anyway to confirm the diagnosis, which has major life implications

If low Estradiol & other labs normal (low Prolactin & FSH levels are considered normal)  โž™

  • Bood tests for Celiac Disease and Diabetes Type-1.ย  If negativeย  โž™
  • …then Strongly Consider “Functional” Amenorrhea.ย  Diagnosis clear if typical risk factors (eating disorder, excessive exercise, recent major weight loss or severe physical stress)
  • None of Aboveย  โž™ย  order MRI of brain to rule out Tumor (certainly order MRI if bad headaches or abnormal visual fields on eye exam)

We may want to confirm our impression of Functional Amenorrhea by treating with 10 days of progesterone pills, or a month of birth control pills (with its one week without hormones; iron tablets or dummy pills instead).  If that results in a menstrual period, our diagnosis is correct.

If symptoms of PCOS & labs all normal (maybe high Testosterone)  โž™ diagnose PCOS

  • If Testosterone very high (>150), or extreme masculine changes (increasing body / facial hair, deep voice, balding, increase muscles, breast shrinkage, clitoris enlargement  โž™  refer to Endocrinologist to rule out Tumors producing too much male hormone
  • Might order a 17-hydroxyprogesterone for CAH (same body appearance as PCOS)

If recent uterine surgery / severe bleeding during childbirth & all labs normal:

  • Refer to Gynecology to look inside the uterus by hysteroscopy (looking inside the uterus with a scope), for adhesions (scars) (Asherman Syndrome)
    • Also to evaluate Sheehan’s Syndrome: Pituitary Gland destruction from sudden loss of blood circulation during hemorrhage after childbirth
  • Often first try to produce menstrual bleeding by 10 days of progesterone pills, or a month or so of estrogen-progesterone birth control pills

See also Amenorrhea for the clinicianโ€™s condensed thought-process when face-to-face with a patient.

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