Approach to secondary amenorrhea: Clinical sciences

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Introduction0:00–0:45

Before we begin, a quick terminology update. In 2026, an international group of patient advocacy and professional organizations introduced a new name for the condition previously known as polycystic ovary syndrome or PCOS.
PCOS is transitioning to polyendocrine metabolic ovarian syndrome, or PMOS. The new name was introduced because the condition involves much more than just the ovaries and can affect body weight, metabolism, mental health, skin, and reproductive function.
The old name emphasized ovarian cysts rather than the broader endocrine and metabolic features of the condition, which may have contributed to misunderstanding, delayed diagnosis, and inadequate treatment.

Assess for Pregnancy 0:45–1:41

As you watch the video, keep in mind that any references to PCOS refer to the condition newly named PMOS. The underlying disease process and management discussed in this video remain the same.
Secondary amenorrhea is defined as the absence of menses for more than 3 months in a patient who has a history of regular menstrual cycles, or greater than 6 months in a patient with a history of irregular menstrual cycles.
Secondary amenorrhea can be caused by dysfunction of the hypothalamus, pituitary, ovaries, thyroid, or uterus. Secondary amenorrhea is important because it can be a sign of systemic illness.

Other causes of amenorrhea1:41–2:14

It is associated with infertility and in some cases can lead to an increased risk of endometrial cancer, osteoporosis, or cardiovascular disease.
The first step in evaluating a patient who presents with secondary amenorrhea is to perform a focused history and physical examination.
You should also obtain some labs including HCG, FSH, estradiol, prolactin, and TSH. The first test you should always look at when evaluating menstrual abnormalities is the HCG, because if it's positive, you have a diagnosis of pregnancy, which is a common cause of secondary amenorrhea.

Primary ovarian insufficiency2:14–3:30

Here's a clinical pearl. Many hormonal contraceptives, such as continuous oral contraceptives or progestin containing intrauterine devices, have the desired side effect of amenorrhea.
This effect can persist for several months after discontinuation of these medications and can also affect the assessment of hormone levels.
Be sure to keep this in mind when evaluating a patient for amenorrhea. Once you have ruled out pregnancy, consider and assess for other causes of secondary amenorrhea.
The FSH level is a useful tool to triage patients as it helps to determine where the dysfunction lies along the hypothalamic pituitary ovarian axis.
Remember that an elevated FSH indicates that the ovaries are not producing enough estradiol, while a low FSH indicates that there might be dysfunction at the level of the hypothalamus or pituitary gland.
Let's start with ovarian dysfunction. In this case, the FSH is greater than 20, and history reveals a patient under the age of 40 with vasomotor symptoms, vaginal dryness, and possible mood changes, or a history of chemotherapy or radiation therapy.

PCOS3:30–5:45

The physical exam reveals vulvo vaginal atrophy, and the labs demonstrate a normal TSH and prolactin with low estradiol.
In this case, consider ovarian dysfunction and repeat the FSH and estradiol in 2 to 4 weeks. It is important to repeat these tests since the values can fluctuate significantly throughout the menstrual cycle and can be difficult to interpret when a patient has amenorrhea.
If the second set of labs confirms an FSH greater than 20 and a persistently low estradiol, that's primary ovarian insufficiency.
Here's a high yield fact. If patients with primary ovarian insufficiency, formerly called premature menopause, are not treated with systemic hormone therapy, they are at increased risk for osteoporosis and cardiovascular disease.
Next, let's talk about normal FSH levels in the setting of hypoandrogenism. The patient may present with a history of weight gain and will confirm that they are not taking exogenous androgens.
The physical exam may reveal a body mass index greater than 25, hypertension, acne, hirsutism, or antanthosis nigricans, while the pelvic exam is normal.
In addition, the TSH, prolactin, and estradiol are within normal range. If this is the case, think about hyperandrogenism and obtain a total testosterone, 17 hydroxyprogesterone or 17 OHP, dehydroepianosterone sulfate or DHEAS, and a pelvic ultrasound.
The testosterone and DHEAS may be elevated, and the 17 OHP will be normal. The pelvic ultrasound may show polycystic appearing ovaries, which is defined as 20 or more follicles measuring 2 to 9 millimeters in diameter or as an increased ovarian volume greater than 10 centimeters cubed on either ovary.

Functional Hypothalamic Amenorrhea 5:45–7:09

With these findings, you have the diagnosis of polycystic ovary syndrome or PCOS. Here's a clinical pearl.
Traditionally, PCOS is diagnosed based on clinical features like the Rotterdam criteria. The three criteria are ovulatory dysfunction such as irregular cycles, hyperandrogenism, and polycystic ovarian appearance on pelvic ultrasound.
If 2 out of the 3 Rotterdam criteria are met, then the diagnosis is PCOS. And now another high yield fact.
Patients with PCOS who have prolonged amenorrhea are at risk for endometrial intraepithelial neoplasia, also known as endometrial hyperplasia and endometrial carcinoma.
These patients have normal estrogen levels, but chronic anovulation and relatively low progesterone, which causes endometrial proliferation without shedding, leading to endometrial thickening, glandular crowding, and malignancy.
Now let's consider hypothalamic dysfunction. History might reveal weight loss, disordered eating, high performance exercise, chronic illness, or excess psychological stress.
Physical examination may reveal a body mass index of less than 20 vulval vaginal atrophy, and breast atrophy. The lab values will show normal TSH, normal prolactin, and low estradiol.

Hypothyroidism7:09–7:36

In this case, consider hypothalamic dysfunction and check FSH and LH levels. Also, perform a progestin challenge test, which involves prescribing oral medroxyprogesterone acetate to the patient for 5 to 10 days and monitoring for a withdrawal bleed.

Asherman syndrome 7:36–8:29

If the FSH is normal and LH is low, and there is no withdrawal bleeding after the progestin challenge, the diagnosis is functional hypothalamic amenorrhea.
Time for another clinical pearl. The female athlete's triad is a type of functional hypothalamic amenorrhea that was first diagnosed among competitive athletes and is defined by disordered eating, amenorrhea, and osteopenia or osteoporosis.
Consider bone density testing for all patients with amenorrhea who are exercising intensely and have disordered eating. Next, let's go over thyroid gland dysfunction.
These patients may report fatigue, lethargy, and cold intolerance. The pelvic examination is normal, while labs show elevated TSH, normal prolactin, and normal estradiol levels.

Pituitary adenoma8:29–10:02

At this point, you can consider thyroid gland dysfunction and obtain a free thyroxine or free T4 level. If it's low, the diagnosis is hypothyroidism.
Moving on, let's talk about anatomic obstruction. In this case, the history reveals prior intrauterine surgery and possibly cyclic pelvic pain or recurrent pregnancy loss.
The pelvic exam will be normal, but the cervical os might be stenotic. The TSH, prolactin, and estradiol levels are normal.
With these findings, consider anatomic obstruction and obtain a pelvic ultrasound. The ultrasound may show heterogeneous endometrial irregularity and endometrial fluid keeping with hemanometra, as well as bridging senechia.
The next step is to perform a diagnostic hysteroscopy and evaluate for intrauterine senechia or adhesions. If they are present, the diagnosis is Asherman syndrome.
So, let's move on to secondary amenorrhea with low FSH levels, generally less than 5, starting with pituitary gland tumors.
The patient may report headaches, impaired vision such as diplopia, decreased visual acuity or subjective visual field loss, and the presence of galactorrhea.
The physical examination may confirm visual field loss or diminished visual acuity, and the pelvic exam will be normal. The labs will demonstrate normal TSH and elevated prolactin.

Sheehan syndrome10:02–11:40

The estradiol level is usually low but may be normal or elevated. A prolactin level greater than 20 is abnormal, but suppression of menses does not usually occur until the prolactin is above 50.
With prolactin greater than 50, consider a pituitary tumor, repeat the prolactin level, and perform an MRI to see the ella tersica.
If the repeat prolactin is greater than 50 and the imaging demonstrates a pituitary mass, the diagnosis is a pituitary adenoma.
Here's one more high yield fact. Pituitary adenomas are classified by size.
Macroadenomas are greater than 10 millimeters, and microadenomas are less than 10 millimeters. Both types of masses can cause hyperprolactinemia, but the larger masses are more likely to cause headaches as well as visual changes due to compression of the optic chasm.
Finally, let's discuss anterior pituitary necrosis. These patients have a history of severe postpartum hemorrhage requiring a blood transfusion.
They also report the inability to lactate and may describe fatigue, constipation, cold intolerance, or vasomotor symptoms.
Symptoms are often mild and may not appear for several months or even years after childbirth. The physical exam findings might include weight loss and loss of axillary and pubic hair.

Assess for alternative diagnoses11:40–12:01

Labs may demonstrate a low TSH as well as a low prolactin and estradiol. With these findings, consider anterior pituitary necrosis.
Obtain a CBC, BMP, cortisol, and growth hormone levels, as well as an MRI of the cellaturica. The lab results may demonstrate anemia, hyponatremia, and hypoglycemia, which are indicators of adrenal insufficiency, as well as low cortisol and low growth hormone levels.

Review12:01–13:42

The MRI may demonstrate an empty cella or small pituitary gland, confirming that the diagnosis is Sheehan's syndrome. Let's take a break with a clinical pearl.
Due to advances in obstetrical care, Sheehan's syndrome has become less common. However, any patient with severe postpartum hemorrhage should be evaluated for adrenal insufficiency immediately postpartum and assessed for other signs of hypopituitarism in the following 4 to 6 weeks.
After considering and assessing for these causes of secondary amenorrhea, consider and assess for alternative diagnoses.
These include androgen secreting tumor, non-classical congenital adrenal hyperplasia, Lactational amenorrhea, hormonal contraceptives, and menopause.
Alright, as a quick recap, secondary amenorrhea is defined as the absence of menses for 3 months in a patient with a history of regular menses or 6 months in a patient with a history of irregular cycles.
Common causes include primary ovarian insufficiency, PCOS functional hypothalamic amenorrhea, and hyperprolactinemia as seen with a pituitary adenoma.
Other causes include hypothyroidism, Asherman syndrome, and Sheehan syndrome.