Fircracker - Amenorrhea and PCOS

Question 1

What causes of secondary amenorrhea can be treated with behaviour modification?

Answer 1

Behaviour modification should be considered for patients that have amenorrhea due to eating disorders or exercise

Question 2

If pregnancy has been ruled out, what is the next step in the diagnosis of primary amenorrhea?

Answer 2

In the diagnosis of primary amenorrhea, if pregnancy has been ruled out then look for secondary sexual characteristics.

If secondary sexual characteristics are present, perform a physical exam and ultrasound to look for anatomical abnormalities and a genetic analysis for XY genotype (androgen insensitivity).

If secondary sexual characteristics are not present, check FSH and LH.

If FSH and LH are high, suspect gonadal agenesis, gonadal dysgenesis, or ovarian failure.

If FSH and LH are low, check prolactin.

If prolactin is high, suspect prolactinoma. If prolactin is normal suspect GnRH deficiency or another hypothalamic-pituitary dysfunction.

Question 3

How should secondary amenorrhea as a result of Asherman syndrome be treated?

Answer 3

Asherman syndrome can be treated with estrogen and lysis of adhesions

Question 4

What anatomic abnormalities can result in primary amenorrhea?

Answer 4

Anatomic abnormalities include:

Mullerian agenesis (such as blind ending vagina)

Imperforate hymen

Transverse vaginal septum

Question 5

What are the treatment strategies and treatments of primary amenorrhea?

Answer 5

Treatment of primary amenorrhea should include menarche, or treat factors preventing menarche:

• Constitutional growth delay requires no treatment
• Anatomic abnormalities may require surgical intervention
• Hypogonadism/ovarian failure can be treated with hormone replacement with low dose estrogen

Question 6

What is secondary amenorrhea?

Answer 6

Secondary amenorrhea is defined as 6 months without menses in a woman who has passed menarche. Note: While some sources only require 3 months without menses to diagnose amenorrhea, the American College of Obstetricians and Gynecologists uses the definition above.

Question 7

How should secondary amenorrhea as a result of premature ovarian failure be treated?

Answer 7

Premature ovarian failure should be treated with estrogen and progesterone replacement.

Question 8

What are the main principles underlying treatment of secondary amenorrhea?

Answer 8

Treatment of secondary amenorrhea is to address the underlying cause of amenorrhea.

Hypothalamic-pituitary dysfunction should be treated with GnRH or gonadotropin replacement.

Premature ovarian failure should be treated with estrogen and progesterone replacement.

Prolcatinomas should be treated with surgical removal or with dopamine agonists.

Behavior modification should be considered for patients that have amenorrhea due to eating disorders or exercise

Asherman syndrome can be treated with estrogen and lysis of adhesions.

Thyroid dysfunction and Cushing causing amenorrhea should be treated according to the specific pathology.

Question 9

What are the various treatment strategies available for polycystic ovarian syndrome?

Answer 9

Exercise and weight loss are recommended for patients with PCOS to address insulin resistance and associated obesity.

Oral contraceptives and continuous progestins such as the mirena IUD and nexplanon implant can be used to decrease endometrial proliferation and, thus, decrease the risk of endometrial cancer. ALL patients with PCOS who are not currently trying to conceive should be treated with oral contraceptives or continuous progestins.

Progestin alone for 7 days each month can induce bleeding and prevent endometrial hyperplasia.

Spironolactone has antiandrogen effects, which can be used to treat hirsutism if oral contraceptives alone do not resolve the symptoms. Note: spironolactone must be stopped during pregnancy due to the risk of antiandrogenic effects in a male fetus.

Clomiphene is an antiestrogen, which will induce follicle stimulation by preventing negative feedback of estrogen on FSH. This allows follicle maturation to allow pregnancy to occur. Femara is also used.

Metformin can help facilitate weight loss, improve cholesterol, reduce blood pressure, and reduce cardiovascular risk in patients with insulin resistance. Some women have shown to start ovulating with the use of metformin alone.

Statins can be considered if lipids and testosterone levels need to be lowered.

Antibiotics can be used to treat acne associated with PCOS.

Question 10

What causes of primary amenorrhea should be suspected based on prolactin levels?

Answer 10

If prolatin level is high, suspect prolactinoma, if prolactin is normal suspect GnRH deficiency or another hypothalamic-pituitary dysfunction

Question 11

What is the role of insulin in polycystic ovarian syndrome?

Answer 11

In patients with PCOS, the ovaries are hypersensitive to insulin, insulin stimulates the ovarian theca cells to secrete androgens while inhibiting hepatic sex hormone binding globulin. The result is increased free androgens.

Question 12

In the diagnosis of primary amenorrhea, what lab study should be performed next if secondary sexual characteristics are not present?

Answer 12

If secondary sexual characteristics are not present, check FSH and LH.

Question 13

What is the comprehensive diagnostic strategy for determining a cause for secondary amenorrhea?

Answer 13

In the diagnosis of secondary amenorrhea, if pregnancy has been ruled out then check thyroid function.

If thyroid function is abnormal, suspect thyroid dysfunction. If thyroid function is normal,check prolactin.

If prolactin is high, suspect prolactinoma. If prolactin is normal, perform a progestin challenge.

If progestin challenge in positive (bleeding upon withdrawal of progestin), check forhirsutism.

If hirsutism is present in a patient with secondary amenorrhea and a positive progestin challenge, suspect polycystic ovarian syndrome, ovarian or adrenal tumor, or cushing syndrome.

If hirsutism is not present in a patient with secondary amenorrhea and a positive progestin challenge, suspect anorexia, exercise, stress, of hypothalamic pituitary dysfunction.

If progestin challenge is negative, administer estrogen-progesterone challenge.
If the estrogen-progesterone challenge is negative, suspect Asherman syndrome(intrauterine adhesions, usually resulting from excessively vigorous instrumentation of the uterus). Remember that, while Asherman syndrome is described as a complication of dilation and curettage procedures (D&Cs), Asherman syndrome is rare even in patients who have undergone multiple D&Cs.

If an estrogen-progesterone challenge is positive, check FSH and LH.
If FSH and LH are high, suspect ovarian failure. If low, suspect hypothalamic-pituitary dysfunction.

Question 14

What is the diagnostic criteria for polycystic ovarian syndrome?

Answer 14

Diagnosis of polycystic ovarian syndrome requires at least two of the following of the Rotterdam criteria:

• Anovulation
• Excessive androgens
• Polycystic ovaries (12 or more cysts per ovary)

Laboratory findings associated with PCOS include:

• Classically LH:FSH ratio greater than 3 but often just LH>FSH
• Increased DHEA
• Increased androstenedione
• Positive progestin challenge

It is important to note that 17-OH progesterone is normal and can be used to differentiate from atypical congenital adrenal hyperplasia which presents with similar clinical symptoms in young adult females.

Ultrasound findings associated with PCOS include enlarged ovaries with 12 or more follices per ovary.

Question 15

What is complete androgen insensitivity?

Answer 15

In complete androgen insensitivity patients are genetically male and have testes, but lack testosterone receptors. Testosterone is converted to estrogen, leading to breast development. These patients lack pubic hair and have no uterus.

Question 16

In the diagnosis of secondary amenorrhea, what lab study should be performed next if an estrogen-progesterone challenge is positive?

Answer 16

If an estrogen-progesterone challenge is positive, check FSH and LH

Question 17

What is the role of spironolactone in the treatment of polycystic ovarian syndrome?

Answer 17

Spironolactone has antiandrogen effects, which can be used to treat hirsutism if oral contraceptives alone do not resolve the symptoms. Note: spironolactone must be stopped during pregnancy due to the risk of antiandrogenic effects in a male fetus.

Question 18

How should secondary amenorrhea as a result of hypothalamic-pituitary dysfunction be treated?

Answer 18

Hypothalamic-pituitary dysfunction should be treated with GnRH or gonadotropin replacement.

Question 19

In the diagnosis of secondary amenorrhea, what pathologies should be suspected if a progestin challenge is positive and hirsutism is present?

Answer 19

If hirsutism is present in a patient with secondary amenorrhea and a positive progestin challenge, suspect polycystic ovarian syndrome, ovarian or adrenal tumor, or cushing syndrome.

Question 20

What causes of primary amenorrhea should be suspected if FSH and LH are high?

Answer 20

If FSH and LH are high, suspect gonadal agenesis, gonadal dysgenesis, or ovarian failure.

Question 21

What is the classical clinical presentation and examination findings (on bimanual examination) of a patient with PCOS?

Answer 21

The classic presentation of polycystic ovarian syndrome is an overweight young woman presenting with:

Oligomenorrhea
Hirsutism
Virilism
Infertility
Acne
Insulin resistance (seen in 50-70% of women with PCOS)

Decreased FSH leads to follicular degeneration with fluid-filled cyst formation (hencepolycystic). Bilateral ovarian enlargement may be found on bimanual examination.
Menstrual dysfunction due to PCOS manifests as amenorrhea, oligomenorrhea, and breakthrough bleeding, which are all the result of anovulation.

Question 22

In the diagnosis of secondary amenorrhea, what study should be performed next if pregnancy test is negative and thyroid function is normal?

Answer 22

If thyroid function is abnormal, suspect thyroid dysfunction. If thyroid function is normal,check prolactin.

Question 23

What is polycystic ovarian syndrome?

Answer 23

Polycystic Ovarian Syndrome (PCOS), also known as Stein-Leventhal syndrome, is a hypothalamic-pituitary disease that results in enlarged, polycystic ovaries and chronic anovulation, which leads to elevated estrogen and androgen production and atypical follicle development.

Question 24

What is the role of clomiphene in the treatment of polycystic ovarian syndrome?

Answer 24

Clomiphene is an antiestrogen, which will induce follicle stimulation by preventing negative feedback of estrogen on FSH. This allows follicle maturation to allow pregnancy to occur. Femara is also used.

Question 25

What is the presentation of menstrual dysfunction that results from polycystic ovarian syndrome?

Answer 25

Menstrual dysfunction due to PCOS manifests as amenorrhea, oligomenorrhea, and breakthrough bleeding, which are all the result of anovulation.

Question 26

What causes polycystic ovarian syndrome?

Answer 26

The pathogenesis is poorly understood. It is thought that high amplitude GnRH pulses, cause increased pituitary LH leading to ovarian (theca interna) androgen synthesis and increased androgen aromatization to estrogens in adipose tissue.

Question 27

What are some complications of polycystic ovarian syndrome?

Answer 27

Complications of PCOS include:

Increased risk of endometrial and breast cancer, due to increased estrogen
Infertility due to anovulation
Increased risk of diabetes mellitus type II
Hypertension and ischemic heart disease because of the high prevalence of obesity and insulin resistance
Ovarian torsion because of enlarged ovaries

Question 28

If pregnancy has been ruled out, what is the next step in the diagnosis of secondary amenorrhea?

Answer 28

In the diagnosis of secondary amenorrhea, if pregnancy has been ruled out then checkthyroid function.

Question 29

What is the role of oral contraceptives and continuous progestins in the treatment of polycystic ovarian syndrome?

Answer 29

Oral contraceptives and continuous progestins such as the mirena IUD and nexplanon implant can be used to decrease endometrial proliferation and, thus, decrease the risk of endometrial cancer. ALL patients with PCOS who are not currently trying to conceive should be treated with oral contraceptives or continuous progestins.

Question 30

What diagnosis is suggested by elevated FSH and LH in a patient with secondary amenorrhea? What should be suspected if FSH and LH are low?

Answer 30

If FSH and LH are high, suspect ovarian failure. If low, suspect hypothalamic-pituitary dysfunction.

Question 31

If an estrogen-progesterone challenge is negative, what cause of secondary amenorrhea should be suspected?

Answer 31

If the estrogen-progesterone challenge is negative, suspect Asherman syndrome(intrauterine adhesions, usually resulting from excessively vigorous instrumentation of the uterus). Remember that, while Asherman syndrome is described as a complication of dilation and curettage procedures (D&Cs), Asherman syndrome is rare even in patients who have undergone multiple D&Cs.

Question 32

What causes of primary amenorrhea should be suspected if secondary sexual characteristics are present?

Answer 32

If secondary sexual characteristics are present, perform a physical exam and ultrasound to look for anatomical abnormalities and a genetic analysis for XY genotype (androgen insensitivity).

Question 33

What laboratory findings are associated with polycystic ovarian syndrome?

Answer 33

Laboratory findings associated with PCOS include:

Classically LH:FSH ratio > 3, but often just LH > FSH
Increased DHEA
Increased androstenedione
Positive progestin challenge

It is important to note that 17-OH progesterone is normal, and can be used to differentiate from atypical congenital adrenal hyperplasia, which presents with similar clinical symptoms in young adult females.

Question 34

In the diagnosis of secondary amenorrhea, what study should be performed next if pregnancy test is negative, and TSH and prolactin levels are normal?

Answer 34

If prolactin is high, suspect prolactinoma. If prolactin is normal, perform a progestin challenge.

If progestin challenge in positive (bleeding upon withdrawal of progestin), check forhirsutism.

Question 35

What is the role of cyclic progestin in the treatment of polycystic ovarian syndrome?

Answer 35

Progestin alone for 7 days each month can induce bleeding and prevent endometrial hyperplasia.

Question 36

What is primary amenorrhea?

Answer 36

Primary amenorrhea is defined as the absence of menses by age 16 in a patient with secondary sexual characteristics, or absence of both menses and secondary sexual characteristics by age 13.

Absence of secondary sexual characteristics indicates a lack of estrogen. Causes of inadequate estrogen include:

Constitutional growth delay
Ovarian insufficiency
Turner Syndrome
Central hypogonadism (caused by malnutrition, prolactinoma, stress)

Question 37

In the diagnosis of secondary amenorrhea, what study should be performed next if a progestin challenge is negative?

Answer 37

If progestin challenge is negative, administer estrogen-progesterone challenge.

Question 38

What is the comprehensive diagnostic strategy for determining a cause of secondary amenorrhea?

Answer 38

In the diagnosis of secondary amenorrhea, if pregnancy has been ruled out then checkthyroid function.

If thyroid function is abnormal, suspect thyroid dysfunction. If thyroid function is normal,check prolactin.

If prolactin is high, suspect prolactinoma. If prolactin is normal, perform a progestin challenge.

If progestin challenge in positive (bleeding upon withdrawal of progestin), check forhirsutism.

If hirsutism is present in a patient with secondary amenorrhea and a positive progestin challenge, suspect polycystic ovarian syndrome, ovarian or adrenal tumor, or cushing syndrome.

If hirsutism is not present in a patient with secondary amenorrhea and a positive progestin challenge, suspect anorexia, exercise, stress, of hypothalamic pituitary dysfunction.

If progestin challenge is negative, administer estrogen-progesterone challenge.
If the estrogen-progesterone challenge is negative, suspect Asherman syndrome(intrauterine adhesions, usually resulting from excessively vigorous instrumentation of the uterus). Remember that, while Asherman syndrome is described as a complication of dilation and curettage procedures (D&Cs), Asherman syndrome is rare even in patients who have undergone multiple D&Cs.

If an estrogen-progesterone challenge is positive, check FSH and LH.
If FSH and LH are high, suspect ovarian failure. If low, suspect hypothalamic-pituitary dysfunction.

Question 39

What does the presence of secondary sexual characteristics, but no menses by age 16 suggest about hypothalamic-pituitary-ovarian function?

Answer 39

Patients with normal secondary sexual characteristics but no menses by age 16 have normal estrogen, indicating normal hypothalamic-pituitary-ovarian function, but a problem elsewhere.

Anatomic abnormalities include Mullerian agenesis (such as a blind-ending vagina), an imperforate hymen, or transverse vaginal septum.
In complete androgen insensitivity patients are genetically male and have testes, but lack testosterone receptors. Testosterone is converted to estrogen, leading to breast development. These patients lack pubic hair and have no uterus.