Endocrine 08 Part 4

Front 1

Describe the significance of menstrual cycles of irregular length or lack of cycles (amenorrhea)

Back 1

Indicates disturbances along the hypothalamic-pituitary-ovarian axis

Front 2

If a patient is having menstrual cycle problems what sort of therapy is in order if the patient wishes to conceive?

Back 2

Ovulation induction therapy

Front 3

Describe the procedure for induction of ovulation

Back 3

1. Measure FSH concentrations to rule out patients with premature ovarian failure. MIS can also be measured

2. Measure prolactin concentrations to rule out hyperprolactinemia

3. Perform a progesterone withdrawal test to determine whether the patient is secreting estrogen or whether she is hypoestrogenic

Front 4

Describe the significance of elevated FSH levels in a patient trying to conceive

Back 4

If FSH levels are elevated, as at menopause, end organ (ovarian) failure is present and ovulation induction therapy will be ineffective

Front 5

Describe what must be done in a patient with ovarian failure if pregnancy is desired

Back 5

Assisted reproductive technology, such as the use of an oocyte donor is required

Front 6

Describe the significance of MIS (mullerian inhibiting substance) for the induction of ovulation

Back 6

-MIS concentrations may also be measured
-Low levels suggest a decrease in the overall pool of recruitable follicles

Front 7

Describe the consequences of high levels of prolactin for the induction of ovulation

Back 7

High levels of prolactin are known to interfere with normal gonadotropin secretion and the menstrual cycle (the galactorrhea-amenorrhea syndrome).

Front 8

Describe the action of GnRH when delivered in a pulsatile fashion

Back 8

1. Stimulates the release of both FSH and LH
2. If administered with the proper frequency and amplitude, gonadotropin release will stimulate recruitment of folliclces and folliculogenesis

Front 9

How is progress of folliculogenesis monitored in patients when receiving GnRH?

Back 9

Blood estradiol levels and timed ultrasonography

Front 10

What is the indication for use of GnRH therapy?

Back 10

To induce ovulation

Front 11

When is ovulation therapy with GnRH most successful?

Back 11

In patients with an ovulatory defect resulting from deficient GnRH secretion, such as patients with hypogonadotropic hypogonadism
-This includes women with primary GnRH deficiency (Kallman's syndrome)
-Also includes women with an intact hypothalamus but decreased GnRH release (hypothalamic amenorrhea)

Front 12

Describe how to identify patients with an intact hypothalamus but decreased GnRH release (hypothalamic amenorrhea)

Back 12

These patients are hypoestrogenic so the progesterone withdrawal test (no withdrawal bleeding) will readily identify them

Front 13

Describe the side effects of GnRH therapy

Back 13

1. Few side effects have been reported
2. Ovarian hyperstimulation and multiple folliculogenesis (somtimes observed after gonadotropin therapy) do not occur
3. This is probably because inhibitory estradiol feedback mechanisms can still exert some degree of control on pituitary gonadotropin secretion

Front 14

Describe the mode of action of LH and FSH

Back 14

1. Will induce the recruitment and maturation of a new pool of follicles and promote estradiol secretion

Front 15

Describe the two step procedure of gonadotropin therapy

Back 15

1. Obtain follicular maturation
2. After follicular maturation has been obtained, ovulation is induced by a luteinizing agent (LH or hCG)

Timing of the second step, which mimics the midcycle gonadotropin surge, must be precise. Therefore, progression of the follicular maturation process must be monitored carefully

Front 16

What is gonadotropin therapy used for?

Back 16

To induce ovulation

Front 17

Who are the ideal candidates for gonadotropin therapy?

Back 17

Hypogonadotropic patients

Front 18

Who can be a candidate for gonadotropin therapy?

Back 18

-Hypogonadotropic patients
-Normogonadotropic patients
-Oligo-ovulatory patients

Front 19

What must be monitored in patients receiving gonadotropin therapy?

Back 19

Patients must be monitored carefully to determine the number of follicles which have been recruited and the follicular maturation process

Front 20

How do you avoid complications in gonadotropin therapy?

Back 20

Frequent estradiol measurements and ultrasound sessions are required to determine the precise time for the ovulatory stimulus and to avoid complications

Front 21

How do you determine the precise time for the ovulatory stimulus in gonadotropin therapy?

Back 21

Frequent estradiol measurements and ultrasound sessions are required to determine the precise time for the ovulatory stimulus and to avoid complications

Front 22

Describe the toxic effects from gonadotropin therapy

Back 22

None except for occasional mile febrile reactions

Front 23

What are the potentially major complications of gonadotropin therapy?

Back 23

1. Multiple gestations
2. Ovarian hyperstimulation

Front 24

Describe multiple gestations from gonadotropin therapy

Back 24

The physiological mechanisms that account for the selection of a single follicle in the normal cycle are overtaken and multiple follicles are recruited and mature, leading to multiple ovulations

Front 25

Describe ovarian hyperstimulation from gonadotropin therapy

Back 25

1. Normal endogenous estradiol negative feedback mechanisms which physiologically control endogenous GnRH and gonadotropin release and thus the degree of ovarian stimulation are overruled by the massive exogenous gonadotropin treatment
2. This full-blown hyperstimulation includes massive enlargement of the ovaries, ascites, and hydrothorax

Front 26

Describe how to prevent ovarian hyperstimulation from gonadotropin therapy

Back 26

1. Careful monitoring of follicular maturation

2. Gonadotropin treatment should not be undertaken without the facilities for estrogen measurement and ultrasound monitoring of follicular growth

Front 27

Describe withholding the hCG injection

Back 27

1. May have to if estradiol levels are too elevated or if the number of stimulated follicles is too high

2. Withholding hCG can prevent the ovarian hyperstimulation syndrome

Front 28

Why are hCG injections withheld if estradiol levels are too high?

Back 28

This hormone has a long half-life and results in a sustained leteotropic effect and supraphysiological levels of estrogens and progesterone, aggravating the hyperstimulation

Front 29

When is adjunctive treatment with a GnRH antagonist indicated in gonadotropin therapy?

Back 29

To prevent premature luteinization of the recruited follicles

Front 30

Describe premature endogenous LH surges in response to the rising estradiol in cases of ovarian stimulation

Back 30

1. Occurs in 20% of cases of ovarian stimulation
2. The LH surge is premature because the follicles have, at that time, not attained full maturity and results in a luteinization of the follicles

Front 31

What has premature luteinization been associated with?

Back 31

Poor fertilization rate and lower fecundity

Front 32

Describe the mode of action of Clomiphene

Back 32

1. Binds to high-affinity estradiol receptors and acts as a competitive inhibitor of estradiol in several tissues
2. Through competitive binding to hypothalamic and pituitary estradiol receptors, clomiphene acts primarily as an antiestrogen by preventing endogenous estradiol from exerting its effects and blocking the negative feedback loop of endogenous estrogens
3. This results in an increase in FSH and LH

Front 33

Describe what occurs as a result of the increase in FSH and LH from Clomiphene

Back 33

There is a recruitment of a new pool of follicles and a new follicular phase begins:
a. There is follicular growth
b. There is an increase in endogenous estrogens
c. Selection of a dominant follicle
d. Activation of the estradiol positive feedback loop and ovulation

Front 34

What is Clomiphene used for?

Back 34

To induce ovulation

Front 35

In whom is Clomiphene NOT effective?

Back 35

Patients lacking endogenous estrogen production

Front 36

Who are candidates for Clomiphene therapy?

Back 36

Oligo-ovulatory and amenorrheic women with evidence of endogenous estrogenic activity

Front 37

How is clomiphene administered?

Back 37

Orally, beginning on the 3rd-5th day of the menstrual cycle for 5 days

Front 38

How are the follicular response and the ovulatory response assessed in Clomiphene therapy?

Back 38

Follicular Response: Estradiol measurements and ultasonography of the ovary

Ovulatory response: The measurement of LH and progesterone

Front 39

Describe the side effects of Clomiphene therapy

Back 39

-Ovarian enlargment
-Vasomotor flushes
-Lower abdominal pain and discomfort
-Nausea
-Breast tenderness
-Visual symptoms (blurred vision) at higher dosease