Dr Kokila Das
Keya Fertility
embryoedu internationale
Bhubaneswar,Odisha
• Prolactin (PRL) is a polypeptide protein
hormone secreted by the lactotroph cells in the
anterior pituitary gland .
• Suppressed by hypothalamic dopamine to act
on Lactotroph D2 receptors .
• Prolactin (PRL) is the hormone act as
stimulation & maintenance of milk production
in the breast .
• Most common functional pituitary adenomas .
• Prolactinoma account for 40 % of pituitary
tumor
• Microprolactinomas are more frequent in
women.
• Macroprolactinomas are more frequent in men.
• Gender : femal more than male 10 :1
• Age : 20-50 years .
• Some growth hormone producing tumors also
cosecrete PRL
Incidence of hyperprolactinemia
 Unselected healthy adult : 0.4 % - 5.0 %
 Among women with Amenorrhea : 9%
 Among women with galactorrhea : 25%
 Among women with amenorrhea and
galactorrhea : 70%
 Among men with impotence or infertility : 5%
 Hyperprolactinaemia is the most common
disorder of the hypothalamo-pituitary axis.
 Prolactinomas are the most common hormone-
secreting pituitary tumours.
 Rarely life-threatening
 symptoms primarily as a result of
hyperprolactinaemia are alteration in
reproductive/sexual function & symptoms
owing to mass effects.
Hyperprolactinemia can be defined as the
presence of abnormally high level of prolactin
in the blood.
Normal levels are typically 10–35 ng/ml
( 1 ng is equivalent to 21.2 mU/ml )
A prolactinoma should be suspected if the
serum prolactin is ≥100 ng/ml.
The goals of treatment are
- normalise prolactin levels
- restore gonadal function
- reduce the effects of chronic
hyperprolactinaemia.
Hormonal Effect :
• Women : infertility, oligomenorrhea,
amenorrhea or rarely galactorrhea .
• Men : decreased libido, impotence, infertility,
gynecomastia, or rarely galactorrhea
• Mass Effect : headache ,CSF rhinorrhea ,
compression of optic chiasma & cranial nerve .
 The primary action of prolactin is to stimulate
lactation, but it is the effect of prolactin on
gonadal function that warrants clinical
attention.
 Hypersecretion of prolactin leads to infertility
and gonadal dysfunction by interrupting
secretion of gonadotropin-releasing hormone
inhibiting the release of LH and FSH , and
impairing gonadal steroidogenesis .
 Prolactin inhibits oestrogen synthesis in the
ovary
 In 20% of cases of secondary amenorrhoea,
hyperprolactinaemia prevents ovulation by
impairing normal follicular development
 Diagnosis by symptoms and lab test/MRI
 Differentiate physiological & pathological
causes
 Identify the size micro/macroadenoma
 Apply specific pharmacotherapy treatment
 A single measurement of serum prolactin level
can confirm the diagnosis if the level is above
the upper limit of normal
 Macroprolactin evaluation is recommended in
patients with asymptomatic
hyperprolactinemia.
When there is a discrepancy between a very
large pituitary tumour and a mildly elevated
prolactin level, serial dilution of serum samples
is recommended to eliminate the "hook effect,"
or an artifact that can occur with some
immunoradiometric assays leading to a falsely
low prolactin value.
The indications for treatment
1) Neurologic symptoms
2) Hypogonadism
3) Infertility
* The corner stone treatment of prolactinomas are
medical treatment .
1) DOPAMINE AGONISTS
 Dopamine agonists decrease prolactin secretion
and reduce the size of the lactotroph adenoma
in more than 90 % of patients.
 Decrease symptoms within days .
 Decrease in serum prolactin within 2-3 weeks
 Decrease in size within 6 weeks
DOPAMINE AGONISTS
 Bromocriptine : It was given at least twice a
day . 1.25 -2.5 mg PO at bedtime or with
dinner. ( max. 15 mg / d )
 Cabergoline : administered once or twice a
week . 0.25 mg twice /wk or 0.5 mg once/wk
2)TRANSSPHENOIDAL SURGERY
* The indications for surgery :
1) Patients who do not respond to medical
treatment or those who show progression after
an initial response to medical treatment
2) Women who have a microadenoma, desire
pregnancy, and cannot tolerate medical
treatment.
 3) RADIATION THERAPY
* The indications for radiation : radiation is
primarily used to prevent regrowth of residual
tumor in a patient with a very large
macroadenoma after transsphenoidal
debulking .
4) ORAL CONTRACEPTIVE
* The indications for Estrogen- progestin : can be
considered as therapy in women with
symptomatic microprolactinomas IF :
women cannot tolerate
do not respond to dopamine agonists
do not want to become pregnant.
 * After one month of therapy, the patient
should be evaluated for side effects and serum
prolactin should be measured , So:
 If the serum PRL is normal and no S/E So,
(continued).
 If the serum PRL not decreased to normal but
no S/E , the dose should be increased
gradually to as much as 1.5 mg of Cabergoline
2 or 3 times / week or 5 mg of Bromocriptine 2
times / day.
 Whatever dose results in a normal serum
prolactin value should be continued
 If the prolactin has been normal for two or
more years and no adenoma is seen on MRI So,
discontinuation of the drug
Recommendations for pregnant women with
prolactinoma
Specific recommendations for management of
prolactinoma during pregnancy are as
follows (Melmed 2011):
 Women with prolactinomas should discontinue
dopamine agonist therapy as soon as
pregnancy is recognized, except for selected
patients with invasive macroadenomas or
adenomas abutting the optic chiasm.
 Serum prolactin measurements should not be
performed during pregnancy.
 Unless there is clinical evidence for tumour
growth, such as visual field impairment,
routine use of pituitary MRI during pregnancy
is not recommended in patients with
microadenomas or intrasellar macroadenomas.
 Pregnant women with prolactinomas who
experience severe headaches and/or visual
field changes should have formal visual field
assessment followed by MRI without
gadolinium.
 Bromocriptine therapy is recommended in
patients who experience symptomatic growth
of a prolactinoma during pregnancy.
 As reproductive clinicians, it is important that
the pathological relevance of
hyperprolactinemia is established before
commencing treatment for this
endocrinological disorder.
 Most cases of true hyperprolactinemia are
associated with amenorrhea or hormone
deprivation in premenopausal women and can
be managed by dopamine agonist or hormone
replacement therapy respectively.
Hyperprolactinemia

Hyperprolactinemia

  • 1.
    Dr Kokila Das KeyaFertility embryoedu internationale Bhubaneswar,Odisha
  • 2.
    • Prolactin (PRL)is a polypeptide protein hormone secreted by the lactotroph cells in the anterior pituitary gland . • Suppressed by hypothalamic dopamine to act on Lactotroph D2 receptors . • Prolactin (PRL) is the hormone act as stimulation & maintenance of milk production in the breast .
  • 4.
    • Most commonfunctional pituitary adenomas . • Prolactinoma account for 40 % of pituitary tumor • Microprolactinomas are more frequent in women. • Macroprolactinomas are more frequent in men. • Gender : femal more than male 10 :1 • Age : 20-50 years . • Some growth hormone producing tumors also cosecrete PRL
  • 5.
    Incidence of hyperprolactinemia Unselected healthy adult : 0.4 % - 5.0 %  Among women with Amenorrhea : 9%  Among women with galactorrhea : 25%  Among women with amenorrhea and galactorrhea : 70%  Among men with impotence or infertility : 5%
  • 6.
     Hyperprolactinaemia isthe most common disorder of the hypothalamo-pituitary axis.  Prolactinomas are the most common hormone- secreting pituitary tumours.  Rarely life-threatening  symptoms primarily as a result of hyperprolactinaemia are alteration in reproductive/sexual function & symptoms owing to mass effects.
  • 7.
    Hyperprolactinemia can bedefined as the presence of abnormally high level of prolactin in the blood. Normal levels are typically 10–35 ng/ml ( 1 ng is equivalent to 21.2 mU/ml ) A prolactinoma should be suspected if the serum prolactin is ≥100 ng/ml.
  • 10.
    The goals oftreatment are - normalise prolactin levels - restore gonadal function - reduce the effects of chronic hyperprolactinaemia.
  • 12.
    Hormonal Effect : •Women : infertility, oligomenorrhea, amenorrhea or rarely galactorrhea . • Men : decreased libido, impotence, infertility, gynecomastia, or rarely galactorrhea • Mass Effect : headache ,CSF rhinorrhea , compression of optic chiasma & cranial nerve .
  • 13.
     The primaryaction of prolactin is to stimulate lactation, but it is the effect of prolactin on gonadal function that warrants clinical attention.  Hypersecretion of prolactin leads to infertility and gonadal dysfunction by interrupting secretion of gonadotropin-releasing hormone inhibiting the release of LH and FSH , and impairing gonadal steroidogenesis .
  • 14.
     Prolactin inhibitsoestrogen synthesis in the ovary  In 20% of cases of secondary amenorrhoea, hyperprolactinaemia prevents ovulation by impairing normal follicular development
  • 16.
     Diagnosis bysymptoms and lab test/MRI  Differentiate physiological & pathological causes  Identify the size micro/macroadenoma  Apply specific pharmacotherapy treatment
  • 17.
     A singlemeasurement of serum prolactin level can confirm the diagnosis if the level is above the upper limit of normal  Macroprolactin evaluation is recommended in patients with asymptomatic hyperprolactinemia.
  • 18.
    When there isa discrepancy between a very large pituitary tumour and a mildly elevated prolactin level, serial dilution of serum samples is recommended to eliminate the "hook effect," or an artifact that can occur with some immunoradiometric assays leading to a falsely low prolactin value.
  • 19.
    The indications fortreatment 1) Neurologic symptoms 2) Hypogonadism 3) Infertility * The corner stone treatment of prolactinomas are medical treatment .
  • 20.
    1) DOPAMINE AGONISTS Dopamine agonists decrease prolactin secretion and reduce the size of the lactotroph adenoma in more than 90 % of patients.  Decrease symptoms within days .  Decrease in serum prolactin within 2-3 weeks  Decrease in size within 6 weeks
  • 21.
    DOPAMINE AGONISTS  Bromocriptine: It was given at least twice a day . 1.25 -2.5 mg PO at bedtime or with dinner. ( max. 15 mg / d )  Cabergoline : administered once or twice a week . 0.25 mg twice /wk or 0.5 mg once/wk
  • 23.
    2)TRANSSPHENOIDAL SURGERY * Theindications for surgery : 1) Patients who do not respond to medical treatment or those who show progression after an initial response to medical treatment 2) Women who have a microadenoma, desire pregnancy, and cannot tolerate medical treatment.
  • 24.
     3) RADIATIONTHERAPY * The indications for radiation : radiation is primarily used to prevent regrowth of residual tumor in a patient with a very large macroadenoma after transsphenoidal debulking .
  • 25.
    4) ORAL CONTRACEPTIVE *The indications for Estrogen- progestin : can be considered as therapy in women with symptomatic microprolactinomas IF : women cannot tolerate do not respond to dopamine agonists do not want to become pregnant.
  • 26.
     * Afterone month of therapy, the patient should be evaluated for side effects and serum prolactin should be measured , So:  If the serum PRL is normal and no S/E So, (continued).  If the serum PRL not decreased to normal but no S/E , the dose should be increased gradually to as much as 1.5 mg of Cabergoline 2 or 3 times / week or 5 mg of Bromocriptine 2 times / day.
  • 27.
     Whatever doseresults in a normal serum prolactin value should be continued  If the prolactin has been normal for two or more years and no adenoma is seen on MRI So, discontinuation of the drug
  • 28.
    Recommendations for pregnantwomen with prolactinoma Specific recommendations for management of prolactinoma during pregnancy are as follows (Melmed 2011):  Women with prolactinomas should discontinue dopamine agonist therapy as soon as pregnancy is recognized, except for selected patients with invasive macroadenomas or adenomas abutting the optic chiasm.
  • 29.
     Serum prolactinmeasurements should not be performed during pregnancy.  Unless there is clinical evidence for tumour growth, such as visual field impairment, routine use of pituitary MRI during pregnancy is not recommended in patients with microadenomas or intrasellar macroadenomas.
  • 30.
     Pregnant womenwith prolactinomas who experience severe headaches and/or visual field changes should have formal visual field assessment followed by MRI without gadolinium.  Bromocriptine therapy is recommended in patients who experience symptomatic growth of a prolactinoma during pregnancy.
  • 31.
     As reproductiveclinicians, it is important that the pathological relevance of hyperprolactinemia is established before commencing treatment for this endocrinological disorder.  Most cases of true hyperprolactinemia are associated with amenorrhea or hormone deprivation in premenopausal women and can be managed by dopamine agonist or hormone replacement therapy respectively.