Prolactin enhances breast development during pregnancy and induces lactation. It is produced in the pituitary gland and its levels are normally inhibited by dopamine. Prolactin levels may be elevated in conditions like prolactinomas or certain drugs. Hyperprolactinemia can cause symptoms like menstrual irregularities, infertility, and galactorrhea. Prolactinomas are treated initially with dopamine agonists like cabergoline, which lower prolactin levels by activating D2 receptors on lactotroph cells. Cabergoline is more potent and long-acting than bromocriptine, making it a preferred treatment for conditions involving elevated prolactin levels.

2. ProlactinProlactin
Enhances breast development during
pregnancy, induces lactation & binds to specific
receptors in the gonads
Secretion is under tonic inhibitory control of
dopamine, which acts via D2 receptors located
on lactotrophs
Production can be stimulated by thyrotropin-releasing hormone
(TRH) and vasoactive intestinal peptide (VIP)
Normal level in women: less than 500 mIU/L (20 ng/ml or µg/l)
Prolactin is down regulated by dopamine and is up regulated by estrogen

3. Prolactin LevelProlactin Level
Underlying conditionUnderlying condition PRL levelPRL level
Prolactinoma.
Over 150 µg/L (five times
higher than normal values)
Psychoactive drugs, estrogen,
functional (idiopathic) or
microadenomas
Values between normal and
100 µg/L
Macroadenomas
Over 250 µg/L
In some cases over 1000 µg/L
Normal PRL level
Women: below 25 µg/L - Men: below 20 µg/L

4. Hyperprolactinaemia ManifestationsHyperprolactinaemia Manifestations
In Women:
•Disruptions of normal menstrual period (oligomenorrhea
/ amenorrhea)
•Hypogonadism, anovulation & Infertility
In Men:
•Signs of androgen deficiency and infertility (impotence, loss
of libido, and rarely gynecomastia and galactorrhea)
In both Sexes:
•Galactorrhea
•Tumor mass may cause visual-field defects or headache

5. Osteoporosis increased with elevated PRL due to estrogen lackOsteoporosis increased with elevated PRL due to estrogen lack
If normal menses are present, osteoporosis does not occurIf normal menses are present, osteoporosis does not occur
HyperprolactinemiaHyperprolactinemia
How frequent is it?How frequent is it?
Clinical symptoms Indicates elevated PRL in
Galactorrhea
10% of women
99% of men
Amenorrhea 15%
Galactorrhea plus amenorrhea 75%
Infertility 33%
PCO 19-50 %

7. Hyperprolactinemia Mechanisms onHyperprolactinemia Mechanisms on
Reproductive DysfunctionReproductive Dysfunction
A.A. Inhibition of pulsatile GnRH secretion
B.B. Interference with gonadotropin action in ovary
C.C. Interference with estrogen positive feedback
D.D. Inhibition of progesterone synthesis
E.E. Impaired follicle development
F.F. Inhibition of 5-alpha-reductase enzyme in men, thereby
decreasing the conversion of testosterone to DHT

8. Hyperprolactinemia InhibitsHyperprolactinemia Inhibits
progesterone synthesis and Impairsprogesterone synthesis and Impairs
follicle developmentfollicle development
• Prolactin is involved in the induction of LH
receptors to maintain progesterone synthesis.
• Prolactin is necessary for complete lutenization.
• Very high prolactin level in the early phase of follicular
growth inhibit progesterone secretion.
(J Endocrinol 64:555, 1975)
• If prolactin exceeds 100 ng/mL, 100% of the follicles
are atretic.
(Nature 250:653 1974)

9. CabergamounCabergamoun
cabergoline 0.5 mg tabcabergoline 0.5 mg tab
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10. Composition
Form
Pharmacological action
Preserved in
Pack
PRODUCT PROFILE
: 0.5mg cabergoline
: Scored tablets
: Prolactin Inhibitor
: PVC/PVDC strips
: One strip of 2 tablets
CabergamounCabergamoun

11. IS AN ERGOLINE DOPAMINE AGONIST WITH
Agonist activity on
D2 receptors
in pituitary lactotrophs
------- Potent -------
----- Selective -----
--- Long-lasting ---
As compared to bromocriptine
Cabergamoun is more potent in agonizing the D2 receptor and it
occupied the receptor for longer
CabergamounCabergamoun
Prolactin is down regulated by dopamine ..

12. • Cabergamoun has a potent and long-lasting
PRL-lowering effect by direct stimulation of D2-
receptors on lactotrophs
• Cabergamoun at higher doses, has a central dopaminergic effect
• Cabergamoun single oral administration of 0.25 - 1.5 mg,
produces a significant decrease in serum PRL levels.
CabergamounCabergamoun
PharmacodynamicsPharmacodynamics

13. • Cabergamoun has a prompt effect (within 3 hrs.
from administration) and persists for
- Up to 7 - 28 days in hyperprolactinemic patients
- up to 14 - 21 days in puerperal women
• Cabergamoun PRL-lowering effect is dose-related in terms of
degree of effect and duration of action
• Cabergamoun has a very selective action with no effect on
basal secretion of other pituitary hormones or cortisol
CabergamounCabergamoun
PharmacodynamicsPharmacodynamics

14. CabergamounCabergamoun
PharmacokineticsPharmacokinetics
• Cabergamoun absorption and disposition is not
affected by food.
• Cabergamoun is rapidly absorbed from the GIT
with a peak in plasma between 0.5 and 4 hours
• Cabergamoun is 41-42% bound to plasma proteins.

15. CabergamounCabergamoun
PharmacokineticsPharmacokinetics
• Cabergamoun elimination half-life is long
- 63-68 hours in healthy volunteers
- 79-115 hours in hyperprolactinemic patients
• Ten days after administration about 18% and 72% of the dose
is recovered in urine and feces, respectively
• Unchanged drug in urine accounted for 2-3% of the dose

16. CabergamounCabergamoun
Therapeutic IndicationsTherapeutic Indications
1. Inhibition of physiological lactation
2. Suppression of already established lactation
3. Treatment of dysfunctions associated wit hyperprolactinaemia:
“Amenorrhoea, oligomenorrhoea, anovulation, galactorrhea
and infertility”
4. Prolactin-secreting pituitary adenomas (micro- & macroadenoma)
5. Idiopathic hyperprolactinaemia
6. Empty sella syndrome* with associated hyperprolactinaemia
7. Prevention of ovarian hyper-stimulation syndrome

17. CabergamounCabergamoun
Dosage & AdministrationDosage & Administration

18. Indication Dose
Inhibition of lactation
1mg (two tablets) given as a single
dose on the first day after delivery
Suppression of
established lactation
0.25 mg (half a tablet) every 12 hours for 2
days (1 mg total dose)
Amenorrhea, infertility &
galactorrhea
Initial dose is 0.5 mg per week
Therapeutic dosage is usually 1 mg per week
Prevention of OHSS
One tablet daily for 8 days
starting on the day of HCG injection
CabergamounCabergamoun
Dosage & AdministrationDosage & Administration
Cabergamoun doses up to 4.5 mg per week
have been used in hyperprolactinemic patients

19. CabergamounCabergamoun
Normalizes PRL level in patients with
bromocriptine resistance or intolerance
JCE&M 84(7): 2518-2522; 1999.

20. CabergamounCabergamoun
Restores gonadal function in women with
hyperprolactinemic amenorrhea
New Engl J Med. 331(14):
904-909; 1994.
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21. CabergamounCabergamoun
Is well tolerated by all patients
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New Engl J Med. 331(14):
904-909; 1994.

22. CabergamounCabergamoun
Has better patient tolerability and
compliance than bromocriptine
Wang et al. Syatematic
Reviews 2012, 1:33
“Treatment of
hyperprolactinemia: a
systematic review and
meta-analysis”
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23. PITUITARYPITUITARY
ADENOMAADENOMA

26. Management of Pituitary AdenomaManagement of Pituitary Adenoma
Surgery
If cabergoline is not successful, trans-
sphenoidal surgery could be considered
Radiation
Observation
Pharmacotherapy
“Dopamine agonists are treatment of choice for most prolactinomas”
Cabergoline is more effective than bromocriptine
Liu, C, Tyrrell, JB. Successful treatment of a large
macroprolactinoma with cabergoline during pregnancy.
Pituitary 2001; 4:179.

27. Pharmacotherapy of ProlactinomaPharmacotherapy of Prolactinoma
• First evidence of size reduction may occur
after 6 weeks
• Size reduction does not correlate with basal PRL
or percentage reduction in PRL levels
• In first 2-3 years, most will re-expand
• After a few years, few re-expand

28. OVARIANOVARIAN
HYPERSTIMULATIONHYPERSTIMULATION
SYNDROMESYNDROME
““OHSS”OHSS”

30. Cabergamoun
•Reduces the risk of OHSS in high-risk women
•Dose: 0.5 mg (one tablet) daily0.5 mg (one tablet) daily
•Duration: starting on the day of HCG injectionDuration: starting on the day of HCG injection andand
continue for 8 dayscontinue for 8 days
Cabergamoun in OHSSCabergamoun in OHSS

31. POLYCYSTICPOLYCYSTIC
OVARIAN SYNDROMOVARIAN SYNDROM
“PCO”“PCO”

32. Ovulatory dysfunction - PCOOvulatory dysfunction - PCO
• 20% of all women on scan
• Overweight, hirsute, oligomenorrhoea & acne
• LH/FSH raised
• Raised androgens
• Mildly raised prolactin (in 19-50% of women with PCO -
may be due to the high estrogen levels present in PCO)

33. Cabergamoun in PCOCabergamoun in PCO
Cabergamoun
in hyperprolactinemia patients with PCO will:
– Reduces testosterone and LH levels
– Resumes ovulatory cycles.

34. Thank YouThank You