HYPERPROLACTINAEMIA

Hyperprolactinaemia results from excessive
stimulation of the prolactin secreting cells
in the pituitary gland and leads to a
shortening of the luteal phase resulting in
infertility and increased progesterone
levels.

Prolactin is a pituitary derived hormone that:
◦ plays a pivotal role
reproductive functions;
in
a
variety
of
◦ Is essential for normal production of breast
milk following childbirth;
◦ Modulates
the
secretion
of
pituitary
hormones responsible for gonadal function
including:
 Luteinizing hormone (LH)
 Follicle stimulating hormone (FSH)

There can be three types of causes:
◦ Physiological
 During pregnancy
 lactation
◦ Pharmacological
 use of neuroleptics
 oestrogen
◦ Pathological
 Primary hypothyroidism
 Renal or hepatic insufficiency
oProlactin is cleared less rapidly from the
systemic circulation, which results in
increased blood levels of prolactin
 Hypothalamic
or
pituitary
disease
interfering with the secretion of dopamine,
ie, prolactinomas :
◦ Prolactinomas - benign tumour (adenoma) of
the pituitary gland that produces a hormone
called prolactin. It is the most common type
of pituitary tumour
A prolactinoma will secrete prolactin.
 These tumours may interrupt dopamine
delivery from the hypothalamus to the
pituitary, resulting in loss of inhibition of
prolactin release.


Cushing’s Disease :
a hormonal disorder caused by high levels of
cortisol. Symptoms include upper body
obesity, rounded face, increased fat around the
neck, thinning arms and legs, fatigue,
weakness, high blood pressure, and mood
disorders. Children tend to be obese with
slowed growth rates.
Pituitary adenomas cause most cases of Cushing's
syndrome. They are benign, or non-cancerous,
tumours of the pituitary gland which secrete
increased amounts of ACTH, (adrenocorticotropin),
a hormone that stimulates the adrenal glands.
Cushing's syndrome can also be caused by taking
glucocorticoid hormones such as prednisone for
asthma, rheumatoid arthritis, lupus and other
inflammatory diseases, or for immunosuppression
after transplantation. It may also develop because
of overproduction of cortisol by the body, or
adrenal tumours.
◦ The effects of medications that inhibit
dopamine release, thus leading to reduced
inhibition
and
increased
prolactin
production:
 Clomid, used for infertility, could be a
factor
in
the
development
of
hyperprolactinaemia which can then cause
infertility. It has been implicated in the
possibility of miscarriage and ectopic
pregnancies as well as the development of
PCOS.
 Neuroleptics  phenothiazines, haloperidol
 (Anti-psychotic drugs)
 Antihypertensives

blockers, methyldopa
 Psychotropic
agents
antidepressants
calcium-channel

tricyclic
 Anti-ulcer agents  H antagonists
2
 Opiates
 Oral contraceptives
◦ Hypothyroidism
(Serri, O., Chik, CL., Ur, R., Ezzat, S. 2003, ‘Diagnosis and
treatment of hyperprolactinaemia’, Canadian Medical Association Journal, vol.169, no.6, pp.575-577)
 In response to the hypothyroid state, a
compensatory increase in the discharge
of central hypothalamic thyroidotropinreleasing hormone results in increased
stimulation of prolactin secretion.
 Furthermore, Prolactin elimination from
the systemic circulation is reduced,
which contributes to increased prolactin
concentrations
o
o
An autoimmune condition of the pituitary
with lymphocytic infiltration can lead to
hyperprolactinaemia and is typically noted
in the postpartum phase in women of
childbearing age. Spontaneous resolution
is common.
Suckling in the breast-feeding woman
stimulates prolactin release. As well,
breast stimulation in some non-breast
feeding women and rarely in some men
may also cause an increase in serum
prolactin levels.
◦ It can also be related to Polycystic Ovarian
Syndrome:
 About 25% of PCOS patients exhibit
elevated
prolactin,
known
as
hyperprolactinemia.
 Hyperprolactinemia
results
from
abnormal oestrogen negative feedback
via the pituitary gland.
 Elevated prolactin can in turn contribute
to elevated oestrogen levels.



An excess of prolactin can be found in up to
10% of the population
The prevalence is about 5% among men who
present with impotence and infertility
The rate is higher among people with specific
symptoms that may be attributable to
hyperprolactinaemia, that is, up to:
◦ 9% among women with amenorrhea
◦ 25% among women with galactorrhea
◦ 70% among women with both amenorrhea
and galactorrhea

PREMENOPAUSAL WOMEN
◦ Marked
prolactin
excess
(<100ug/L
[normally >25ug/L] is associated with
hypogonadism, galactorrhea and amenorrhea
◦ Moderate prolactin excess (51 – 75ug/L) is
associated with oligomenorrhea
◦ Mild prolactin excess (35 – 50ug/L) is
associated with short luteal phase, decreased
libido and infertility
◦ Increased body weight may be associated
with prolactin-secreting pituitary tumour
◦ Osteopenia is present mainly in people with
associated hypogonadism
◦ Degree of bone loss is related to duration and
severity of hypogonadism

MEN
◦ Hyperprolactinaemia
presents
with
decreased libido, impotence, decreased
sperm production, infertility, and, rarely,
galactorrhea
◦ Impotence is unresponsive to testosterone
treatment
and
is
associated
with
decreased muscle mass, body hair and
osteoporosis.
TREATMENT PROTOCOL

Provide a dopaminergic reaction that will
inhibit prolactin, therefore normalising the
luteal phase and increasing the possibility of
pregnancy and the prevention of miscarriage
◦ False Unicorn Root
 Dysfunction in the female reproductive
system,
threatened
miscarriage
and
infertility (Bone 2003)
 Kings American Dispensary (1898) listed it
to remove the tendency to repeated and
successive
miscarriages
and
for
atrophy of the reproductive organs.
◦ Glycyrrhiza glabra
 Glycyrrhizin has been shown to lower
testosterone (Armanini,D., Bonanni,G., Palermo,M., 1999, ‘Reduction of
serum testosterone in men by licorice’, New England Journal of Medicine, Oct
7;341(15);1158)
 Licorice and peony have been shown to
act directly on the pituitary gland to
counteract hyperprolactinaemia (Bone 2004). It
has been shown to stimulate the
dopamine receptors and stimulate the
ovarian production of oestrogen by
stimulating aromatase activity.
◦ Paeonia lactiflora
 Is part of the shakuyaku-kanzo-to
formula, with licorice, used to improve
fertility in women affected by PCOS
(Takahashi,K.,
Kitao,M., 1994, ‘Effect of TJ-68 (shakuyaka-kanzo-to) on polycystic ovarian disease’ International Journal
of Fertility and Menopausal Studies, 39:69-76)
 In another study, 90% of women taking a
Licorice and peony combination showed
decreased progesterone levels and 25%
became pregnant
(Takahashi,K., Yoshino,K., Shirai,T., Nishigaki,A., Araki,Y.,
Kitao,M., 1988, ‘Effect of a traditional herbal medicine (shakuyaka-kanzo-to) on testosterone secretion in
patients with polycystic ovary syndrome detected by ultrasound’, Nippon Sanka Jujinka Gakkai Zasshi,
Jun;40(6):789-92)
 Peony has been shown to reduce sexual
dysfunction in men, reportedly caused by
neuroleptic-induced hyperprolactinemia.
(Peony monograph, Alternative Medicine Review, Oct 2001 v6 i5 p495)
 Women with dysmenorrhea and/or
amenorrhea due to use of the
neuroleptic drug risperidone benefited
from shakuyaku-kanzo-to according to
another report
Alternative Medicine Review
(Peony monograph,
p495)
, Oct 2001 v6 i5
◦ Asparagus racemosus
 Shativari is well known for its effects on
the female reproductive system. For
balancing hormonal system of women,
Shativari may be used for regulating
menstruation and ovulation, improving
lactation, decreasing morning sickness,
infertility,
Menopause,
Leukorrhea,
inflammation of sexual organs, and
general sexual debility.
(http://www.shatavari.com/)
 The male reproductive system will also
benefit from Shativari as it may be used in
cases of sexual debility, impotence,
Spermatorrhea, and inflammation of
Sexual organs.
◦ Vitex agnus-castus
 Shown to have dopaminergic activity associated
with the inhibition of prolactin synthesis and
release in hyperprolactinaemia (Heinrich et al 2004)
 52 women with luteal phase defects due to
latent hyperprolactinaemia were given a
daily dose was one capsule (20 mg) Vitex
agnus castus preparation and placebo,
respectively. 37 complete case reports
(placebo: n = 20) after 3 month of therapy
were statistically evaluated. The prolactin
release was reduced after 3 months,
shortened luteal phases were normalised
and deficits in the luteal progesterone
synthesis were eliminated.
(Milewicz, A., Geidel, E., Sworen, H., Sienkiewicz,
K., Jedrzeiak, J., Teucher, T., Schmitz, H. 1993, ‘Vitex agnus castus extract in the treatment of luteal phase defects due to
latent hyperprolactinemia. Results of a randomized placebo-controlled double-blind study’, Arzneimittelforschung, vol.43,
no.7, pp.752-6)

Vitex is a popular treatment for mastalgia. Two
randomised, double blind studies confirm its
usefulness as a treatment in premenstrual
mastalgia. According to one study, symptom
relief was experienced after the first month of
treatment, with continued improvements after
the second and third months. In each study,
chaste tree reduced serum prolactin levels.
(Wuttke,W.,
Jerry,H., Christoffel,V., Spengler,B., Seldiova-Wuttke,D. 2003, ‘Chaste tree (Vitex agnus castus)- pharmacology and clinical
indicaqtions’, Phytomedicine, vol.10, pp.348-357)

Prolactin works like a stress barometer.
Evidence exists to prove that vitex can
clinically lower prolactin levels. Research from
both in vitro and in vivo studies have indicated
that vitex acts on the D2 receptors to decrease
prolactin levels.
(Braun, L. 2006, “Vitex agnus-castus: Chasteberry”, The Journal of Complementary
Medicine, vol.5, no.4, pp.71-71)

Deal with the stress, anxiety and other nervous
system issues that may be affecting the
prolactin levels
◦
◦
◦
◦
◦


Hypericum perforatum
Panax ginseng
Glycyrrhiza glabra
Schisandra sinensis
Withania somnifera
Prevention of osteoporosis
◦ Red Clover’s effect on preventing bone loss
after menopause.
Support the treatment of the pituitary tumour
if present

Liver support to deal with any dysfunction and to
enhance the metabolism of hormones
◦ Schisandra sinensis
 liver detoxification, hepatoprotective, antioxidant,
and anti-inflammatory (Heinrich et al 2004)
◦ Silybum marianum

Other considerations
◦ Research has shown that elevated levels of
homocysteine can be responsible for recurrent
miscarriages (Ronnenberg AG., Goldman MB., Chen D., Aitken IW., Willett WC., Selhub J & Xu X, 2002
‘Preconception homocysteine and vitamin B status and birth outcomes in Chinese women’ American Journal of Clinical
Nutrition, 76(6):1385-91)
◦ Beer increases prolactin levels and must be avoided
(Bone 2004)