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Raised Blood Prolactin Levels (Hyperprolactinemia) in Women Undergoing Infertility Treatment

by Dr. Geoffrey Sher on November 23, 2016

Prolactin is a protein hormone (closely related to human growth hormone) that is secreted by specialized cells in the anterior part of the pituitary gland. In addition, the hormone is also produced and secreted by a broad range of other cells in the body, most prominently various immune cells, the brain and the lining of the uterus. Most cells respond to prolactin. In fact, it is hard to identify any tissue that does not have prolactin receptors.

Although prolactin’s major target organ is the breast where it stimulates development and milk production, the hormone has many other functions. Several hundred different actions have been reported for prolactin and

Immune cells are rich in prolactin receptors and certain types of lymphocytes in fact synthesize and secrete prolactin. These observations suggest that prolactin may to some extent act as a regulator of the body’s immune activity.

In an area in the brain known as the hypothalamus, a chemical called dopamine is released. Dopamine suppresses prolactin synthesis and release by the pituitary gland. As such it acts as a “hypothalamic brake set” causing prolactin only to be secreted when the “brake” is released. Treatment with dopamine agonists such as bromocriptine (Parlodel) and cabergoline (Dostinex) , by enhancing serotonin production lowers prolactin

Several other hypothalamic hormones, including thyroid releasing hormone (TRH) and gonadotropin releasing hormone (GnRH) cause an increase in prolactin secretion Stimulation of the nipples (including but not limited to nursing) leads to hypothalamic activation and prolactin release Estrogens also exerts a positive control over prolactin synthesis and secretion

Even modestly raised prolactin levels (20ng/ml-40ng/ml) can interfere with estrogen-induced endometrial proliferation as well as egg/ ovarian follicle growth and development. Accordingly treatment with dopamine agonists (bromocriptine/ Cabergoline) might be of benefit in such cases.

Increased PRL secretion reduces the pulsatility of GnRH impairing the pituitary production of FSH and LH and may directly impair the endocrine activity of ovarian follicles as well as endometrial response to estrogen. This can lead to dysfunctional or failed ovulation, a defective luteal phase, and a poorly developed endometrial response to estrogen (a thin endometrial lining). About n 5% of unselected, asymptomatic infertile women have hyperprolactinemia. In such cases long-term use of dopaminergic drugs such as bromocryptine and can normalized prolactin levels leading to reestablishment of functional ovulation and improved endometrial development. About half of the pregnancies occurring during dopaminergic therapy start after the first 6 months of this drug therapy. Treatment should continue for at least 1 year.

Common manifestations of significantly increased prolactin secretion (hyperprolactinemia):

  • In women:
    • Oligo/amenorrhea (reduction or absence of menstrual flow) and galactorrhea (excessive or spontaneous breast secretion of milk).
    • A modest elevation in blood prolactin can also point to an underlying state of hypothyroidism
    • Markedly elevated prolactin levels (i.e. >60ng/ml) might point to a prolactin producing pituitary macroadenoma or microadenoma as well as other intracranial lesions such as craniopharyngiomas, meningiomas etc.
  • In men: Such men rarely have galactorrhea
    • Hypogonadism,
    • Breast enlargement (gynecomastia)
    • Erectile dysfunction
    • Decreased Libido
    • Sperm dysfunction resulting in infertility and with impotence.

Causes of hyperprolactinemia: Main causes of pathologic hyperprolactinemia (40).

  • Idiopathic (commonest variety) ….cause unknown Acromegaly
  • Empty Sella Turcica
  • Renal Failure
  • Polycystic Ovarian Syndrome (PCOS)
  • Certain drugs:
    • Antipsychotic drugs ( phenothiazines, haloperidol, monoamine oxidases (MAO) risperidone, fluoxetine, butyrophenones,
    • Anti-emetics: metoclopramide, domperidone,
    • Tricyclic antidepressants
    • Opiates
    • Verapamil
    • Antihypertensives and Ganglion blockers

Drug-induced hyperprolactinemia can be reversed by modifying or withdrawing the causative medication. In cases where this cannot safely be done, bromocryptine derivatives can be used.

  • Pituitary adenomas (prolactinomas)
    •  Some pituitary adenomas are treated by surgical removal but in most case prolonged treatment with bromocryptine or cabergoline will effectively lower blood concentrations and lead to shrinkage/disappearance of the tumor. Such treatment is also safe during pregnancy.
    •  Intracranial lesions such as craniopharyngiomas, meningioma causing hyperprolactinemia are usually treated by surgical removal.

Hyperprolactinemia and Reproductive Dysfunction:

  • Hypothyroidism in women is often caused by an autoimmune process where antithyroid antibodies progressively replace thyroid glandular tissue with functionless connective tissue. In roughly 50% of such cases there will be increased uterine natural killer cell activity (NKa) which may profoundly impair implantation leading to “perceived infertility” or recurrent pregnancy loss. Thus, ATA with NKa can be present prior to the development of clinically overt autoimmune hypothyroidism (Hashimoto’s disease). Since women with NKa are often infertile, or experience recurrent pregnancy loss, it is important that any unexplained hyperprolactinemia associated with reproductive failure or infertility be evaluated for an immunologic implantation dysfunction (IID) through testing  for the presence of antithyroid antibodies and if the ATA level is elevated, that an NKa test (K-562 target cell test) be done. What is not often commonly recognized is that even in cases where autoimmune hypothyroidism is clinically overt, treatment with thyroid hormone replacement will usually not solve the reproductive dysfunction which will usually require selective immunotherapy with Intralipid (IL) infusions plus steroid therapy. IL is administered intravenously about 4-7 days prior to ovulation or egg retrieval and then repeated one more time upon biochemical confirmation of early pregnancy. The steroids are continued to the 8th  week of pregnancy and then tailed off over 2 weeks.
  • Ovarian Hyperstimulation Syndrome (OHS): Prolactin facilitates production by ovarian follicle cells of VEGF (a vasoactive substance that increases vascular permeability of blood vessels) In cases of severe ovarian With severe ovarian hyperstimulation syndrome (OHSS) where there are a large number of follicles present (>25) and the blood estradiol level is markedly elevated (4,000pg/ml), even modestly elevated prolactin release can markedly worsen the situation. There is strong evidence to suggest that women with ovarian Hyperstimulation (>20 follicles and blood estradiol levels that peak above 3,000pg/ml) who receive O.5mg of oral administration Cabergoline daily for 7 days, starting on the day of the hCG trigger, experience a significant reduction in the risk and severity of severe ovarian stimulation syndrome (OHSS). This is thought to be due to Cabergoline suppressing the production of vascular vasoactive substances such as VEGF that are produced by luteinized follicular granulosa cells, that increase the vascular permeability of local pelvic blood vessels.

 

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  • Kristin - May 2, 2018 reply

    Hello again! After my failed FET with daily oral Estrace and borderline thin-lining (8.03), I opted for a mock transfer/biopsy cycle with 0.2 (20mg/ml) delestrogen every three days and my lining successfully reached 9.8. On day 6 of PIO, following the biopsy (fasting/under anesthesia) my E2, Progesterone and Prolactin levels were measured and E2 was 600, Progesterone was 31 and Prolactin was 83. Previously during an unmedicated cycle my prolactin measured 14 so, I am waiting to retest the prolactin during my next (unmedicated) menstral cycle. I am concerned that even if my prolactin tests normal, the elevated prolactin while on FET estrogen/meds will prevent implantation and scared to move forward with our only euploid embryo under such circumstances. Is this a valid concern? What do you suggest?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 3, 2018 reply

    I would first get the prolactin to 60ng/ml) might point to a prolactin producing pituitary macroadenoma or microadenoma as well as other intracranial lesions such as craniopharyngiomas, meningiomas etc.
    • In men: Such men rarely have galactorrhea
    o Hypogonadism,
    o Breast enlargement (gynecomastia),
    o Erectile dysfunction
    o Decreased Libido,
    o Sperm dysfunction resulting in infertility and with impotence..

    Causes of hyperprolactinemia: Main causes of pathologic hyperprolactinemia (40).

    • Idiopathic (commonest variety) ….cause unknown Acromegaly
    • Empty Sella Turcica
    • Renal Failure
    • Polycystic Ovarian Syndrome (PCOS)
    • Certain drugs:
    o Antipsychotic drugs ( phenothiazines, haloperidol, monoamine oxidases (MAO) risperidone, fluoxetine, butyrophenones,
    o Anti-emetics: metoclopramide, domperidone,
    o Tricyclic antidepressants
    o Opiates
    o Verapamil
    o Antihypertensives and Ganglion blockers

    Drug-induced hyperprolactinemia can be reversed by modifying or withdrawing the causative medication. In cases where this cannot safely be done, bromocryptine derivatives can be used.

    • Pituitary adenomas (prolactinomas)
    o Some pituitary adenomas are treated by surgical removal but in most case prolonged treatment with bromocryptine or cabergoline will effectively lower blood concentrations and lead to shrinkage/disappearance of the tumor. Such treatment is also safe during pregnancy.
    o Intracranial lesions such as craniopharyngiomas, meningioma causing hyperprolactinemia are usually treated by surgical removal.

    Hyperprolactinemia and Reproductive Dysfunction:
    • Hypothyroidism in women is often caused by an autoimmune process where antithyroid antibodies progressively replace thyroid glandular tissue with functionless connective tissue. In roughly 50% of such cases there will be increased uterine natural killer cell activity (NKa) which may profoundly impair implantation leading to “perceived infertility” or recurrent pregnancy loss. Thus, ATA with NKa can be present prior to the development of clinically overt autoimmune hypothyroidism (Hashimoto’s disease). Since women with NKa are often infertile, or experience recurrent pregnancy loss, it is important that any unexplained hyperprolactinemia associated with reproductive failure or infertility be evaluated for an immunologic implantation dysfunction (IID) through testing for the presence of antithyroid antibodies and if the ATA level is elevated, that an NKa test (K-562 target cell test) be done. What is not often commonly recognized is that even in cases where autoimmune hypothyroidism is clinically overt, treatment with thyroid hormone replacement will usually not solve the reproductive dysfunction which will usually require selective immunotherapy with Intralipid (IL) infusions plus steroid therapy. IL is administered intravenously about 4-7 days prior to ovulation or egg retrieval and then repeated one more time upon biochemical confirmation of early pregnancy. The steroids are continued to the 8th week of pregnancy and then tailed off over 2 weeks.

    • Ovarian Hyperstimulation Syndrome (OHS): Prolactin facilitates production by ovarian follicle cells of VEGF (a vasoactive substance that increases vascular permeability of blood vessels) In cases of severe ovarian With severe ovarian hyperstimulation syndrome (OHSS) where there are a large number of follicles present (>25) and the blood estradiol level is markedly elevated (4,000pg/ml), even modestly elevated prolactin release can markedly worsen the situation. There is strong evidence to suggest that women with ovarian Hyperstimulation (>20 follicles and blood estradiol levels that peak above 3,000pg/ml) who receive O.5mg of oral administration Cabergoline daily for 7 days, starting on the day of the hCG trigger, experience a significant reduction in the risk and severity of severe ovarian stimulation syndrome (OHSS). This is thought to be due to Cabergoline suppressing the production of vascular vasoactive substances such as VEGF that are produced by luteinized follicular granulosa cells, that increase the vascular permeability of local pelvic blood vessels.
    Geoff Sher

    Kristin - May 3, 2018 reply

    Thank you for your reply. Certainly sounds like an uphill battle to address this newly discovered concern. At 42 I don’t have the luxury of time to waSte and I’m feeling totally overwhelmed and defeated already. I had a brain MRI a couple years ago (relative to migraine headaches) and nothing was identified then but, it sounds as if a repeat is in order. If an MRI yields nothing new, I am on 100mg Lamictal daily (for years) and wonder if this could be the culprit… if that was suspected, I would want to safely stop taking it before proceeding to FET.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 3, 2018 reply

    Lamictal CAN increase blood prolactin levels.

    Geoff Sher

  • Lia - April 15, 2018 reply

    Hi dr. Sher,
    I’m a 31 years old woman and unfortunatly I need to take psychotropic drugs which include low dose amisulpride (50 mg a day). As a consequence I have very elevated prolactin levels. In future I would like to try ivf with egg donation. Is there a chance to be succesfull without shopping my meds nor taking dopamin agonists? Could antagonists of prolactin receptor be used insead of dopamina agonists?
    Thanks

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 16, 2018 reply

    Yes indeed! It should in my opinion not pose a major problem.

    Geoff Sher

  • Danielle - April 6, 2018 reply

    Does prolactinoma affect egg quality? What protocol is recommended for women with prolactinoma? I think my protocol might be what is giving me horrible results (50eggs from two cycles and only 6 blastocysts and a failed transfer). 150iu menopur, 150iu gonal, cetrotide, Ovidrel has been my protocol. Most embryos are c quality with only a few a or b and after day 2 or 3 they stop developing. Will hgh help me? Should we test for auto immune, killer cells, era, mthfr?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 7, 2018 reply

    Hi Danielle.

    Once the prolactin level is restored to normal, the prolactinoma shouldx have no effect on the protocol. However there seems to be another issue and that is that you are a very high responder and at risk of developing severe ovarian hypersimulation. Patients such as you, require that a great deal of planning an individualized protocol for ovarian stimulation be designed and implemented. If Ovidrel is used it must in my opinion be 500mcg for the trigger, rather than 250mcg.

    Typically, women with irregular ovulation/menstruation, young women, those with high ovarian reserve (AMH=>6ng/ml) and those who have polycystic ovarian syndrome (PCOS) who undergo ovarian stimulation with fertility drugs are at increased risk of developing severe ovarian hyperstimulation syndrome (OHSS), a life endangering condition. In cases of OHSS egg “competency” (quality) is often severely compromised.
    The fear of OHSS developing often prompts RE’s to trigger egg maturation prematurely with hCG in the hope of arresting the process before ovarian stimulation spirals out of control, increasing physical risk and causing a high percentage of harvested eggs to end up being “incompetent”, (“immature/dysmature).
    Also in an attempt to reduce the risks of OHSS, some RE’s trigger egg maturation using a reduced dosage of hCG or through inducing an outpouring of pituitary LH an agonist such as Lupron or Buserelin. While such approaches indeed reduce the risk and severity of OHSS, they often result in many eggs failing to mature. Thus lowering risk by reducing the dosage of hCG or by using an agonist “trigger”, often comes at the expense of egg “competency”.
    In women with PCOS, poor egg “competency” is also often attributable to high ovarian LH-induced testosterone. Such eggs have reduced fertilization potential, often yielding “poor quality embryos”. While poor egg “competency” in women with PCOS can be due to the fact that such eggs are more prone to having intrinsic quality deficits, it is (in my opinion), more commonly attributable to aberrant intra-ovarian hormonal changes brought about by severe ovarian hyperstimulation. This effect, can be prevented or curtailed through implementation of individualized or customized ovarian stimulation protocols that minimize over-exposure to excessive LH-induced ovarian male hormones (androgens) which can best be accomplished by limiting the use of LH-containing gonadotropins such as Menopur and by using a procedure that I introduced in 1989, known as “prolonged coasting” (see below).
    Approaches to preventing or containing OHSS include:
    1. PROLONGED COASTING: My preferred approach is to use a long pituitary DR protocol coming off up to 2 months on the BCP, overlapped in the last 3 days with the agonist, Lupron. The BCP is intended to lower LH and thereby reduce stromal activation (hyperthecosis) in the hope of controlling ovarian androgen (predominantly, testosterone) production and release. I then stimulate with low dosage recombinant FSF-FSHr (Follistim/Gonal-F/Puregon) to which I add a smidgeon of LH/hCG (Luveris/Menopur) from the 3rd day. Then, starting on day 7 of ovarian stimulation, I perform serial blood estradiol (E2) and ultrasound follicle assessments, watching for the # of follicles and [E2]. If there are > 25 follicles, I keep stimulating (regardless of the [E2] until 50% of all follicles reach 14mm. At this point, provided the [E2] reaches at least >2,500pg/ml, I stop the agonist as well as gonadotropin stimulation and track the blood E2 (without continuing US, follicle measurements) ) daily. The [E2] will almost invariably increase for a few days. I watch the E2 rise (regardless of how high a blood concentration it reaches) and then track it coming down again. As soon as the [E2] drops below 2500pg/ml (and not before then), I administer a “trigger” shot of 10,000U hCGu (Profasi/ Novarel/Pregnyl) or hCGr (Ovidrel/Ovitrel-500mcg) and perform an egg retrieval 36 hours later. ICSI is a MUST because “coasted” eggs usually have no cumulus oophoris envelopment and eggs without a cumulus will not readily fertilize naturally. Moreover, they also tend to have a “hardened” envelopment (zona pellucida), making spontaneous fertilization problematic in many cases. All fertilized eggs are cultured to blastocyst (up to 6 days) and are then either vitrified and preserved for subsequent transfer in later hormone replacement cycles or up to two (2) fresh blastocysts are transferred transvaginal under US guidance.. The success of this approach depends on precise timing of the initiation and conclusion of “prolonged coasting”. If you start too early, follicle growth will stop and the cycle will be lost. If you start too late, you will encounter too many post-mature/cystic follicles (>22mm) that usually harbor abnormally developed eggs. Use of “Coasting” avoids unnecessary cycle cancellation, severe OHSS, and optimizes egg/embryo quality. The worst you will encounter is mild to moderate OHSS and this too is uncommon. The obvious remedy for these adverse effects on egg and endometrial development is to employ stimulation protocols that limit ovarian over-exposure to LH and allowing the time necessary for the follicles/eggs to develop optimally, prior to administering hCG through the judicious implementation of “Prolonged coasting” (PC).

    2.TRIGGERING WITH LOW DOISAGE hCG; Because of the fact that hCG augments the development of OHSS (unless preceded by “coasting”), may RE’s prefer to use a lower dosage of hCG for the “trigger. This is either done by administering 5,000U (half the traditional dosage) or by administering, a 250mcg (rather than 500mcg) of DNA recombinant form of hCGr (Ovidrel/Ovitrel. Some clinicians, when faced with a risk of OHSS developing will deliberately elect to reduce the “trigger” dosage of hCG administered (from 10,000U to 5,000U or 250mcg of recombinant hCG-Ovidrel) in the hope that by doing so the risk of critical OHSS developing will be lowered. While this might indeed be true, it is my opinion, that such a reduced dosage is usually insufficient to optimize the efficiency of egg meiosis, e3specially when there are so many follicles present. While the use of a reduced “trigger” dosage of hCG does indeed reduce the risk and occurrence of OHSS-related life-endangering complications, the price to be paid is reduced egg quality/”competency”.
    3. “TRIGGERING” WITH A GnRH AGONIST (E.G. “LUPRON/BUSERELIN): More recently, an increasing number of RE’s prefer to trigger meiosis by way of an agonist (Lupron/Buserelin/Superfact () “trigger” rather than through the use of hCG. The idea is to mimic what happens in natural cycles to promote egg maturation (meiosis) and ovulation, namely to have the agonist cause a “surge” in the release of body’s own pituitary LH to trigger egg meiosis (maturation) .But the amount of LH released in by the pituitary gland is often insufficient to optimize meiotic egg maturation and thus, while this approach also lowers the risk of OHSS it again comes at the expense of egg quality/competency.

    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • The Fundamental Requirements For Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting.
    • “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
    • The “Lupron Trigger” to Prevent Severe OHSS: What are the Pro’s and Con’s?
    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *The 4th edition of my book,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

    d

  • Tracey - October 20, 2017 reply

    I had a raised prolactin level of 2010 and was found to have a prolactinoma 20 years ago and have been taken medication ever since. I now have hyperprolactimemia. I haven’t taken my meds for 8 weeks due to vomiting and my levels have just come back at 533. Is there anything else I can try if I can’t take my tablets anymore? I am currently taking norprolec/quinagolide. I have had sever health problems since developing vitiligo 2 years ago but don’t think they are connected.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - October 20, 2017 reply

    They are highly unlikely to be connected. I cannot comment on your present prolactin levels. This is definitely something you need to discuss with your treating endocrinologist. It is likely you will need a follow-up MRI of the pituitary gland also!

    Geoff Sher

  • Katie - September 22, 2017 reply

    Dr Sher-
    I have recently discovered I have slightly elevated prolactin levels (30) and galactorrhea. My current doctor does not want to treat it because I also have slightly elevated FSH ( 12.) He says treating the prolactin will cause FSH to increase, as elevated prolactin suppresses FSH production. We’ve been trying to conceive for about a year ( I’m 36) and we do have one son conceived naturally 3 years ago. I’m frustrated- everything I read says I should treat the prolactin level, but now he’s got me scared that my FSH will skyrocket and I’ll be in even worse shape. What are your thoughts?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 22, 2017 reply

    Prolactin is a protein hormone (closely related to human growth hormone) that is secreted by specialized cells in the anterior part of the pituitary gland. In addition, the hormone is also produced and secreted by a broad range of other cells in the body, most prominently various immune cells, the brain and the lining of the uterus. Most cells respond to prolactin. In fact it is hard to identify any tissue that does not have prolactin receptors.
    Although prolactin’s major target organ is the breast where it stimulates development and milk production, the hormone has many other functions. Several hundred different actions have been reported for prolactin and
    Immune cells are rich in prolactin receptors and certain types of lymphocytes in fact synthesize and secrete prolactin. These observations suggest that prolactin may to some extent act as a regulator of the body’s immune activity.
    In an area in the brain known as the hypothalamus, a chemical called dopamine is released. Dopamine suppresses prolactin synthesis and release by the pituitary gland. As such it acts as a “hypothalamic brake set” causing prolactin only to be secreted when the “brake” is released. Treatment with dopamine agonists such as bromocriptine (Parlodel) and cabergoline (Dostinex) , by enhancing serotonin production lowers prolactin
    Several other hypothalamic hormones, including thyroid releasing hormone (TRH) and gonadotropin releasing hormone (GnRH) cause an increase in prolactin secretion Stimulation of the nipples (including but not limited to nursing) leads to hypothalamic activation and prolactin release Estrogens also exerts a positive control over prolactin synthesis and secretion
    Even modestly raised prolactin levels (20ng/ml-40ng/ml) can interfere with estrogen-induced endometrial proliferation as well as egg/ ovarian follicle growth and development. Accordingly treatment with dopamine agonists (bromocriptine/ Cabergoline) might be of benefit in such cases.
    Increased PRL secretion reduces the pulsatility of GnRH impairing the pituitary production of FSH and LH and may directly impair the endocrine activity of ovarian follicles as well as endometrial response to estrogen. This can lead to dysfunctional or failed ovulation, a defective luteal phase, and a poorly developed endometrial response to estrogen (a thin endometrial lining). About n 5% of unselected, asymptomatic infertile women have hyperprolactinemia. In such cases long-term use of dopaminergic drugs such as bromocryptine and can normalized prolactin levels leading to reestablishment of functional ovulation and improved endometrial development. About half of the pregnancies occurring during dopaminergic therapy start after the first 6 months of this drug therapy. Treatment should continue for at least 1 year.

    Common manifestations of significantly increased prolactin secretion (hyperprolactinemia):
    • In women:
    o Oligo/amenorrhea (reduction or absence of menstrual flow) and galactorrhea (excessive or spontaneous breast secretion of milk).
    o A modest elevation in blood prolactin can also point to an underlying state of hypothyroidism
    o Markedly elevated prolactin levels (i.e. >60ng/ml) might point to a prolactin producing pituitary macroadenoma or microadenoma as well as other intracranial lesions such as craniopharyngiomas, meningiomas etc.
    • In men: Such men rarely have galactorrhea
    o Hypogonadism,
    o Breast enlargement (gynecomastia),
    o Erectile dysfunction
    o Decreased Libido,
    o Sperm dysfunction resulting in infertility and with impotence..

    Causes of hyperprolactinemia:
    • Certain drugs: (e.g. tranquilizers, ganglion blocker antihypertensives, antidepressants, thiazides and narcotics) can also lead to significant elevations in prolactin. Drug-induced hyperprolactinemia can be reversed by modifying or withdrawing the causative medication. In cases where this cannot safely be done, bromocryptine derivatives can be used.
    • Pituitary adenomas (prolactinomas)
    o Some pituitary adenomas are treated by surgical removal but in most case prolonged treatment with bromocryptine or cabergoline will effectively lower blood concentrations and lead to shrinkage/disappearance of the tumor. Such treatment is also safe during pregnancy.
    o Intracranial lesions such as craniopharyngiomas, meningioma causing hyperprolactinemia are usually treated by surgical removal.
    Hyperprolactinemia and Reproductive Dysfunction:
    • Hypothyroidism in women is often caused by an autoimmune process where antithyroid antibodies progressively replace thyroid glandular tissue with functionless connective tissue. In roughly 50% of such cases there will be increased uterine natural killer cell activity (NKa) which may profoundly impair implantation leading to “perceived infertility” or recurrent pregnancy loss. Thus, ATA with NKa can be present prior to the development of clinically overt autoimmune hypothyroidism (Hashimoto’s disease). Since women with NKa are often infertile, or experience recurrent pregnancy loss, it is important that any unexplained hyperprolactinemia associated with reproductive failure or infertility be evaluated for an immunologic implantation dysfunction (IID) through testing for the presence of antithyroid antibodies and if the ATA level is elevated, that an NKa test (K-562 target cell test) be done. What is not often commonly recognized is that even in cases where autoimmune hypothyroidism is clinically overt, treatment with thyroid hormone replacement will usually not solve the reproductive dysfunction which will usually require selective immunotherapy with Intralipid (IL) infusions plus steroid therapy. IL is administered intravenously about 4-7 days prior to ovulation or egg retrieval and then repeated one more time upon biochemical confirmation of early pregnancy. The steroids are continued to the 8th week of pregnancy and then tailed off over 2 weeks.

    • Ovarian Hyperstimulation Syndrome (OHS): Prolactin facilitates production by ovarian follicle cells of VEGF (a vasoactive substance that increases vascular permeability of blood vessels) In cases of severe ovarian With severe ovarian hyperstimulation syndrome (OHSS) where there are a large number of follicles present (>25) and the blood estradiol level is markedly elevated (4,000pg/ml), even modestly elevated prolactin release can markedly worsen the situation. There is strong evidence to suggest that women with ovarian Hyperstimulation (>20 follicles and blood estradiol levels that peak above 3,000pg/ml) who receive O.5mg of oral administration Cabergoline daily for 7 days, starting on the day of the hCG trigger, experience a significant reduction in the risk and severity of severe ovarian stimulation syndrome (OHSS). This is thought to be due to Cabergoline suppressing the production of vascular vasoactive substances such as VEGF that are produced by luteinized follicular granulosa cells, that increase the vascular permeability of local pelvic blood vessels.

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .
    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

  • Celia - June 16, 2017 reply

    Dr. Sher,
    Can elevated prolactin affect the AMH and FSH level and AFC? Thanks!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - June 16, 2017 reply

    I doubt it!

    Geoff Sher

  • Celia - June 14, 2017 reply

    does it usually take long to bring the prolactin level down with meds? And the meds is save to take during ivf and pregnancy?

    Thanks again!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - June 14, 2017 reply

    It should come down within about 2 weeks and yes, in my opinion it is relatively safe.

    Prolactin is a protein hormone (closely related to human growth hormone) that is secreted by specialized cells in the anterior part of the pituitary gland. In addition, the hormone is also produced and secreted by a broad range of other cells in the body, most prominently various immune cells, the brain and the lining of the uterus. Most cells respond to prolactin. In fact it is hard to identify any tissue that does not have prolactin receptors.
    Although prolactin’s major target organ is the breast where it stimulates development and milk production, the hormone has many other functions. Several hundred different actions have been reported for prolactin and
    Immune cells are rich in prolactin receptors and certain types of lymphocytes in fact synthesize and secrete prolactin. These observations suggest that prolactin may to some extent act as a regulator of the body’s immune activity.
    In an area in the brain known as the hypothalamus, a chemical called dopamine is released. Dopamine suppresses prolactin synthesis and release by the pituitary gland. As such it acts as a “hypothalamic brake set” causing prolactin only to be secreted when the “brake” is released. Treatment with dopamine agonists such as bromocriptine (Parlodel) and cabergoline (Dostinex) , by enhancing serotonin production lowers prolactin
    Several other hypothalamic hormones, including thyroid releasing hormone (TRH) and gonadotropin releasing hormone (GnRH) cause an increase in prolactin secretion Stimulation of the nipples (including but not limited to nursing) leads to hypothalamic activation and prolactin release Estrogens also exerts a positive control over prolactin synthesis and secretion
    Even modestly raised prolactin levels (20ng/ml-40ng/ml) can interfere with estrogen-induced endometrial proliferation as well as egg/ ovarian follicle growth and development. Accordingly treatment with dopamine agonists (bromocriptine/ Cabergoline) might be of benefit in such cases.
    Increased PRL secretion reduces the pulsatility of GnRH impairing the pituitary production of FSH and LH and may directly impair the endocrine activity of ovarian follicles as well as endometrial response to estrogen. This can lead to dysfunctional or failed ovulation, a defective luteal phase, and a poorly developed endometrial response to estrogen (a thin endometrial lining). About n 5% of unselected, asymptomatic infertile women have hyperprolactinemia. In such cases long-term use of dopaminergic drugs such as bromocryptine and can normalized prolactin levels leading to reestablishment of functional ovulation and improved endometrial development. About half of the pregnancies occurring during dopaminergic therapy start after the first 6 months of this drug therapy. Treatment should continue for at least 1 year.

    Common manifestations of significantly increased prolactin secretion (hyperprolactinemia):
    • In women:
    o Oligo/amenorrhea (reduction or absence of menstrual flow) and galactorrhea (excessive or spontaneous breast secretion of milk).
    o A modest elevation in blood prolactin can also point to an underlying state of hypothyroidism
    o Markedly elevated prolactin levels (i.e. >60ng/ml) might point to a prolactin producing pituitary macroadenoma or microadenoma as well as other intracranial lesions such as craniopharyngiomas, meningiomas etc.
    • In men: Such men rarely have galactorrhea
    o Hypogonadism,
    o Breast enlargement (gynecomastia),
    o Erectile dysfunction
    o Decreased Libido,
    o Sperm dysfunction resulting in infertility and with impotence..

    Causes of hyperprolactinemia: Main causes of pathologic hyperprolactinemia (40).

    • Idiopathic (commonest variety) ….cause unknown Acromegaly
    • Empty Sella Turcica
    • Renal Failure
    • Polycystic Ovarian Syndrome (PCOS)
    • Certain drugs:
    o Antipsychotic drugs ( phenothiazines, haloperidol, monoamine oxidases (MAO) risperidone, fluoxetine, butyrophenones,
    o Anti-emetics: metoclopramide, domperidone,
    o Tricyclic antidepressants
    o Opiates
    o Verapamil
    o Antihypertensives and Ganglion blockers

    Drug-induced hyperprolactinemia can be reversed by modifying or withdrawing the causative medication. In cases where this cannot safely be done, bromocryptine derivatives can be used.

    • Pituitary adenomas (prolactinomas)
    o Some pituitary adenomas are treated by surgical removal but in most case prolonged treatment with bromocryptine or cabergoline will effectively lower blood concentrations and lead to shrinkage/disappearance of the tumor. Such treatment is also safe during pregnancy.
    o Intracranial lesions such as craniopharyngiomas, meningioma causing hyperprolactinemia are usually treated by surgical removal.

    Hyperprolactinemia and Reproductive Dysfunction:
    • Hypothyroidism in women is often caused by an autoimmune process where antithyroid antibodies progressively replace thyroid glandular tissue with functionless connective tissue. In roughly 50% of such cases there will be increased uterine natural killer cell activity (NKa) which may profoundly impair implantation leading to “perceived infertility” or recurrent pregnancy loss. Thus, ATA with NKa can be present prior to the development of clinically overt autoimmune hypothyroidism (Hashimoto’s disease). Since women with NKa are often infertile, or experience recurrent pregnancy loss, it is important that any unexplained hyperprolactinemia associated with reproductive failure or infertility be evaluated for an immunologic implantation dysfunction (IID) through testing for the presence of antithyroid antibodies and if the ATA level is elevated, that an NKa test (K-562 target cell test) be done. What is not often commonly recognized is that even in cases where autoimmune hypothyroidism is clinically overt, treatment with thyroid hormone replacement will usually not solve the reproductive dysfunction which will usually require selective immunotherapy with Intralipid (IL) infusions plus steroid therapy. IL is administered intravenously about 4-7 days prior to ovulation or egg retrieval and then repeated one more time upon biochemical confirmation of early pregnancy. The steroids are continued to the 8th week of pregnancy and then tailed off over 2 weeks.

    • Ovarian Hyperstimulation Syndrome (OHS): Prolactin facilitates production by ovarian follicle cells of VEGF (a vasoactive substance that increases vascular permeability of blood vessels) In cases of severe ovarian With severe ovarian hyperstimulation syndrome (OHSS) where there are a large number of follicles present (>25) and the blood estradiol level is markedly elevated (4,000pg/ml), even modestly elevated prolactin release can markedly worsen the situation. There is strong evidence to suggest that women with ovarian Hyperstimulation (>20 follicles and blood estradiol levels that peak above 3,000pg/ml) who receive O.5mg of oral administration Cabergoline daily for 7 days, starting on the day of the hCG trigger, experience a significant reduction in the risk and severity of severe ovarian stimulation syndrome (OHSS). This is thought to be due to Cabergoline suppressing the production of vascular vasoactive substances such as VEGF that are produced by luteinized follicular granulosa cells, that increase the vascular permeability of local pelvic blood vessels.

    Geoff Sher

  • Celia - June 14, 2017 reply

    Hi Dr. Sher,
    I have elevated prolactin level (42) and was diagnosed with a small prolactinoma in the pituitary gland. On top of that, I am 41 yrs old and have DOR. My period is regular and i don’ t have any visual problems yet. Can the elevated prolactin affect egg quality? Can I have eggs retrieved and banked before the prolactin level is lowered and have the transfer done after the level is normal.
    Thanks!!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - June 14, 2017 reply

    If I were you, I would first bring the prolactin down before doing ovarian stimulation.

    Geoff Sher

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