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Prolactin, bone loss, prolactinomas, and common medications

February 17, 2010

I ran across some more very relevant information on endocrine effects of some very commonly prescribed psych medications–this time, elevated prolactin levels, prolactinomas, and risk of osteoporosis or osteopenia–and thought I would quickly post some links to research. No matter what is causing the elevated prolactin levels, the health effects are the same.

SSRIs and Osteoporosis – “After adjustment for many potential covariates, daily SSRI use was associated with substantially increased risk of incident clinical fragility fracture (hazard rate, 2.1; 95% confidence interval, 1.3-3.4). Daily SSRI use was also associated with increased odds of falling (odds ratio, 2.2; 95% confidence interval, 1.4-3.5), lower bone mineral density at the hip, and a trend toward lower bone mineral density at the spine. These effects were dose dependent and were similar for those who reported taking SSRIs at baseline and at 5 years’ follow-up.”

Pharmacological causes of hyperprolactinemia – Antipsychotics/neuroleptics, “Antidepressant drugs with serotoninergic activity, including selective serotonin reuptake inhibitors (SSRI), monoamine oxidase inhibitors (MAO-I) and some tricyclics, can cause hyperprolactinemia.”

Prolactinomas in adolescents : persistent bone loss after 2 years of prolactin normalization – Bone loss from high prolactin levels. “Adolescents with prolactinoma have osteopenia or osteoporosis, a finding that strengthens the need for a prompt diagnosis. Since normalization of PRL concentrations by dopamine agonist therapy is unable to restore the bone mass, other therapeutic approaches should be considered in order to prevent futher long-term problems.”

Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia – “Higher doses of medication were associated with increased rates of both hyperprolactinaemia and bone mineral density loss. Bone loss for the whole group was correlated with medication dose…high risk of developing reduced bone mineral density as a consequence of hyperprolactinaemia-induced hypogonadism”

Effects of prolactin and estrogen deficiency in amenorrheic bone loss.

Secondary amenorrhea: Don’t dismiss it as ‘normal’ – “A young or middle-aged patient who stops menstruating may be pregnant or have an underlying medical problem that, left undiagnosed, could cause obesity, sexual dysfunction, infertility, osteoporosis, endometrial hyperplasia, or endometrial cancer. [some not from prolactin--U.] Yet clinicians too often dismiss secondary amenorrhea as a ‘normal’ result of a mental disorder or psychotropic.” Mentioned: antipsychotics, SSRIs.

High Prolactin Levels More on mechanisms, FSH and LH.

From Galactorrhea to Osteopenia: Rethinking Serotonin–Prolactin Interactions – How this might work, specifically with SSRI antidepressants.

Risperdal Can Have Troubling Side Effects in Boys – “growth of breasts in some male patients…Two of the boys he represents required mastectomies…Risperdal’s label mentions the possibility of elevated prolactin levels and also gynecomastia, growth of breasts in boys and men.”

Psychopharmacology: Galactorrhea and Gynecomastia in a Hypothyroid Male Being Treated With Risperidone – [milk production] “had a prolactin level of 48.2 ng/mL after only two weeks of risperidone” While “Normal prolactin levels in men are typically less than 15 ng/mL.”#

Galactorrhea in a 14-Year-Old Girl – “After infancy, galactorrhea is usually medication-induced and can occur in either males or females….Inducing medications include antipsychotics, antidepressants”

Female Puberty: Clinical Implications for the Use of Prolactin-Modulating Psychotropics – ” Pubertal girls are especially vulnerable to medication-associated adverse events.”

Non-puerperal lactation associated with antidepressant drug use – Galactorrhea.

Quantifying the 5-HT1A agonist action of buspirone in man – “buspirone possesses D(2) antagonist and 5-HT(1A) agonist activity, both of which will result in the release of prolactin…dual action…produced a robust prolactin response” Any drug with either of these actions will stimulate prolactin.

Osteoporosis after combined use of a neuroleptic and antidepressants – “spontaneous rib fracture in a female patient (age 52) taking neuroleptics (mainly risperidone), antidepressants (mainly sertraline), and anxiolytics (mainly lorazepam). At the time of the fracture a severe osteoporosis and a strongly enhanced plasma prolactin level (117 ng/ml; normal values: 3–24 ng/ml) were detected….attention should be paid to bone mineral density loss in depressed patients taking a combined therapy of atypic antipsychotics and antidepressants. “

Fluoxetine [Prozac], but not Tricyclic Antidepressants, Potentiates the 5-Hydroxytryptophan-Mediated Increase in Plasma Cortisol and Prolactin Secretion in Subjects with Major Depression or with Obsessive Compulsive Disorder – Tricyclics “just” affect prolactin through D(2) antagonist action, the same as antipsychotics/neuroleptics.

A possible effect of amisulpride on a prolactinoma growth in a woman with borderline personality disorder – “prolactinoma probably induced by amisulpride”

Effect of Risperidone on Prolactinoma Growth in a Psychotic Woman – “[R]isperidone use was found to correspond with an increase in the size of a prolactinoma and prevented the return of serum prolactin level to baseline.” In other cases, “[L]ong-term maintenance doses of neuroleptics [lead to prolactin]…ranges of up to 19 times the mean baseline values (4). It has been reported that a girl with schizophrenia developed prolactinoma while being treated with thioridazine (5). Thioridazine may have also enhanced prolactinoma growth as manifested by an increase in serum prolactin concentration and deterioration of visual fields in a man with schizophrenia “

The effect of neuroleptics on prolactinoma growth in a Jordanian schizophrenic girl – “developed prolactinoma while being treated with neuroleptics”

Prolactinomas in children and adolescents–consequences in adult life. – “menstrual irregularities, infertility, short stature, osteopenia and/or osteoporosis”

Atypical antipsychotics and pituitary tumors: a pharmacovigilance study.

RAPID WEIGHT GAIN, AT LEAST IN SOME WOMEN, IS AN EXPRESSION OF A NEUROENDOCRINE STATE CHARACTERIZED BY REDUCED HYPOTHALAMIC DOPAMINERGIC TONE – “associated with galactorrhea and increased prolactin levels”

Increased body weight associated with prolactin secreting pituitary adenomas: weight loss with normalization of prolactin levels.

Weight gain and hyperprolactinemia in schizophrenic patients treated during twelve months with long acting risperidone – “link between weight gain and long term hyperprolactinemia”

Emotional Aspects of Hyperprolactinemia – “prolactin acts upon the central nervous system and variations in its concentrations do affect mood, emotions and behavior”

Depression hostility and anxiety in hyperprolactinemic amenorrhea.

And I had to include:
The Role of Prolactin in Mammary Cancer

Hyperprolactinaemia and Antipsychotic Therapy in Schizophrenia: Antipsychotics and Hyperprolactinaemia-Related Adverse Effects – “prevalence of menstrual disturbances is 15-50%”, bone density, breast cancer

Neuroleptic-induced prolactin level elevation and breast cancer: an emerging clinical issue.

Breast Carcinoma in Patients Receiving Neuroleptic Therapy

Obviously, not everyone will experience these adverse effects, but people should be aware that it’s a possibility when taking antipsychotics or antidepressants. Some atypical antipsychotics have to carry warnings about this now, but even though antidepressants can also increase prolactin levels, these risks are not considered as often when they’re prescribed.

Risks seem to be higher among kids, which is not surprising given their systems are still developing; the same holds true for other metabolic changes causing massive weight gain, insulin resistance, and eventually Type 2 diabetes (which I also got, in my early 20s). Antidepressants will also directly cause insulin resistance, weight gain, and an increased risk of developing diabetes dependent on dosage and length of treatment. There has not been adequate research into these medications’ effects on kids’ developing endocrine systems.

Maybe I’d better mention again that I am not trying to tell anyone what they should do. I’m all for real informed choice. Without good information about both risks and benefits, people just don’t have the freedom to evaluate the options available to them so they can make informed choices.

As I described in an earlier post, I was diagnosed with a fast-growing pituitary prolactinoma in 1990–at 15–after a little more than a year on Prozac. They are rare in kids that age, and almost never grow that quickly. Bromocriptine did not work, besides making me sick, and the tumor was removed in early 1992; from a tiny speck on the initial MRI scan, it had grown enough that they would not have even tried transsphenoidal surgery had they known how big it was. Still, after surgery, I continued to experience unpleasant and disabling symptoms of elevated prolactin (including amenorrhea and hot flashes) for many years while continuing on other medications which will elevate prolactin levels. This only turned around after I got off the medications several years ago, and I have lost nearly 100 lbs. from my top weight without trying. While my prolactin and cortisol levels were really high, I just kept packing on weight no matter what kind of exercise I did, and no matter how little or what kinds of things I ate. Ironically, I have also experienced less anxiety and depression, which makes complete sense given the effects of too much prolactin and cortisol on people’s moods. Good thing I had huge, dense bones starting out, but I am still concerned about rebuilding bone density; it was never mentioned, much less tested. As for other longterm effects from having the tumor so young, “short stature” is not obvious, but I topped out at 5’8″ instead of the (not unusual in the family) 6’3″ or 6’4″ projected when I was a kid! Then again, my biodad is about 5’7″, so it’s hard to tell. I may well be infertile; though the possibility/probability has been raised repeatedly, this has never been tested either, and I am not about to experiment to find out!

If there were any doubts about what was causing this, I took Paxil again for several months about a year ago; my periods promptly stopped, and I got galactorrhea again. Things evened out again after I stopped taking it.

None of these prolactin effects were connected to the medications in the ’90s, but research has caught up by now.

It’s a shame that a lot of doctors are still unfamiliar with this research, so that people have to look for explanations for their endocrine symptoms online, but hopefully getting this info out can help somebody else from having to go through similar themselves!

Some of the antidepressants which might carry these risks (from here): Celexa (citalopram), Lexapro (escitalopram oxalate), Luvox (fluvoxamine), Paxil (paroxetine), Prozac (fluoxetine), Zoloft (sertraline), Cymbalta (duloxetine), Effexor (venlafaxine), Pristiq (desvenlafaxine), Serzone ( nefazodone), Buspar (buspirone), Nardil (phenelzine), Parnate (tranylcypromine), Adapin (doxepin), Sinequan (doxepin), Desyrel (trazodone), Anafranil (clomipramine), Elavil (amitriptyline), Endep (amitriptyline), Ludiomil (maprotiline), Norpramin (desipramine), Pertofrane (desipramine), Surmontil (trimipramine), Tofranil (imipramine), Vivactil (protriptyline). Based on the Pharmacological causes of hyperprolactinemia info, I ran a quick search on each tricyclic antidepressant in the list, and all–not “some”–will elevate prolactin levels, through the same D(2) antagonist action as antipsychotics/neuroleptics (also why both types of medication are sedating).

It appears that Remeron (mirtazapine) and Wellbutrin (bupropion) “are prolactin neutral”, less likely to elevate prolactin levels.

Neuroleptics / antipsychotics (from here): Droperidol (Droperidol), Chlorpromazine (Thorazine), Clozapine (Clozaril), Fluphenazine (Prolixin), Haloperidol (Haldol), Loxapine (Loxitane), Mesoridazine (Serentil), Molindone (Moban), Olanzapine (Zyprexa/Zydis), Paliperidone (Invega), Perphenazine (Trilafon), Pimozide (Orap), Prochlorperazine (Compazine), Quetiapine (Seroquel; Seroquel XR), Risperidone (Risperdal; Risperdal Consta), Thiotixene (Navane), Thioridazine (Mellaril), Trifluoperazine (Stelazine), Ziprasidone (Geodon), the combination Olanzapine/Fluoxetine (Symbyax). These medications are also commonly prescribed now for depression, bipolar disorder, agitation among autistic people, Tourette’s Syndrome, and other things.

Apparently, Aripiprazole (Abilify) is less likely to send prolactin sky-high; “Dystonia, QTc abnormalities, prolactin and cholesterol increase were less frequent” than with olanzapine or risperidone (two of the worst offenders for metabolic problems). Here’s a variety of other abstracts showing far less prolactin elevation from aripiprazole.

OK, this post did not stay a quick rundown of links. ;) But it’s important stuff, which isn’t talked about nearly enough.

3 Comments leave one →
  1. January 4, 2012 3:31 pm

    Hmmm, interesting. Here’s my story, I think I’ve been fighting a low grade depression for a couple of years (dysthimia). But when you have dysthimia you tend to not think there’s anything wrong with you it’s just your “normal”. My period started to become erratic, I thought related to age (37). Anyways, I had a bad year made a few dumb decisions, which included using MDMA exactly 3 times. After the second use I had an abnormal test result for elevated prolactin. After my third use and a whole lot of stress, I feel into a full blown depression. Started taking Pristiq, an SNRI.

    Mood almost back to normal. Period normal. Prolactin Normal. Weird eh?

    • urocyon permalink*
      January 5, 2012 6:09 pm

      Glad that’s been working for you. :) Reactions to medications can be very different, depending on the individual’s system. One of the tricky things with recognizing side effects sometimes, especially dealing with some medical professionals who seem to expect everyone to respond the same.

  2. January 21, 2012 6:56 pm

    Thank you for your collection of articles. I have been wondering about the association of bone density loss and high prolactin levels. I have experienced galactorrhea since early puberty (14 or so) and never thought anything of it. It was normal for all I knew! I was only diagnosed at age 31 when we experienced trouble conceiving. Tah-dah, macroadenoma. I was treated with Bromocryptine (high dose) throughout pregnancy and was able to have two children. Now that we are done having children my gynecologist assured me that I can use my high prolactin levels as birth control… no pill, just using no Bromocryptine. He said there was no danger of bone density loss. Hah! That did not make sense to me… and thanks to you I am finding some articles to back up my impression. After reading them I really wish I had been diagnosed MUCH earlier in life.

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