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LUPRON: MEMORY LOSS AND COGNITIVE
DYSFUNCTION
In February, 1992, three pharmacists reported the results of a telephone survey they conducted among 16 women who had taken a GnRH analogue, (not Lupron), over the previous 4 months.(1) The survey found that "56% reported some type of memory difficulty."(1) The survey was instituted after a 30-year-old woman reported short-term-memory loss approximately one month after she was prescribed a GnRH analogue. "Several days later, another patient reported a similar occurrence."(1) The pharmacists "conducted a MEDLINE search of possible memory impairment associated with GnRH analogs, estrogen deficiency, and menopause and were unable to retrieve any further documentation." When the pharmacists contacted the manufacturer, "a search of their computerized worldwide database" was able to locate ONLY 3 "reports of poor memory or memory loss that were possibly drug related." (1) This is quite a discrepancy from the pharmacists' findings of 56% reporting some type of memory difficulty. "The memory impairment was described by the women as memory loss, poor memory, forgetfulness, and concentration problems."(1) One woman (of the 16) "recounted her experience of driving down a street and stopping at a stop light but not being able to remember why she was at the stop light (she no longer drives alone)."(1)
In July, 1992, Dr. Andrew Friedman and colleagues reported memory loss in the medical literature. They stated that "two of the most disturbing adverse effects experienced by women receiving Leuprolide Acetate were depression and short-term memory loss." (2)
In 1993, Dr. Varney and colleagues reported the effects of Lupron on 18 women taking Lupron for infertility treatment.(3) Dr. Varney decided "to focus on possible problems as reported by prior patients." (3) According to Dr. Varney, patients regularly reported "poor memory and or clumsiness" on Lupron and "of particular interest were memory and coordination, as these were commonly observed patient complaints." (3)
Dr. Varney found that "a significant proportion of women, more than half in some cases, showed significantly worse performance on one or more memory tests while on leuprolide acetate. When memory test performances were combined, a substantial majority of the patients [72%] showed difficulty with memory while on leuprolide acetate."(3) (See table below) "Some individuals showed significant cognitive deficits" while on Lupron "particularly in the area of memory, fine motor coordination and two-point discrimination."(3) Dr. Varney also found that 50% of the women showed a 42.7% decline from baseline in fine motor coordination on Lupron, and, 22% of the women showed a 16.6% decline in gross motor performance.(3) (See table below)
                    Some Data Taken From Tests Performed by Dr. Varney et al.(3)
	
Test Performed While On Lupron:
	% of Women that
Declined on Lupron

	
	% Performance to Decline Lupron

	

	
	on Lupron   
	
Fine Motor Coordination:                                           50 %
	42.7 %
	
Gross Motor Coordination:                                        22 %
	16.6 %
	
Controlled Oral Word Association (COWA):               50%                                             
	18.7 %
	
Verbal Recall
	  
       56%
          44 %
	
5.0 %
23.5 %
	
Immediate-recall:
 Delayed-recall:

	
Judgment of Line Orientation:                                 33 %
	7.4 %
	
Digit Sequence Learning:                                           61 %
	22.5 %
	
Digit Symbol:
	          11%                  14.3%
	
Digit Span:                                                     |           28 %
	12 %
	
Free Verbal Recall & Digit Sequence                   72 % declined on at least 1 memory Learning:                                                                                      measure
	
Dr. Varney's study also found that 11% of the women taking Lupron showed more severe disturbances in cognitive function. (3) "In these cases, symptoms included episodic memory gaps, spells of aphasia, episodic problems with confusion, and brief dramatic changes in emotional tone. In addition, these women showed episodes of occasional sensory illusions in the auditory, visual, olfactory, or somatosensory spheres" of the brain.(3) "In each case the patient and others had noted significant lapses in their work and they were able to accomplish work for which they had no recollection."(3) "Memory gaps and other problems impaired them in activities of daily living, safe operation of motor vehicles, and vocational activities."(3) One of the 18 patients, in particular, had a drop in IQ from 135 to 117.(3)
	
In 1996, Dr. Newton and colleagues studied the effect of GnRH agonists on memory in 16 women. Dr. Newton concluded that memory functioning decreased during GnRH-a administration and "prospective memory was most affected." (4) Dr. Newton stated that "the mechanism by which memory is affected remains unclear but the hypothesis that psychological factors" that "could account for complaints was not supported." In addition, "impairment was not related to excessive health concerns or mood changes." According to Dr. Newton, 11% of the women without memory complaints prior to taking a GnRH-a continued to report memory problems 6 months after stopping the GnRH-a.(4)
Dr. Newton also concluded that "memory disruption may be a more common side effect of GnRH-a treatment than currently is recognized." "By the final week of treatment, women reported greater memory complaints than a community sample of similar age. He found that 75% experienced memory problems on a GnRH agonist. "Thirty-one percent [31%] had 'mild' complaints, (0 to 1 SD greater than the community mean), 25% had 'moderate' complaints (1 to 2 SD greater than the mean) and 19% had 'marked' complaints (greater than or equal to 2 SD greater than the mean)." Women also reported an increase in sour taste and numbness. (4)
The medical literature states that most people first experience cognitive disorders while on Lupron; not 5 or 10 years after stopping the drug. Yet, it took the medical community nearly 10 years to publish an article stating that Lupron even causes cognitive disorders. In 1993, Dr. Varney stated that "there was NO correlation between estradiol levels and test results on any test."(3) In 1993, Dr. Friedman stated that the mechanism by which short-term memory loss occurs is "unclear"(2)  In 1996, Dr. Newton stated that "the mechanism by which memory is affected remains unclear." From the above statements it is obvious that these doctors did not feel that the cognitive problems experienced by these women on Lupron were due to lack of estrogen and/or menopause.
The mechanism by which Lupron causes memory loss, episodic memory gaps, spells of aphasia, episodic problems with confusion, amnesia, difficulty thinking/concentrating, drops in IQ, problems with fine/gross motor coordination, and other cognitive problems, needs to be addressed. Most people occassionally forget a name, where they put their keys, or which aisle they parked their car at an amusement park. That is not what we are talking about with Lupron. Instead we are talking about pharmacists who stated that 1 of the 16 women they interviewed "recountered her experience of driving down a street and stopping at a stop light, but not being able to remember why she was at the stop light (she no longer drives alone)," (1) We are talking about a doctor who found that 1 of the 18 patients he studied had a drop in IQ from 135 to 117. (3)
	
We are talking about a doctor who found that 50% of the women he studied showed a 42.7% decline from baseline in fine motor coordination on Lupron, and, 22% of the women showed a 16.6% decline in gross motor performance.(3) We are talking about a doctor who reported that 11% of the women taking Lupron showed more severe disturbances in cognitive function. (3) We are talking about patients who had "significant lapses in their work and they were able to accomplish work for which they had no recollection." (3) Episodic memory gaps, spells of aphasia, episodic problems with confusion, amnesia, difficulty thinking/concentrating, drops in IQ, problems with fine/gross motor coordination, and other cognitive problems, have impaired many people on Lupron in activities of daily living, safe operation of motor vehicles, and vocational activities. This is more than occassionally forgetting a name, where you put you keys, or which aisle you parked your car in at an amusement park.
DEFINITIONS: (3)
Amnesia - Disturbance in memory manifested by total or partial inability to recall past experiences.
Aphasia - Impaired or absent communication by speech, writing, or signs, due to dysfunction of the brain centers in the dominant hemisphere.
	Cerebral - The brain; usually refers to the parts derived from the telencephalon and includes mainly the cerebral hemispheres (cerebral
cortex and basal ganglia).
Cognitive - A generic term embracing the quality of knowing, which includes perceiving, recognizing, conceiving, judging, sensing, reasoning, and imagining.
references
1.   Kortepeter C, Macmillan M, Ferrell R. Possible Short-Term Memory Loss Associated With Nafarelin Acetate. The Annals of Pharmacotherapy. February, 1992; 26: p. 169-171.
2.   Friedman AJ, Juneau-Norcross M, Rein MS. Adverse effects of leuprolide acetate depot treatment. Fertility & Sterility. 1993;59:2:448-450.
3.   Varney NR, Syrop C, Kubu CS, Struchen M, Hahn S, Franzen K. Neuropsychologic Dysfunction in Women Following Leuprolide Acetate Induction of Hyproestrogenism. Journal of Assisted Reproduction and Genetics, 1993; 10:1:53-57.
4.   Newton C, Slota D, Yuzpe AA, Tummon IS. Memory complaints associated with the use of gonadotropin-releasing hormone agonists: a preliminary study. Fertility & Sterility. 1996;5:6:1253-1255.
5.   Stedman's Medical Dictionary. Williams and Wilkins Company. Baltimore, 1979.
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