Archives of Physical Medicine and Rehabilitation
Volume 89, Issue 6 , Pages 1090-1096, June 2008

The Impact of Female Reproductive Function on Outcomes After Traumatic Brain Injury

Presented to the American Academy of Physical Medicine & Rehabilitation, November 2006, Honolulu, HI.

  • David L. Ripley, MD, MS

      Affiliations

    • Craig Hospital, Englewood, CO
    • Department of Physical Medicine and Rehabilitation, University of Colorado at Denver and Health Sciences Center, Denver, CO.
    • Corresponding Author InformationReprint requests to David L. Ripley, MD, MS, CNS Medical Group, Craig Hospital, 3425 S Clarkson, Englewood, CO 80113
    • ,
  • Cindy Harrison-Felix, PhD

      Affiliations

    • Craig Hospital, Englewood, CO
    • Department of Physical Medicine and Rehabilitation, University of Colorado at Denver and Health Sciences Center, Denver, CO.
    • ,
  • Melissa Sendroy-Terrill, MA

      Affiliations

    • Craig Hospital, Englewood, CO
    • ,
  • Christopher P. Cusick, BA

      Affiliations

    • Craig Hospital, Englewood, CO
    • ,
  • Amy Dannels-McClure, RN, ND

      Affiliations

    • Craig Hospital, Englewood, CO
    • ,
  • Clare Morey, MA, SLP-CCC

      Affiliations

    • Craig Hospital, Englewood, CO

Article Outline

Abstract 

Ripley DL, Harrison-Felix C, Sendroy-Terrill M, Cusick CP, Dannels-McClure A, Morey C. The impact of female reproductive function on outcomes after traumatic brain injury.

Objectives

To determine the impact of traumatic brain injury (TBI) on female menstrual and reproductive functioning and to examine the relationships between severity of injury, duration of amenorrhea, and TBI outcomes.

Design

Retrospective cohort survey.

Setting

Telephone interview.

Participants

Women (N=30; age range, 18–45y), between 1 and 3 years postinjury, who had completed inpatient rehabilitation for TBI.

Interventions

Not applicable.

Main Outcome Measures

Data collected included menstrual and reproductive functioning pre- and postinjury, demographic, and injury characteristics. Outcome measures included the Glasgow Outcome Scale–Extended (GOS-E), the Mayo-Portland Adaptability Inventory–4 (MPAI-4), and the Medical Outcome Study 12-Item Short-Form Health Survey, Version 2 (SF-12v2).

Results

The median duration of amenorrhea was 61 days (range, 20–344d). Many subjects' menstrual function changed after TBI, reporting a significant increase in skipped menses postinjury (P<.001) and a trend toward more painful menses (P=.061). More severe TBI, as measured by the duration of posttraumatic amnesia, was significantly predictive of a longer duration of amenorrhea (P=.004). Subjects with a shorter duration of amenorrhea scored significantly better on the SF-12 physical component subscale (P=.004), the GOS-E (P=.05), and the MPAI-4 participation subscale (P=.05) after controlling for age, injury severity, and time postinjury.

Conclusions

The severity of TBI was predictive of duration of amenorrhea and a shorter duration of amenorrhea was predictive of better ratings of global outcome, community participation, and health-related quality of life postinjury.

Key Words: Amenorrhea, Brain injuries, Outcome assessment (health care), Rehabilitation

 

INFORMATION REGARDING the impact of traumatic brain injury (TBI) on women remains limited, including information regarding changes in reproductive and sexual functioning, psychosocial adjustment, and outcomes.1 Additionally, women with disabilities in general are far less likely to receive adequate routine medical care than the able-bodied population.2 Poor understanding of TBI's impact on physiologic functioning naturally exacerbates this problem for women after TBI.

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Menstrual Irregularities After Critical Illness 

The female reproductive system is exquisitely sensitive to stress,3 and hypogonadotrophic hypogonadism or abnormal functioning of the ovaries because of insufficient levels of supporting hormones is a common finding in critical illness.4 Bing-You and Spratt5 showed that serum estrogen levels decrease after stress. This stress response is often associated with amenorrhea, or the absence of menstrual periods. Menstrual cycle abnormalities have been documented in a number of neurologic conditions, including spinal cord injury (SCI),6 cerebrovascular accident,7 and brain tumor.8 These abnormalities are generally attributed to the stress response.3 Our clinical observation of females who have sustained a TBI reveals that abnormalities in menstrual cycles frequently occur in this population as well. However, the incidence and duration of amenorrhea has not been previously documented in this population.

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Endocrine Dysfunction After TBI 

Endocrine disorders are present in a significant percentage of both men and women after TBI.9, 10, 11, 12, 13, 14 Numerous hormonal disturbances have been documented after TBI,9, 10, 12, 15, 16, 17, 18, 19 and the incidence of endocrine dysfunction in patients with a moderate to severe TBI has been reported to be as high as 50% 1 year postinjury.9 Although the severity of injury is associated with the degree of endocrine dysfunction during the acute period of brain injury recovery, the relationship between chronic endocrinopathy and injury severity is less well established.9, 10, 12, 13 Despite numerous studies documenting the presence of hormonal alterations after TBI, the relationship between injury severity, prognosis, and endocrine dysfunction is not clear.20

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Menstrual Irregularities May Be Caused by Hypopituitarism After TBI 

Amenorrhea is known to be associated with pituitary dysfunction. In females with pituitary tumors, menstrual irregularities are the most common initial symptom.8 The location of the pituitary gland and hypothalamus on the floor of the calvarium makes these structures particularly susceptible to trauma, thus suggesting a potential common pathway for brain injury, pituitary dysfunction, and amenorrhea. A single-case study of a young woman who presented with amenorrhea after severe TBI was found to have traumatic disruption of the infundibulum (the stalk connecting the pituitary gland to the hypothalamus). This case report21 clearly linked amenorrhea with a pituitary injury after TBI. Again, although evidence of pituitary dysfunction after TBI is clinically well recognized, what remains unclear is whether amenorrhea occurs simply because of the stress response, or whether other hormonal factors also significantly contribute to this problem.

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Sex Differences in Outcomes After TBI 

It has long been recognized that there are subtle sex differences in cognitive performance and neural structures in humans. There is now a growing body of evidence suggesting that women have better functional outcomes and lower mortality rates than men after TBI.1, 22 Groswasser et al22 found that women had better outcomes than men after TBI. Wagner et al23 additionally found differences in markers of oxidative damage in the cerebral spinal fluid between men and women, suggesting sex differences in the physiologic response to injury. These sex differences are frequently attributed to female gonadal steroid hormones, especially estrogen and progesterone.22, 24 Admittedly, sex differences in outcomes after brain injury is a subject of controversy. Other studies have not found sex differences in mortality25, 26 or performance on neuropsychologic tests.27, 28 Some studies have shown females to have increased reports of symptoms29 and worse overall outcomes.30, 31

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Objectives 

The objectives of this study were (1) to compare the course of menstrual and reproductive functioning in women before and after TBI, (2) to determine if the severity of TBI is associated with the duration of amenorrhea, and (3) to determine if the duration of amenorrhea after TBI is associated with outcomes.

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Methods 

Participants 

This study was approved by the Investigational Review Board for Craig Hospital and funded by the Colorado Traumatic Brain Injury Trust Fund Research Program. Sixty former female patients who sustained a TBI and were between 1 and 3 years postinjury (November 2001–April 2005) at the time of the study were identified. All participants were between the ages of 18 and 45 inclusive at the time of injury. Exclusion criteria for this study included (1) postmenopausal for any reason before injury; (2) previous TBI, SCI, or a history of psychiatric, cerebrovascular, endocrine, or bleeding disorder; (3) amenorrhea before TBI for a duration of greater than 6 months (excepting pregnancy); (4) pregnant or lactating at the time of injury; or (5) received exogenous glucocorticoids. Medical record abstraction identified 52 women who met study criteria.

Thirty participants ultimately consented and took part in a 1-time telephone interview that documented pre- and postinjury reproductive cycle functioning and outcome measures. Proxy interviews were conducted with the patient's primary caretaker for those participants who were cognitively unable to complete the interview (10%). After the interview, demographic and injury severity information (table 1) was obtained from the participant's rehabilitation medical records. Variables abstracted from medical records included age, years postinjury, length of stay in the rehabilitation hospital, Glasgow Coma Scale (GCS) score,32 length of posttraumatic amnesia (PTA), days of unconsciousness, presence of basilar skull fracture, race, marital status, education level, and employment status at the time of injury. Emergence from PTA was indicated by scores of 76 or greater on 2 consecutive administrations of the Galveston Orientation and Amnesia Test.33

Table 1. Demographic and Clinical Characteristics (N=30)
CharacteristicsFrequencies
Mean age at injury ± SD (y)28.0±8.9
Mean years postinjury at interview ± SD2.7±0.9
Initial GCS classification (%)
Mild20.0
Moderate13.3
Severe60.0
Unknown6.7
Days of PTA
Mean ± SD42.4±43.1
Median21.0
25th percentile10.0
75th percentile67.5
Basilar skull fracture (%)
No40.0
Yes43.3
Unknown16.7
Race (%)
White93.3
Hispanic origin6.7
Education level (%)
<High school10.0
High school/GED16.7
Some college43.3
≥Bachelor's degree30.0
Days of amenorrhea
Mean ± SD83.2±71.2
Median60.5
25th percentile32.5
75th percentile100.5

Abbreviations: GCS, Glasgow Coma Scale; GED, general educational diploma; PTA, posttraumatic amnesia; SD, standard deviation.

Measures 

Menstrual and reproductive functioning data 

A questionnaire was designed to gather information about premorbid menstrual functioning and reproductive history as well as current menstrual functioning and reproductive issues. Questionnaire items reviewed topics presented in table 2 and questions pertaining to fertility. Details about prior reproductive history were also obtained including prior pregnancy, delivery, miscarriage, or fertility treatments. It was our experience that all subjects answered questions candidly.

Table 2. Pre- and Postinjury Menstrual Functioning
VariablePreinjuryPostinjuryP
Birth control used (%) .63
No50.056.7
Yes50.043.3
Type of birth control used (%) .50
Nonhormonal13.330.8
Hormonal86.769.2
Average no. of days between periods .29
Mean35.429.6
Median30.030.0
SD29.16.6
Minimum21.014.0
Maximum180.045.0
Ever skip periods (%) <.00
No76.710.0
Yes23.390.0
No. of periods missed .07
Mean2.86.0
Median0.03.0
SD4.27.3
Minimum0.00.0
Maximum12.029.0
No. of days periods last .26
Mean5.74.8
Median4.04.0
SD4.91.4
Minimum3.03.0
Maximum30.09.0
How heavy are periods (1–5) >.10
Mean2.82.8
Median3.03.0
SD0.70.8
Minimum1.01.0
Maximum4.04.0
How painful are periods (0–10) .06
Mean2.12.9
Median2.03.0
SD2.02.6
Minimum0.00.0
Maximum7.010.0
Mayo-Portland Adaptability Inventory–4 

The Mayo-Portland Adaptability Inventory–4 (MPAI-4)34 was designed to assist in the clinical evaluation of people during the postacute period after acquired brain injury. The MPAI-4 has 29 items that represent the range of physical, cognitive, emotional, behavioral, and social problems that people may encounter after acquired brain injury. MPAI-4 items also provide an assessment of major obstacles to community integration that may result directly from acquired brain injury. The MPAI-4 has 3 subscales: ability, adjustment, and participation.

Glasgow Outcome Scale–Extended 

The Glasgow Outcome Scale–Extended (GOS-E)35 is an 8-level scale (range, dead to upper good recovery) that provides structured interview and scoring to assess global outcomes for people who have sustained a TBI. Compared with the GOS, the GOS-E has been shown to be more sensitive to change in mild to moderate TBI. Based on a sample of neurosurgical subjects, using 2 independent raters, interrater agreement was 78% when using the GOS-E structured interview.35 The GOS-E interview can be reliably conducted through telephone contact.36

Medical Outcome Study 12-Item Short-Form Health Survey, Version 2 

The Medical Outcome Study 12-Item Short-Form Health Survey, Version 2 (SF-12v2)37 is a valid and reliable measure of health-related quality of life (HRQOL). It is a 12-item subset of the SF-36v2 survey that measures the same 8 domains of health: physical functioning, role limitations because of physical health problems, bodily pain, general health, vitality (energy/fatigue), social functioning, role limitations because of emotional problems, and mental health (psychologic distress and psychologic well-being).38 The SF-12 yields a physical component summary (PCS) score and a mental component summary (MCS) score.

Statistical Analysis 

All data analyses were performed using SPSS.39,a Various analytic techniques were used to address each of the 3 study objectives.

To address objective 1, to compare the course of menstrual and reproductive functioning in women before and after TBI, relevant pre- and postinjury questionnaire items were compared by using McNemar tests and Wilcoxon signed-rank tests. McNemar tests were used for dichotomous data, whereas Wilcoxon signed-rank tests were used for categoric rank-order data and for continuous data. Nonparametric tests were chosen for continuous variables to address skewness in the data distributions. Alpha levels of .05 were used for both statistical tests.

To address objective 2, to determine if the severity of TBI is associated with the duration of amenorrhea, Kaplan-Meier survival curves were plotted to show differences in durations of amenorrhea among women with varying TBI severity levels. The Kaplan-Meier method is an actuarial technique for estimating time-related events (the survivorship function). Ordinarily, it is used to analyze death as an outcome. However, it may be used effectively to analyze time to an endpoint, such as return of menses. TBI severity levels were determined by using both GCS scores and durations of PTA for classification. Mantel-Cox log ranks tests were used to determine if observed differences were statistically significant when using an α level of .05. Additionally, Cox proportional hazards models were used to examine the relationship between the severity of injury and the duration of amenorrhea while controlling for age. The length of unconsciousness, presence of basilar skull fracture, and other radiologic findings were evaluated in a similar manner to determine if it was necessary to construct a multivariate model inclusive of all significant univariate predictors of duration of amenorrhea.

For objective 3, to determine if the duration of amenorrhea after TBI is associated with outcome while controlling for severity of injury, a frequency distribution for the duration of amenorrhea was generated to classify the durations into logical categories. Univariate analyses of covariance (ANCOVA) models were used to compare scores for each of the outcome measures among women with varying durations of amenorrhea. The ANCOVA models controlled for age, time postinjury, and severity of injury using the duration of PTA. The duration of PTA (in days) was unknown for 5 participants who had been discharged from inpatient rehabilitation while still in PTA. Consequently, data for these cases were recoded to reflect “emerged from PTA” at rehabilitation discharge rather than “ongoing PTA” to avoid missing data for a significant proportion of cases.

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Results 

Thirty women completed the 1-time telephone survey. Demographic and clinical characteristics are shown in table 1. The mean age of the sample was 28 years. The sample was primarily white (93.3%), single (66.7%), and highly educated, with 73.3% having completed at least some college. Ninety percent of the sample reported being either employed or a full-time student at the time of their injury. According to the GCS classification, 20% sustained a mild injury, 13.3% sustained a moderate injury, and 60% sustained a severe injury, with 2 women whose GCS scores were unknown. The mean duration of amenorrhea for the sample was 83.2 days, with a median ± standard deviation of 60.5±71.2 days.

Objective 1: To Compare the Course of Menstrual and Reproductive Functioning in Women Before and After TBI 

Table 2 shows the differences between preinjury and postinjury menstrual functioning. Using an α level of .05, significant differences were identified for only 1 of the 8 comparisons made. Twenty-three percent of the participants reported skipping periods in the year before injury versus 90% postinjury. This difference was highly significant (P<.001). Statistical analysis also indicated 2 trends that are noteworthy. First, participants reported a higher number of skipped periods postinjury than they did preinjury (postinjury median, 3.0; preinjury median, 0.0; P=.065). Second, on a scale of 0 to 10, participants reported 1-point increases on average for the severity of pain experienced during menses (postinjury median, 3.0; preinjury median, 2.0; P=.061).

For the 9 items that compared preinjury and postinjury fertility, no appreciable differences were identified, largely because of the small proportion of participants who reported ever becoming pregnant (n=4).

Objective 2: To Determine if the Severity of Injury is Associated With the Duration of Amenorrhea 

Participants were classified into 2 categories based on their GCS scores: severe (3–8) and mild or moderate (9–15). Mild (13–15) and moderate (9–12) cases were collapsed into 1 common category because of the small number of participants in each group (n=6, n=4, respectively).

Kaplan-Meier survival curves indicated durations of amenorrhea between 20 and 114 days for the mild and moderate group, with resolution of amenorrhea after 61 days for 50% of the participants. For the severe group, durations of amenorrhea ranged between 24 and 344 days, with resolution of amenorrhea (also) after 61 days for 50% of the participants (fig 1). Differences in durations of amenorrhea between the 2 groups were not statistically significant per Mantel-Cox log ranks tests (P=.251).

Similar analyses were repeated using duration of PTA as the severity of injury indicator. Again, participants were classified into 2 categories: severe (≥8d) and moderate (2–7d). No participant in the sample had a duration of PTA less than 2 days. Durations of amenorrhea ranged between 20 and 73 days for the moderate group and were between 24 and 344 days for the severe group. Amenorrhea had resolved after 37 days for 50% of the participants in the moderate group compared with 75 days postinjury for 50% of the participants in the severe group (fig 2). Differences in durations of amenorrhea between the 2 groups were statistically significant per Mantel-Cox log-rank tests (P=.027).

Cox proportional hazards models were used to determine if the severity of injury was predictive of the duration of amenorrhea while controlling for the woman's age. The duration of PTA was used as the primary injury severity measure because it was found to be associated with the duration of amenorrhea in the previous analysis.

Analysis using the duration of PTA, age at interview, and the interaction term for age and PTA indicated that PTA was the only significant predictor of the duration of amenorrhea (age, P=.306; PTA, P=.028; age by PTA, P=.079). Other clinical indicators of injury severity such as the GCS score, length of loss of consciousness (LOC), and presence or absence of a basilar skull fracture were examined in the same manner to determine if it was necessary to construct a multivariate model. No other clinical indicators of severity were found to be significant predictors of the duration of amenorrhea (GCS score, P=.255; length of LOC, P=.372; basilar skull fracture, P=.85). Based on these findings, a final model was derived by using the duration of PTA (in days, recoded as described earlier) as the only predictor. Results from the final model showed that the duration of PTA was highly predictive of the duration of amenorrhea (Exp(B)=.982, P=.004), indicating approximately 2% increases in durations of amenorrhea for every 1-day increase in the duration of PTA.

Objective 3: To Determine if the Duration of Amenorrhea After TBI is Associated With Outcome 

For these analyses, the frequency distribution of duration of amenorrhea was used to classify the durations into 3 categories: short (20–37d), medium (53–96d), and long (114–344d). Long-term outcome measures included the SF-12v2 PCS and MCS health summary measures; the GOS-E; the MPAI-4 ability, adjustment, and participation subscales, and total score. Univariate ANCOVA models were used to compare scores for each outcome measure between participants with short, medium, and long durations of amenorrhea. Covariates included age at interview, years postinjury at interview, and duration of PTA. PTA was used in this analysis as the measure of injury severity because it was the only severity measure associated with the duration of amenorrhea. Comparisons were made by using the long (114–344d) duration of amenorrhea group as the reference category. Preliminary models were constructed entering all possible interaction terms to check for significant interactions among the covariates. No significant interactions (P<.05) were identified so final models were constructed without entering the interaction terms.

Results are shown in table 3. Each row of the table represents a separate ANCOVA model, one for each of the 7 outcome measures listed in column 1. Symbols are used to indicate the overall significance level for tests of between-subjects effects for the duration of amenorrhea associated with each of the outcomes listed in column 1. Columns 2 to 5 represent the parameter estimates for the short (20–37d) and the medium (53–96d) duration of amenorrhea groups in relation to the long (114–344) duration of amenorrhea group (reference category). Statistically significant results are depicted in bold typeface.

Table 3. Associations Between Long-Term Outcomes and the Duration of Amenorrhea
MeasureDuration of Amenorrhea⁎
Short (20–37d) (n=8)†Medium (53–96d) (n=12)†
BPBP
SF-12 PCS‡17.5.00417.5.001
SF-12 MCS−7.2.193−5.5.262
GOS-E§2.1.0241.8.028
MPAI-4 ability−8.9.281−15.4.044
MPAI-4 adjustment1.5.818−4.4.457
MPAI-4 participation§−20.7.061−24.2.016
MPAI-4 total−5.8.317−10.7.046

NOTE. Boldface denotes significance at P<.05.

⁎The duration of amenorrhea, while controlling for age, severity of injury (PTA), and time postinjury.

†Reference group: a long duration of amenorrhea (114–344d); n=7.

‡P<.01.

§P<.05 (overall ANCOVA model significance).

Statistically significant differences (P<.05) in outcomes were identified for 3 of the 7 outcomes measures examined based on participant's durations of amenorrhea. These were the SF-12 PCS score, the MPAI-4 participation subscale, and the GOS-E.

Tests of between-subjects effects for duration of amenorrhea were statistically significant for the SF-12 PCS (P=.004). Parameter estimates indicated that SF-12 PCS scores were 17.5 points better for women with both short and medium durations of amenorrhea compared with women with long durations (given similar ages, durations of injury, severity levels).

Tests of between-subjects effects for duration of amenorrhea were statistically significant for the GOS-E (P=.05). Parameter estimates showed that women with short durations of amenorrhea scored 2.1 points better than women with long durations. Similarly, women with medium durations scored 1.8 points better than women with long durations (given similar ages, durations of injury, and severity levels).

Tests of between-subjects effects for duration of amenorrhea were statistically significant for the MPAI-4 participation subscale (P=.049), yet parameter estimates were statistically significant only for the medium duration of amenorrhea group (P=.016) but not for the short-duration group (P=.061). Results showed that women with medium durations scored 24.2 points better on the MPAI-4 participation subscale than women with long durations. And, although it was nonsignificant, there was a trend suggesting that women with short durations scored 20.7 points better on average than women with long durations, given similar ages, durations of injury, and severity levels.

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Discussion 

To our knowledge, this is the first study investigating the effects of TBI on female reproductive cycle functioning and subsequent outcomes. The median length of amenorrhea in this sample was 61 days, which is consistent with clinical observations of women after TBI. There was a significant change in menstrual functioning after injury compared with preinjury, with significantly more women reporting that they skipped menses after TBI than before injury. However, the postinjury time frame includes those that experienced amenorrhea. Trends were also reported in the number of missed menses and the intensity of pain experienced during menses.

The duration of amenorrhea was found to be associated with the severity of injury as measured by PTA. Although this finding was not supported with the GCS score as the indicator of severity of injury, it is believed that many factors may affect the reports of initial GCS score at the time of injury, such as alcohol use, more frequent use of sedatives in the field, and inconsistent reporting of GCS data. Prior research40 has suggested that PTA has a greater correlation with long-term outcomes after TBI than GCS score, although collecting PTA data is more time-consuming and difficult for medical treatment facilities. However, because all participants completed inpatient rehabilitation at the same facility in this study, where PTA data are consistently recorded as part of the treatment protocol, it is believed that this is the best true indicator of the severity of injury in this study. The duration of PTA was found to be highly predictive of duration of amenorrhea in this study, indicating a robust relationship, showing that more severe injury results in a longer duration of amenorrhea.

The most intriguing finding in this study was that the duration of amenorrhea was found to be associated with outcomes after TBI after controlling for the severity of injury, age, and time postinjury. Subjects with longer durations of amenorrhea were found to have worse scores on measures of HRQOL, global outcome, and community participation after TBI. Although admittedly controversial, this finding is consistent with the growing body of literature that attributes sex differences in outcomes and mortality rates after neurologic injury to female gonadal steroid hormones, in particular, progesterone and estradiol-17β.41 If the menstrual dysfunction after TBI is associated with pituitary dysfunction, which may also result in lower levels of the potentially neuroprotective female gonadal steroids, then a physiologic explanation for the association between the menstrual dysfunction and outcome becomes apparent.

Study Limitations 

This study is not without limitations. This study was cross-sectional in nature, and participants were interviewed anywhere between 1 and 3 years postinjury. Furthermore, the study relied on subjects' and their family's reports for information. Because these women had sustained brain injuries, the accuracy of information may be in question. Additionally, for those women who were unable to report data themselves, immediate caregivers were relied on to provide information. These caregivers may not have had reliable information of menstrual functioning, particularly of that before injury. Furthermore, this study has a small number of subjects drawn from a single center. It should be noted with this sample size and the number of statistical comparisons performed that a significant finding could occur just by chance. This study ideally should be replicated with a larger sample size drawing from multiple centers with a wider geographic representation. However, the robust findings even with such a small sample are strong evidence to support the conclusions of the study. Last, although the effect of amenorrhea on outcomes in this study has been attributed to hormonal dysfunction, no serum hormonal assessment was performed. This is currently being piloted in a follow-up study being performed at Craig Hospital.

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Conclusions 

The severity of TBI was predictive of the duration of amenorrhea after TBI. Additionally, a longer duration of amenorrhea was predictive of poorer global outcome, ratings of participation, and HRQOL postinjury, even after controlling for age, injury severity, and time postinjury. These findings may be caused by lower levels of circulating endogenous female gonadal steroids estrogen and progesterone, which have been implicated in numerous studies for neuroprotection and neuroregeneration. Women reported significant changes in menstrual cycles after TBI, supporting previous anecdotal clinical observations, with more women reporting missed menses after injury. Trends were also reported in the number of skipped periods and the pain experienced by women during their cycle after TBI.

As previously stated, this is an understudied area in the field of brain injury medicine. Directions for future research should include investigations into the impact of TBI on fertility, female sexual functioning, and recovery of hormonal function, including detailed assessment of the endocrine profiles of women as they are recovering from TBI. Additionally, longer-term assessment of menstrual functioning needs to be performed because many women have not recovered normal menstrual functioning even after 1 year. Last, detailed comparisons of TBI to other catastrophic injury categories (eg, SCI) need to be performed to assess the hypothesis that menstrual function changes after TBI are caused by pituitary dysfunction and not the stress response.

Ultimately, we hope that this line of inquiry leads to further research evaluating endocrine profile changes after TBI to clarify the impact of TBI on endocrine function and its relationship with outcomes and potentially new pharmacologic therapies to improve outcomes for both women and men after TBI.

Supplier

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Acknowledgment 

The opinions expressed herein are those of the authors and do not necessarily reflect the views of the Colorado Traumatic Brain Injury Trust Fund.

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 Supported by the Colorado Traumatic Brain Injury Trust Fund Research Program.

 No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the authors or upon any organization with which the authors are associated.

PII: S0003-9993(08)00170-6

doi:10.1016/j.apmr.2007.10.038

Archives of Physical Medicine and Rehabilitation
Volume 89, Issue 6 , Pages 1090-1096, June 2008

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