Keywords: Menopause, hormones, women’s health, two-factor analysis, HRT.
INTRODUCTION
The menopause is centered on the ovary and its in-built obsolescence. The events of the menopause start when the active ovary begins to fail and ends when the ovary lapses into inactivity. The duration of these events is variable. Stimulated by the pituitary, one follicle develops each month as a hormone-producing organ, with a lifespan of 28-days. Follicles continue to develop until they cease responding to stimuli from the pituitary. The 32-week fetus has approximately 7 million primordial follicles. At birth, the number drops to 2 million and by puberty only 300,000 to 300,800 remain. In adulthood, about 400 follicles will be responsible for the production of the ova and hormones. It is important to realize that during menopause women lose not only ovarian but also the brain’s response to hormonal triggers. For example, in menopause, the brain no longer responds to estrogen and /or luteinizing hormone (LH).
Menopausal women become deficient in multiple hormones such as estrogen, progesterone, testosterone, and DHEA1-6 with increases in LH, follicle stimulating hormone (FSH) and thyroid stimulating hormone (TSH).7-10 All of these hormones have individual as well as inter-related functions in the human body, including pulmonary, cardiovascular, GI and immunological functions. As increased life expectancy has changed the aging pyramid, clinical attention increasingly focuses on an identified decline in cognitive function due to the normal aging process.6,11 In fact, estrogen deficiency has been proposed as a cause of memory deficits in postmenopausal women.12 There are studies which suggest that LH increases after menopause with concomitant decline in cognitive performance.13 Chorionic gonadotropin receptors and LH occur in the brain.14 Thus, levels of LH and FSH may increase low-density lipoprotein receptor–related protein in the brain.12,15 Levels of FSH increase dramatically in women during and after menopause and can be lowered with estrogen therapy.12,16 Emerging evidence suggests that high TSH levels are associated with a 2-fold risk of cognitive decline as well as prevalence of anomalies in musculoskeletal systems.17-19
We hypothesized that females presenting with complaints related to menopause would have a number of associated hormonal changes relating specifically to both somatic and neurological symptoms. We used various statistical methods to examine the relationship of hormone levels and symptom complexes, including Pearson Product-Moment correlations, factor analysis, and ANOVA.
METHOD
Subjects
All female patients, who presented to a private clinic, at or approaching the typical age of menopause onset were examined. A total of 74 women were entered into the study, although every woman did not have all variables available for analysis. The mean age of the sample was 60.23 (SD = 9.21, range = 43-87]. Medical history, physical examination and laboratory analysis determined that 37 patients had uncomplicated age-related menopause, 11 had menopause related to gynecological surgery, 4 had gynecological organ disease without surgery, and 22 had menopause of ambiguous origin. Each patient filled out an approved IRB PATH informed consent and the IRB committee approved the study on May 20, 2009 [Registration # IRB00002334, Protocol #: LEXMEN001].
Design
All subjects underwent a thorough medical evaluation including a full screen for hormones including DHEA sulfate, estradiol, estrone, FSH, LH, pregnenolone, progesterone, free and total testosterone, and TSH obtained from an outside laboratory. A detailed medical history was obtained including information on the stage of menopause (not yet, undergoing, or through), origin of the menopause, and history of HRT. A Menopause Questionnaire (MQ) [Figure 1] was given to all women (n=74) following a preliminary screening. The quantitative section of the MQ consisted of 64 questions related to symptoms of menopause. Each symptom was rated on a Likert scale of frequency from 1 (never) to 5 (always). The total number of endorsed symptoms was calculated as a gross indicator of menopausal symptomatology. Mean values of the Likert ratings were also calculated within each of 12 domains of symptoms: Neurological, neuropsychiatric, neuropsychological, endocrine, pulmonary, musculoskeletal, gastrointestinal, cardiovascular, dermatological, genitourinary, immune, and gynecological. A grand mean of the Likert rating across all domains was also calculated. Patients were mailed follow-up MQs 6-months after their initial assessment.
Analyses
Pearson Product-Moment correlations were calculated between hormone levels and the 12 mean domain scores, the total number of endorsed systems, and the grand mean across all 64 questions of the MQ. A one-way analysis of variance was performed for the origin of menopause variable for each of the 12 symptom domains, with a Bonferroni correction of p<.004 required for significance. Given the large number of domains and likely high inter-correlations between them, a factor analysis with principal components extraction and varimax rotation was performed on the 12 mean domain scores. Factor scores were generated for each patient and entered into the correlation analysis with the hormone levels. A similar factor analysis was performed on the hormone levels to reduce redundancy of highly inter-correlated values. Regression analyses were performed to predict the symptom domain score factors from the 10 hormone levels and again using the hormone level factors. Similar analyses were performed on the follow-up MQ’s, but there were only 13 patients with follow-up data available.
Figure 1. Menopause questionnaire (MQ)
RESULTS
Pearson Product-Moment Correlations
Age did not correlate significantly with any of the hormone levels, symptom domains, total endorsed symptoms, or grand MQ mean. Significant correlations between hormone levels and the 12 MQ symptom domains appear in Table 1. DHEA correlated significantly with the genitourinary domain (r=.30, p<.05). Estrone had a negative correlation with the musculoskeletal domain (r=-0.43, p<.012). FSH correlated significantly with the pulmonary domain (r=-.29, p<.05). Pregnenolone correlated significantly with the genitourinary (r=.40, p<.006) and immunological (r=.38, p<.008) domains. Testosterone correlated significantly with the total number of symptoms endorsed (r=-.34, p<.016) but with none of the 12 MQ symptom domains. TSH correlated significantly with the pulmonary (r=-.33, p<.03) and gynecological (r=-.39, p<.03) domains (Figure 2).
Table 1. Initial assessment – significant correlations of hormones with MQ symptom domains *Note all symptoms include genitourinary, musculoskeletal, immunological, pulmonary, and gynecological
| Hormone | Symptom Domain | r | P | Hormone Change |
| DHEA | Genitourinary | 0.30 | <0.05 | Increase |
| Estrone | Musculoskeletal | -0.43 | <0.012 | Decrease |
| FSH | Pulmonary | -0.29 | <0.05 | Decrease |