The fluctuation of estradiol and progesterone levels across the menstrual cycle influences the endogenous opioid system, but it is unknown if this change in hormone levels affects the response to naltrexone. Additionally, hormonal contraception is known to affect cortisol response to stress, but it is unclear if its use would also impact hormonal response to naltrexone. With this in mind, the studies in this dissertation were designed to investigate whether endogenous (differences in sex hormone levels due to menstrual cycle phase) and exogenous factors (hormonal contraception) contribute to sex differences in response to naltrexone.
The first study of this dissertation demonstrated that women had a greater ACTH and cortisol response to naltrexone than men, corroborating several studies indicating sex differences in response to opioid receptor agonists and antagonists. In order to identify a mechanism contributing to this result, I designed a follow-up study to investigate the effects of menstrual cycle phase on hormonal and subjective response to naltrexone. In contrast to the results of the first study, the results of the follow-up study indicated that sex differences in response to naltrexone may only be apparent when testing women at certain times of the menstrual cycle. Women in the luteal phase of the menstrual cycle had significantly greater hormonal and subjective response to naltrexone than both women tested during the early follicular phase and men, while the latter two groups generally did not differ in their response. These results suggest that men and women do not have static, organizational differences in the endogenous opioid system, but instead, endogenous opioid activity fluctuates across the menstrual cycle, creating phase-specific sex differences.
The third study presented in this dissertation indicated that hormonal contraception can also influence response to naltrexone. Women using hormonal contraception demonstrated a significantly attenuated salivary cortisol diurnal rhythm, as well as blunted cortisol response to a stressor and naltrexone, than non-contraception using women. However, in contrast to the menstrual cycle-related results, subjective response to naltrexone and a stressor did not differ between groups. Because naltrexone's effects on subjective mood are related to its effects on opioid transmission, these results suggest hormonal contraception can affect responses to naltrexone without altering the endogenous opioid system.
The results presented in this dissertation have at least two major implications. Naltrexone, along with nalmefene and naloxone, is commonly used in laboratory studies to probe endogenous neurotransmitter (e.g., opioids and dopamine) and hormone systems. Thus, one implication from the current results is that menstrual cycle phase and hormonal contraception use should be taken into account when designing studies measuring hormonal and subjective response to naltrexone in women. More importantly, these results could also impact the use of naltrexone in the treatment of addictions. For example, the date to start naltrexone treatment could be planned to coincide with a menstrual cycle phase that that coincides with a drug-sensitivity that is optimal for medication efficacy. Future studies should replicate the current results in drug-dependent populations that are candidates to receive naltrexone pharmacotherapy. If women in these patient populations are still shown to have increased sensitivity to naltrexone during the luteal phase of the menstrual cycle, then follow-up studies should examine the relationship between starting treatment at various points of the menstrual cycle and treatment outcomes. (Abstract shortened by UMI.)
|Advisor:||King, Andrea C., Mason, Peggy|
|Commitee:||Kim, Helen, McGehee, Daniel, Prendergast, Brian|
|School:||The University of Chicago|
|School Location:||United States -- Illinois|
|Source:||DAI-B 74/05(E), Dissertation Abstracts International|
|Subjects:||Neurosciences, Endocrinology, Pharmacology|
|Keywords:||Hormonal contraception, Hypothalamic pituitary adrenal axis, Hypothalamic pituitary gonadal axis, Menstrual cycle, Naltrexone, Prolactin|
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