Sexual Functioning and Opioid Maintenance Treatment in Women. Results From a Large Multicentre Study

Abstract

Opioid maintenance treatment (OMT) is the most widespread therapy for both females and males opioid addicts. While many studies have evaluated the OMT impact on men’s sexuality, the data collected about the change in women’s sexual functioning is still limited despite the fact that it is now well-known that opioids - both endogenous and exogenous - affect the endocrine system and play an important role in sexual functioning. The present study aims to determine how OMT with buprenorphine (BUP) or methadone (MTD) affects sexual health in women; examining also any possible emerging correlation between sexual dysfunction (SD), type of opioid and patients’ mental health. This multi-center study case recruited 258 female volunteers attending Italian public Addiction Outpatients Centers that were stabilized with OMT for at least 3 months. SD was assessed with the Arizona Sexual Experience Scale. The twelve-item General Health Questionnaire was used to assess participants’ mental health conditions. The results show that 56.6% of women receiving OMT for at least 3 months presented SD without significant differences between MTD e BUP groups. The majority of the subjects with SD have a poorer quality of intimate relationships and worse mental health than the average. To the best of our knowledge, the present study is the largest report on the presence of SDs in women as a side effects of MTD and BUP used in OMT. Since SDs cause difficulties in intimate relationships, lower patients’ quality of life and interfere with OMT beneficial outcomes, we recommend that women undertaking an opioid therapy have routine screening for SD and we highlight the importance to better examine opioid-endocrine interactions in future studies in order to provide alternative potential treatments such as the choice of opioid, opioid dose reduction and hormone supplementation.

Full text

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ORIGINAL RESEARCH
published: 14 May 2019
doi: 10.3389/fnbeh.2019.00097
Edited by:
Patrizia Porcu,
Institute of Neuroscience (CNR), Italy
Reviewed by:
Christina Dalla,
National and Kapodistrian University
of Athens, Greece
Jana Ruda-Kucerova,
Masaryk University, Czechia
*Correspondence:
Lorenzo Zamboni
lorenzo.zamboni88@gmail.com
Received: 18 February 2019
Accepted: 23 April 2019
Published: 14 May 2019
Citation:
Zamboni L, Franceschini A,
Portoghese I, Morbioli L, Lugoboni F
and GICS Group (2019) Sexual
Functioning and Opioid Maintenance
Treatment in Women. Results From
a Large Multicentre Study.
Front. Behav. Neurosci. 13:97.
doi: 10.3389/fnbeh.2019.00097
Sexual Functioning and Opioid
Maintenance Treatment in Women.
Results From a Large
Multicentre Study
Lorenzo Zamboni1*, Anna Franceschini2, Igor Portoghese3, Laura Morbioli1,
Fabio Lugoboni1and GICS Group4
1Department of Medicine, Verona University Hospital, Verona, Italy, 2Addictive Behaviors Department, Local Health
Authority, Treviso, Italy, 3Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy, 4Gruppo
InterSerT di Collaborazione Scientifica (GICS), Verona, Italy
Opioid maintenance treatment (OMT) is the most widespread therapy for both females
and males opioid addicts. While many studies have evaluated the OMT impact on
men’s sexuality, the data collected about the change in women’s sexual functioning is
still limited despite the fact that it is now well-known that opioids - both endogenous
and exogenous - affect the endocrine system and play an important role in sexual
functioning. The present study aims to determine how OMT with buprenorphine (BUP) or
methadone (MTD) affects sexual health in women; examining also any possible emerging
correlation between sexual dysfunction (SD), type of opioid and patients’ mental health.
This multi-center study case recruited 258 female volunteers attending Italian public
Addiction Outpatients Centers that were stabilized with OMT for at least 3 months.
SD was assessed with the Arizona Sexual Experience Scale. The twelve-item General
Health Questionnaire was used to assess participants’ mental health conditions. The
results show that 56.6% of women receiving OMT for at least 3 months presented
SD without significant differences between MTD e BUP groups. The majority of the
subjects with SD have a poorer quality of intimate relationships and worse mental
health than the average. To the best of our knowledge, the present study is the largest
report on the presence of SDs in women as a side effects of MTD and BUP used in
OMT. Since SDs cause difficulties in intimate relationships, lower patients’ quality of life
and interfere with OMT beneficial outcomes, we recommend that women undertaking
an opioid therapy have routine screening for SD and we highlight the importance
to better examine opioid-endocrine interactions in future studies in order to provide
alternative potential treatments such as the choice of opioid, opioid dose reduction and
hormone supplementation.
Keywords: methadone, addiction, quality of life, women sexuality, buprenorphine
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Zamboni et al. Women’s Sexuality and Opioid Maintenance Treatment
INTRODUCTION
The World Health Organization (WHO) describes sexual health
as a state of physical, emotional, mental and social well-being
in relation to sexuality itself and recognizes it as a right
to every human being (World Health Organization [WHO],
2006). It is commonly accepted that a healthy sexuality is
fundamental to one’s sense of self-worth (Kaplan, 1974); it
represents the integration of the biological, emotional, social, and
spiritual aspects of who one is and how one relates to others
(Covington, 1997).
Despite its proven capital importance for human self-esteem,
sexuality has been a neglected topic in scientific research and in
treatment of women with Substance Use Disorders (SUD) to this
day. Reproduction intended as a combination of contraception,
pregnancy, parenthood and risky sexual behavior (i.e., sexually
transmitted diseases and prostitution), is the aspect drawing most
of the attention in terms of research and special health services
for women. Although these aspects deserve priority in regards to
feminine sexuality, they are not fully exhaustive on the matter.
The lack of professional study cases on the relationship
between SUD and sexual functioning appears more evident
considering sexual health in opioid dependent women under
Opioid Maintenance Treatment (OMT) on buprenorphine
(BUP) and methadone (MTD). To this day we have a serious
lack of data in regards to this topic despite the fact that opioids
-both endogenous and exogenous- evidently affect the endocrine
system (Katz and Mazer, 2009;Rhodin et al., 2010;Voung
et al., 2010) and play an important role in sexual functioning
(Palha and Esteves, 2008).
Sexual dysfunctions (SDs) are a frequent adverse effect during
opioid treatment for both men and women however, most
of the studies had been conducted basing the researches on
male candidates receiving OMT (Brown and Zueldorff, 2007;
Lugoboni et al., 2017).
To date most of the studies that have analyzed the
impact of opioid treatment on female sexuality had been
conducted on women treated with opioid analgesics aimed to
cure non-malignant chronic pain. These studies demonstrated
that opioids inhibit the production of multiple hypothalamic,
pituitary, ovarian and adrenal hormones, causing opioid-
induced hypogonadotropic hypogonadism that can determine
amenorrhea or hypomenorrhea, SDs, fatigue and depression in
female patients (Daniell, 2008;Rhodin et al., 2010).
Opioid maintenance treatment combined with psychosocial
interventions is the most widespread treatment for opioid
dependence. In Europe MTD is currently the most prescribed
medicine against heroine dependency: 69% of opioid dependent
patients are undergoing this treatment, meanwhile the 28% of the
subjects is assuming BUP. Among 700.000 European patients in
OMT, 20% is represented by women (EMCDDA, 2015).
Given the fact that one of the main goals of the OMT is the
amelioration of the patients’ quality of life and their reintegration
in a gratifying social life, it is clear how assessing and curing
eventual SDs in both female and male OMT patients is of primary
importance. It is also demonstrated that iatrogenic sexual
disorders can act against treatment retention and achievement of
a good quality of life for the patients (Xia et al., 2013).
Taking into account the limited number of monitored and
rigorous studies regarding OMT and SDs as a side effect of
this therapy in women, the present study puts its focus on the
presence of SDs in Italian female patients treated for opioid
dependence with MTD or BUP in specialized outpatient centers.
The authors hypothesize that OMT impacts the sexual health of
opioid addicted women, as it is already ascertained in men, and
they aim to examine if there is any correlation between possible
SD, type of opioid, daily dose administration and patients’ mental
health. Due to the factors explained above, the results of this
study could help to find evidence-based models that would allow
assisting clinicians to address and treat sexual issues and related
concerns with aimed therapy.
MATERIALS AND METHODS
The study was conducted in 20 Addiction Treatment for
Outpatients Centers of the Italian public health system. The
philosophy of intervention, policies and procedures applied were
similar in each Center and the accessibility threshold was the
same across all structures.
Italian Addiction Treatment Services provide outpatient
treatment programs with a variety of therapeutic and
rehabilitative strategies: MTD, BUP, and naltrexone are
administered in association with possible psychosocial
interventions, such as psychotherapy, family therapy,
group therapy, social support and medications for
psychiatric co-morbidity.
The selected centers did not differ in the psychosocial
treatment protocols associated with MTD and BUP, or in the
admission criteria. In the Italian Addiction Services the majority
of patients are heroin addicts. There are no exclusion criteria
regarding the access to the public health system. Patients who fail
to respond to interventions such as OMT and continue to inject
heroin are not dismissed by these centers.
Between 1st July and 31st December, 2015, a cross-sectional
survey was administered to a large sample of patients receiving
MTD or BUP maintenance treatment for heroin dependence.
The sample included 258 women between the age of 18 and
61 (mean age: 37) enrolled in a drug recovery program in
treatment centers for clinically diagnosed heroin dependence
(American Psychiatric Association, 2000) DSM IV TR. Patients
were receiving either MTD (N 198, 76.7%; mean daily dose
60.5 mg) or BUP (N 56, 23.3%; mean daily dose 10.8 mg)
maintenance in combination with psychosocial treatment. At the
time of the study they had been stabilized with an OMT for
at least 3 months.
Underage patients, subjects following a drug-free treatment or
an opioid substitution therapy for less than 3 months (and/or
other than MTD/BUP) were excluded from the study case and
also those who presented difficulty of language comprehension.
The questionnaires and data sheets were delivered by a nurse
to the participating patients. This was done to optimize patients’
privacy and to minimally affect responses, as nurses are less
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involved in therapy compared to doctors and psychologists.
Patients filled the questionnaires at the facility or at home
and handed the documents anonymously. As indicated by a
previous focus group among surveyed patients the collection of
the questionnaires was carried out using an urn and not by direct
delivery to the staff. Patients gave a written informed consent
in order to take part to this survey, which was approved by the
Public Health System ethical committee of Verona University
Hospital in Verona, Italy. All participants were volunteers and
were not paid for their participation. The patients could stop
the survey’s compilation at any time. Study procedures did not
interfere with the daily protocols of the centers.
Measures
Sexual dysfunction was assessed by the Arizona Sexual
Experience Scale (ASEX) (McGahuey et al., 2000). It is composed
by five items rated on a 6-point Likert-type scale, with higher
scores reflecting greater or lower dysfunction level. Each item
quantifies a major domain of sexual function, sexual drive,
psychological arousal, physiologic arousal (vaginal lubrication
for women), ability to reach orgasm, and orgasm satisfaction
(e.g., “How easily are you sexually aroused?”). Cases of SD were
established according to three criteria: (a) a total score ≥19; (b)
any item with an individual score ≥5; and (c) any three or more
items scoring ≥4 were considered as SD (McGahuey et al., 2000).
These three criteria showed optimal sensitivity and specificity
for SD. The main dependent variable for all the analyses will
use cases applying all those criteria (0, “not SD,” 1 “SD”), and
analyses will be repeated for each specific criterion in order to
test possible differences with more restrictive definitions. In the
present study, the internal reliability was 0.86.
The twelve-item General Health Questionnaire (GHQ-12)
was used to assess the mental state of the participants.
This tool is intended to screen for general (non-psychotic)
psychiatric morbidity (Goldberg and Williams, 1988; e.g., “Have
you recently felt you couldn’t overcome your difficulties?”).
It has been widely used and translated into many languages
and extensively validated in general and clinical populations
worldwide (Werneke et al., 2000). Items were answered on a
4-point scale from 0 (not at all) to 3 (much more than usual).
Higher scores indicate poorer mental health. In the present
study, the internal reliability was 0.89.
The questionnaire also included demographic and drug
related variables such as age, marital status, education level, and
use and dosage of MTD and BUP. The respondents completed
anonymously all questionnaires.
Statistical Analysis
At first, differences in proportions or means between
patients with or without SD were compared with chi-
square tests (categorical variables) and t-tests for unrelated
samples (continuous).
In order to assess the strength of the associations with
categorical variables the Cramer’s V coefficient of association
(range from 0 for no association to 1 as perfect association) was
calculated, whereas the effect size (Hedge’s g) was measured on
associations with continuous variables.
Hedge’s g provides values that are very similar to Cohen’s d
[d = g/sqrt (N/df)] for which the following arbitrary rules of
thumb are often used: 0.2–0.3, small effect; 0.5, moderate effect;
and 0.8, large effect (Cohen, 1988).
A confirmatory factor analyses (CFA) was carried out for
examining the distinctiveness of the scales used in this study.
More specifically, we compared a full measurement model to a
one-factor structure (where items were set to load into a common
factor). The model ft was tested considering the Comparative Fit
Index (CFI), the Incremental Fit Index (IFI), and the Root-Mean-
Square Error of Approximation (RMSEA). According to Kline
(2005) and Byrne (2016), the CFI and IFI values should have a
cutoff value of ≥0.90, and RMSEA a value of ≤0.08 to indicate
a good ft of the model. Reliability analysis was performed using
Cronbach’s αmeasure.
Finally, to examine whether demographics (age, marital
status, and education level), use of MTD and BUP, and overall
psychological well-being were predictive of sex dysfunction, a
stepwise multiple regression analysis was carried out. A P-value
<0.05 was considered statistically significant.
Statistical analyses were carried out using PASW Statistics 18·0
and AMOS 16·0 (Chicago, IL, United States, Arbuckle, 2007).
RESULTS
Factorial Validity of the Scales
Results from CFA showed that the hypothesized two-factor
model (χ2 = 297.25 df = 113, P<0.01, RMSEA = 0.079,
CFI = 0.92, IFI = 0.92) fits the data significantly better than the
one general factor model (χ2 = 606.26, df = 114, P<0.01,
RMSEA = 0.130, CFI = 0.78, IFI = 0.78) providing evidence of
discriminable different factors.
Descriptive Statistics
A total of 56.6% (SE = 3.1; n= 146) of the sampled patients
manifested SD considering the three criteria explained above.
18.6% (SE = 2.4; n= 48) fulfilled criterion a, 43.0% criterion
b (SE = 3.1; n= 111), and 43.4% criterion c (SE = 3.1;
n= 112). In the total sample the mean age was 37.7 years
(SD = 10.6; range: 18–61); 61.3% of the subjects were single,
15.2% married, 18.4% divorced or separated and 5.1% widowed;
69.0% presented a secondary education level while the 26.4% had
a higher education, and 4.7% an elementary level of education.
76.4% (n= 197) were taking MTD with an average of 60.6 mg
(SD = 73.5) and 20.6% (n= 53) were taking BUP with an average
of 10.5 mg (SD = 7.6). The mean score in the GHQ for the total
sample was 14.6 (SD = 7.0).
Comparisons between those with and without SDs indicated
that women with SDs were older, were more often separated or
divorced, had lower levels of education, assumed higher doses of
MTD (among those consuming the drug), and presented a poorer
mental health as measured by the GHQ12. No differences among
groups were found in regards to the percentage of patients taking
MTD or BUP or the doses of this last drug. All these results are
summarized in Tables 1,2.
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TABLE 1 | Characteristics of the sample according to the presence of
sexual dysfunction.
Variables Sexual
dysfunction
N= 146
Not sexual
dysfunction
N= 112
p g (95% CI) or
V
Age 39.1 (11.1) 35.5 (9.9) 0.006 0.34
(0.09,0.59)
Marital status
(%)
Married 13.2 (2.8)∗17.9 (3.6)∗0.048 0.176
Widowed 6.9 (2.1)∗2.7 (1.5)∗
Divorced/
separated
22.9 (3.5)∗12.5 (3.1)∗
Single 56.9 (4.1)∗67.0 (4.5)∗
Education level
(%)
0.004 0.209
Elementary 6.9 (2.1)∗1.8 (1.3)∗
Secondary 74.0 (3.6)∗62.5 (4.6)∗
Higher 19.2 (3.3)∗35.7 (4.5)∗
Methadone (%
yes)
80.1 (3.3)∗71.4 (4.3)∗0.103 0.102
Methadone, mg 69.4 (91.1) 47.6 (30.3) 0.041 0.30
(0.01,0.58)
Buprenorphine
(% yes)
17.2 (3.1)∗25.0 (4.1)∗0.127 0.095
Buprenorphine,
mg
8.9 (8.2)∗12.0 (6.7)∗0.132 0.41
(−0.13,0.95)
GHQ 16.0 (7.1) 12.8 (6.4) <0.001 0.47
(0.22,0.42)
Values between brackets are standard deviations unless indicated: ∗, Standard
errors. Comparisons: t-tests for continuous variables, chi-square tests for
categorical variables g, Hedge’s effect size, V, Cramer’s V. Values in bold are
statistically significant (p <0.05).
TABLE 2 | Results of logistic regression analyses, persons without sexual
dysfunction (reference category) vs. persons with sexual dysfunction, unadjusted
and controlling for age (except for the age effect).
Variables OR, unadjusted
(95% CI)
OR, adjusted
(95% CI)
Age 1.03 (1.01,1.06)
Marital status (ref.: single)
Married 0.87 (0.43,1.75) 0.73 (0.35,1.51)
Widowed 3.05 (0.81,11.50) 2.15 (0.54,8.53)
Divorced/separated 2.16 (1.07,4.34) 1.56 (0.72,3.36)
Education level (ref.:
elementary)
Secondary 0.31 (0.07,1.45) 0.33 (0.07,1.58)
Higher 0.14 (0.03,0.69) 0.16 (0.03, 0.80)
Methadone (ref.: No) 1.61 (0.91,2.87) 1.70 (0.95,3.07)
Methadone, mg 1.01 (1.001,1.02) 1.01 (1.0001,1.02)
Buprenorphine (ref.: No) 0.62 (0.34,1.15) 0.58 (0.31,1.07)
Buprenorphine, mg 0.94 (0.87,1.02) 0.94 (0.87,1.02)
GHQ 1.07 (1.03,1.12) 1.09 (1.04,1.13)
Numbers in bold indicate statistically significant effects (p <0.05).
Interestingly, when performing the same analyses using more
restrictive definitions of SD, results did not change for criteria b
(any one item with a score ≥5) and c (any three or more items
with scores ≥4), while in regards to criteria a (cut-off score in the
total scale ≥19) there was no difference shown in the severity of
mental health symptoms.
As shown in Table 3, only one significant effect emerged
for item # 2 (easiness for sexual activation) when analyzing
distribution of scores for specific ASEX items in women taking
or not taking MTD. Subjects taking MTD reported higher
difficulty for getting aroused, with an average effect size (Cramer’s
V= 0.286). The total ASEX score, however, did not significantly
differ [t(256) = 0.15; p= 0.882] between those taking MTD
(mean = 14.77, SD = 4.58) or BUP (mean = 14.67, SD = 4.51).
Hierarchical Regression Analyses
Stepwise multiple regression analysis was conducted with
individual characteristics as shown in Table 4, including age,
marital status, and education level, use of MTD and BUP, and
overall psychological well-being as predictor variables and sex
dysfunction as criterion (dependent) variables. Table 4 shows that
the model accounted for 6.5% of the criterion variance.
Overall psychological well-being was the only significant
predictor (β= 0.27, p<0.001).
DISCUSSION
The scientific literature that treats gender differences in SUD is
rather recent and it highlights substantial differences between
men and women. It is demonstrated by these studies that gender
influences the prevalence, the origin, the progression and the
outcome of these disorders. Women showed a quicker transition
from use to dependence (Becker and Hu, 2008), worse clinical
conditions at the time of admission, more frequent comorbidity
for depression and anxiety, increased suicide risk, and worse
physical health compared to men presenting opioid use disorder.
Psychiatric comorbidity often precedes and favor onset of SUD
in women, such as post-traumatic stress disorder which is found
related to physical and sexual abuse in all ages and worst
socioeconomic conditions (Cotto et al., 2010;Eiroá-Orosa et al.,
2010;Back et al., 2011). Women indulge in sexual risky behavior
more than men by avoiding condom use, choosing a greater
number of sexual partners and using sex in exchange of money
and/or drugs more frequently; women also tend to choose stable
partners with SUD (Quaglio et al., 2004, 2006). They often
accept unprotected sex in order to grant the continuity of the
relationship (Sheeran et al., 1999). Numerous studies verified that
intimate partner violence and childhood sexual abuse in general
population are strongly related to risky sexual behaviors and to
the occurrence of sexually transmitted diseases (Urada et al.,
2013). These dynamics facilitate the manifestation of unbalanced
love or sexual relationships that favor the masculine partner’s
power. Together with SUD these situations jeopardize women’s
determination to look for and find a healthy sexual life (Engstrom
et al., 2012;Gilbert et al., 2015).
To this day gender studies have largely neglected the sexual
aspects of opioid dependent women and to the best of our
knowledge, the present study is the largest report on women
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TABLE 3 | Association between responses to specific items from the ASEX and the use of MTD (% of persons using MTD responding to each category).
Items 1 2 3 4 5 6 p V
How strong is your sex drive? 1.52 12.69 22.34 31.47 21.83 10.15 0.210 0.167
How easily are you sexually aroused (turned on)? 1.53 10.71 20.92 39.80 21.94 5.10 0.001 0.286
How easily does your vagina becomes moist or wet during sex? 6.12 22.45 25.51 28.57 12.76 4.59 0.265 0.159
How easily can you reach an orgasm? 1.80 15.32 27.03 33.33 16.22 6.31 0.146 0.146
Are your orgasms satisfying? 9.91 31.53 29.73 16.22 7.21 5.41 0.071 0.259
From 1 “extremely strong/ easily/ satisfying” to 6 “no sex drive/ never/ can’t reach orgasm.” Higher scores means more sexual dysfunction. Numbers in bold indicate
statistically significant effects (p <0.05); tests: chi-square (df = 5).
with SD on MTD or BUP maintenance treatment. It focuses on
the sexual health of 258 women in OMT using consistent and
validated measures of SD and also evaluating other factors (i.e.,
demographic data, mental health, and opioid dose), that could
contribute to SD. The results show that 56.6% of women receiving
BUP or MTD for at least 3 months show SD without significant
differences between MTD e BUP groups.
These results differ from the ones reported by Moreira et al.
(2008), in a large community survey that showed how 30.1% of
adult women in Southern Europe (Italy, Spain, France) suffer
from lack of sexual interest, while 22.7% experience lack of
sexual pleasure and 24.8% incur inability to reach orgasm. These
percentages indicate that female patients in OMT have a higher
rate of SDs in comparison to the general population.
In the present study the MTD group shows a significantly
higher excitation disturbance compared to the BUP group while
considering specific ASEX issues. These results are consistent
with those of the study conducted by Giacomuzzi et al.
(2009), which demonstrated how, in a small sample of 30
women in OMT, it is harder to reach orgasms while taking
MTD instead of BUP.
Furthermore, demographic variables emerged from this study,
BUP and\or MTD intake are not significant predictors of SDs,
and the majority of subjects with SD have a quality of intimate
relationship and mental health poorer than the average. The
results from the stepwise regression show how women’s overall
psychological well-being is positively linked to SD. These findings
are consistent with those of other studies reporting SD, anxiety
and depression in women treated with opioid in chronic pain
(Daniell, 2008;Katz and Mazer, 2009). The relationship between
mood disorders and SD is actually still unsettled in women in
TABLE 4 | Stepwise linear regression analysis of predictors of sexual dysfunction
(N= 258).
Variables B SE ß P-value
Age 0,008 0,03 0,019 0,784
Marital status 0,33 0,271 0,085 0,224
Education level 0,109 0,3 0,023 0,716
MET −1,566 1,605 −0,147 0,33
BUP −1,743 1,684 −0,155 0,302
Overall psychological well-being 0,176 0,041 0,271 0,000
Predictors of sexual dysfunction final model produced at p = 0.05, F = 3,85,
P<0.01, R2= 0.063.
OMT, but in many cases it could be directly associated with
opioid-induced hypogonadotropic hypogonadism, especially for
impaired androgen production. The testosterone opioid-induced
suppression can have important consequences other than SD,
such as potential anxiety, depression, fatigue and a generally
reduced quality of life. These symptoms were reported to have
improved with androgen supplementation in women undergoing
long-term opioid treatment (Brown and Zueldorff, 2007;Katz
and Mazer, 2009). As a matter of fact, the presence of depression,
anxiety and a generally reduced quality of life are common
in women in OMT and could be due to associated conditions
and co-morbidities (i.e., other medications, primary psychiatric
disorders, other medical conditions, use of other substances low
socioeconomic status), regardless of the opioid treatment. In
case of co-presence of these symptoms and SDs, female patients
in OMT should be assessed for opioid-induced hypogonadism
by laboratory endocrine evaluation to investigate if alterated
gonadal hormon levels play any role in SDs and in mood and/or
anxiety disorders.
Furthermore, demographic variables taking BUP and\or MTD
were not significant predictors of SD.
It is important to mention the correlation between MTD dose
and SD emerged by this study, dynamic which is not present in
BUP groups. Other studies have shown a dose-response effect in
patients undergoing MTD treatment due to boosting testosterone
suppression by increasing the dose of MTD. This result is clearer
in men than in women, due to limited scientific information on
testosterone levels in female patient undergoing MTD treatment
(Bawor et al., 2014). Our outcomes are in line with the previous
study carried out by Parvaresh et al. (2015) that used ASEX
and focused on MTD dose-related effect in sexual functioning in
adult women. Conversely there is no evidence in literature of a
link between SD and BUP dosage in women in OMT treatment
or about testosterone level in these subjects. If further studies
on women will confirm the correlation between SDs and MTD
dosages and on the contrary no correlation with BUP dose, this
issue should be taken into account at the moment of choice
of opioid medication, especially because there are findings that
women need higher MTD doses compared to man in order to
avoid quitting the treatment (Vigna-Taglianti et al., 2016). The
reason behind this last result is still unclear, hypothetically it
could be partially associated to the evidence that higher MTD
dosages are requested in patients diagnosed with post traumatic
stress disorder or depression (Trafton et al., 2006). These illnesses
are more frequent in women than in men as explained above.
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Moreover it should be noted that, despite the lack of evidence
in literature of the correlation between the severity of SUD and
MTD or BUP dosages needed in OMT, higher MTD doses are
predictive of major reduction in illicit opioid consuming in both
men and women (Fareed et al., 2009).
CONCLUSION
Sexual dysfunctions may cause difficulties in intimate
relationships, lower patients’ quality of life, can favor and
maintain the SUD, interfere with OMT beneficial outcomes
and influence adherence to treatment (Brown and Zueldorff,
2007;Xia et al., 2013;Bawor et al., 2014). It is important to
explore the cause of SDs through a multidimensional evaluation.
It is very important to inform patients on the possible side
effects of opioid therapy on their sexuality and when present,
to their treatment also. Spreading the information can avoid the
arousal of negative thoughts about themselves and their sexual
self-efficacy.
This study shows how OMT can determine sexual side
effects in women despite being an essential and effective
treatment in opioid addicted patients. Unfortunately, the lack
of evidence about SD in women in OMT implicates absence
of intervention models in case of sexual disturbances. This can
be an obstacle to clinicians to carefully enquire about sexual
health in these subjects. Women on opioid therapy should have
routine screening for SD longitudinally, and should be treated
with appropriate measures.
In the light of the above-mentioned considerations, we now
understand the necessity of continuing the studies in order to
overcome the existing limited literature about opioid induced SD
in women and therefore better examine hypogonadism in women
in OMT. The aim is to provide female patients the chance to
eventually apply potential treatments like the choice of opioid,
opioid dose reduction and androgen supplementation.
GICS MEMBERS
There are GICS’s members, the group had help us to find the
patients for this study: Arzillo C., Benigna L., Bersani N., Bersani
P., Betti O., Biasin C., Bossi C., Bottazzo A., Bove A., Caccamo E.,
Cancian S., Cantanchin F., Cantiero D., Canzian G., Cargnelutti
D., Casalboni D., Casari R., Casarini R., Cibin M., Civitelli P.,
Cozzi T., De Cecco L., Del Zotto R., Dellantonio E., Dersini F.,
Duranti I., Faccini M., Fadelli M., Favero E., Fona B., Fontana
N., Franceschini A., Gaiga E., Gardiolo M., Gentile N., Gervino
D., Ghezzo N., Giacomin MA., Kashanpour H., Lietta P., Manera
E., Manzato E., Mazzo M., Meneghello D., Mihalcea C., Milan
E., Montresor M., Moratti E., Musso D., Musso M., Pani A.,
Pavani V., Peroni F., Pellachin P., Piazza M., Prosa D., Pupulin
B., Rescigno B., Resentera C., M. Residori., Ricci C., Righetti P.,
Ripoli MA., Riscica P., Rizza C., Rizzetto V., Rossi A., Rovea
A., Ruffato A., Ruzziconi C., Sabbion R., Santo E., Scarzella M.,
Sembianti N., Simonetto P., Smacchia C., Stellato M., Stimolo C.,
Suardi L., Vaiana A., Zavan V., Zerbetto E., Zerman M.
Limitations of the Study
Whereas the strength of the present study is its larger sample
size compared to previous researches, the limitations concern
the questionnaire as it is self-reported and the definition of SD
as it is subjective. A lack of sexual activity, for example, is not
always perceived as SD; personal views (i.e., cultural, religious, or
other) often bias interpretation. Furthermore this research lacks
a longitudinal perspective. As this research was cross-sectional,
we were unable to analyze causal influence and changes in the
studied variables across time.
DATA AVAILABILITY
All datasets generated for this study are included in the
manuscript and/or the supplementary files.
AUTHOR CONTRIBUTIONS
FL was responsible for the study concept and design. GICS
contributed to the data acquisition. LZ assisted with the data
analysis and interpretation of findings. AF and LM drafted
the manuscript. All authors critically reviewed the content and
approved the final version of the manuscript for publication.
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Conflict of Interest Statement: The authors declare that the research was
conducted in the absence of any commercial or financial relationships that could
be construed as a potential conflict of interest.
Copyright © 2019 Zamboni, Franceschini, Portoghese, Morbioli, Lugoboni and GICS
Group. This is an open-access article distributed under the terms of the Creative
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