Agradecendo a colegas da área de saúde da UFPE pela indicação, reproduzo aí abaixo paper de Helen Conaglen e John Canaglen sobre a relação entre a temática das drogas (aí incluídos os fármacos) e a questão da sexualidade. Como variável interveniente, em nossas pesquisas sobre as drogas, tem sido possível - seja do ponto de vista empírico, seja no tocante às ilações da literatura especializada - verificar um desvio padrão consistente, a depender da amostragem, no que se refere à correlação estatística entre drogas e sexo. Daí emergem também as inferências, convalidadas em estudos realizados em outros países, a respeito do 'desperdício da sexualidade', da 'sexualidade instantânea', da 'sexualidade dissociada de prazer físico-emocional', etc. São fenômenos que envolvem tanto o sexo masculino como o feminino. As razões para tanto são diversas. A seguir, a reprodução do paper.
Helen M Conaglen
Clinical psychologist and Senior research fellow, University of Auckland
John V Conaglen
Faculty of Medical and Health Sciences, University of Auckland
(Publicado in: Australian Prescriber, v. 36, nº 02, 2013)
Introduction
Several classes of
prescription drugs contribute to sexual dysfunction in men and women (Table 1).1-3 Patients
who develop drug-induced sexual dysfunction are more likely to be non-adherent.
This has been found with antihypertensives4 and
antipsychotics5 .
The literature has emphasised male sexual problems with less data available on
female or couple problems.
Recreational drugs such as
alcohol, narcotics, stimulants and hallucinogens also affect sexual function.
Short-term use of alcohol affects sexual desire by decreasing inhibitions, but
also diminishes performance and delays orgasm and ejaculation. Many substance
abusers report better sexual function, but often their partners report the
opposite.6
Sexual function consists of
the phases of sexual desire, arousal and orgasm. Both men and women can
experience problems in any of these phases. Low desire, lack of swelling and
lubrication in women, erectile dysfunction, premature, retrograde or absent
ejaculation, anorgasmia and painful sex not only affect the individual, but
also impact on their partner.
Talking
to the patient
Whether patients report
their sexual problems depends on several factors, including whether the patient
is comfortable disclosing these problems, and whether the clinician is willing
to ask about sexual issues and does so in a sensitive way.7 ,8Patients
on long-term medications may not be aware that their sexual problems have
developed as a result of their treatment. Conversely some may blame their drugs
for sexual problems which are due to relationship difficulties or other
stressors. Some doctors consider that asking patients if they had noticed any
sexual adverse effects from their drugs may 'suggest' them to the patient, and
possibly result in non-adherence. Patients attributing their sexual problems to
their drugs are less likely to continue the treatment even when necessary for
their health.9 The
consultation should include discussion of the patient's sexual issues so these
can be considered in treatment decisions.
Treatments
for hypertension
Hypertension is associated
with sexual dysfunction.10 Antihypertensives
may also contribute to the problem and lead to low treatment adherence.4
Men
In an international survey,
20% of men using beta blockers (beta adrenoreceptor antagonists) for
hypertension had erectile dysfunction.11 Centrally-acting
alpha agonists (for example clonidine) and diuretics have also been implicated
in impairing sexual function.4 The
aldosterone receptor blocker spironolactone also blocks the androgen receptor
and is associated with erectile dysfunction and gynaecomastia.
Women
Sexual dysfunction is more
common in women with hypertension (before treatment) compared to normotensive
women (42% vs 19%).12 Although
the sexual effects of antihypertensives have been poorly studied in women,
these drugs may have similar adverse effects on the arousal phase as in men,
leading to failure of swelling and lubrication. Decreased sexual desire (41% of
women) and sexual pleasure (34%) have been reported.13 Alpha
adrenergic drugs such as clonidine and prazosin also reduce desire (in a small,
randomised trial)14 and
arousal15 .
The angiotensin II receptor antagonist, valsartan, was associated with improved
sexual desire and fantasies when compared with the beta blocker atenolol in
women with hypertension.16
Psychoactive
drugs
Aside from the medicine, it
is important to be aware of the effects of psychiatric problems on the
patient's relationship and address the psychosocial issues.17 Up
to 70% of patients with depression have sexual dysfunction, which can affect
any phase of sexual activity.18 Reports
indicate that 30–80% of women and 45–80% of men with schizophrenia also
experience sexual problems.19 In
these patients, it may be difficult to distinguish the effects of the illness
on sexual function from the effects of the drugs used for treatment.
Antidepressants
Many antidepressants cause
sexual difficulties.17 ,20 Selective
serotonin reuptake inhibitors and serotonin noradrenaline reuptake inhibitors
inhibit desire, cause erectile dysfunction and decrease vaginal lubrication.
They also impair orgasm in 5–71% of patients.18 ,21 ,22 This
adverse effect is used therapeutically to delay premature ejaculation.
Tricyclic antidepressants
inhibit sexual desire and orgasm.23,24 The
effects of specific drugs vary depending on their mechanism of action. For
example, clomipramine causes orgasmic difficulties in up to 90% of patients,
while nortriptyline causes more erectile dysfunction but has less effect on
orgasm.25
Monoamine oxidase
inhibitors are also associated with sexual dysfunction. Although moclobemide
was reported to increase sexual desire,24 the
doses used in that study were considered subtherapeutic.
Other antidepressants such as
venlafaxine and mirtazapine have variable negative effects on all aspects of
sexual function. Initial reports on agomelatine in both male and female
patients with major depressive disorder suggested significant antidepressant
efficacy without significant sexual adverse effects. However, more recent
reviews of the sexual effects are conflicting.26 ,27
Antipsychotics
Some antipsychotics may
affect sexual function more than others (see Table 2).19 ,28 The
only Cochrane review of antipsychotic-induced sexual dysfunction has reported a
small number of studies relating to men, but none relating to women.29
Men taking antipsychotics
report erectile dysfunction, decreased orgasmic quality with delayed, inhibited
or retrograde ejaculation, and diminished interest in sex. Women experience
decreased desire, difficulty achieving orgasm, changes in orgasmic quality and
anorgasmia. Dyspareunia, secondary to oestrogen deficiency, can result in
vaginal atrophy and dryness. Galactorrhea is experienced in both sexes.28
A recent observational
study of schizophrenia found that in patients with diminished sexual desire,
ziprasidone was preferred over olanzapine.30 The
majority of antipsychotics cause sexual dysfunction by dopamine receptor
blockade. This causes hyperprolactinaemia with subsequent suppression of the
hypothalamic–pituitary–gonadal axis and hypogonadism in both sexes. This
decreases sexual desire and impairs arousal and orgasm. It also causes
secondary amenorrhoea and loss of ovarian function in women and low
testosterone in men.31 ,32 Although
poorly understood, other neurotransmitter pathways including histamine
blockade, noradrenergic blockade and anticholinergic effects may also be
affected by antipsychotics.
Before commencing dopamine
receptor antagonists it is useful to establish a baseline prolactin, as
subsequent elevation can then be attributed to the drug. Non-drug induced
causes of hyperprolactinaemia such as pituitary tumours should be considered in
patients on dopamine receptor antagonists.33
Antiepileptics
Sexual dysfunction is
common in patients on antiepileptic drugs.34 Gabapentin
and topiramate have been associated with orgasmic dysfunction in both men and
women, and reduced libido in women.35-37
Contraceptives
Oral contraceptives decrease
circulating free testosterone. It is postulated that this decreases desire in
women, although there is little evidence to support this.38 As
with other disorders, the impact of social context including the relationship,
and fear of pregnancy and sexually transmitted diseases are confounding
influences in clinical reports of the impact of oral contraceptives.
Depot medroxyprogesterone
acetate, used as a contraceptive in women, can cause weight gain, depression,
vaginal atrophy and dyspareunia with decreased libido in up to 15% of women.39-41
Treatments
for cancer
The impact of malignancy
and its treatment on both the individual and his or her partner can have a
significant negative influence on their sexual relationship. Many of the cancer
treatments can lead to sexual dysfunction. As common examples, long-acting
gonadotrophin-releasing hormone agonists used for prostate and breast cancer
result in hypogonadism, with subsequent reduction in sexual desire, erectile
dysfunction in men42, vaginal
atrophy and dyspareunia in women as well as orgasmic dysfunction.34
Drugs for
lower urinary tract symptoms and benign prostatic hyperplasia
Men who present with
symptomatic benign prostatic hyperplasia and lower urinary tract symptoms have
an increased incidence of sexual dysfunction. Overall, 72.2% of men with lower
urinary tract symptoms had erectile dysfunction compared with 37.7% in those
without lower urinary tract symptoms.43 Although
surgery and various therapies can improve lower urinary tract symptoms, some of
these treatments also cause or exacerbate erectile dysfunction and ejaculatory
dysfunction.43
Alpha blockers such as
doxazosin, tamsulosin, terazosin and alfuzosin for benign prostatic hyperplasia
are reported to be no worse than placebo in their effects on sexual function,
although tamsulosin was associated with approximately 10% increase in
ejaculatory dysfunction in treated men.44
Other
drugs that cause sexual dysfunction
Antiandrogens such as
cyproterone acetate, cimetidine, digoxin and spironolactone block the androgen
receptor. This reduces sexual desire in both sexes,45 and
affects arousal and orgasm.
Steroids such as prednisone
used for many chronic inflammatory disorders result in low serum testosterone
which reduces sexual desire and causes erectile dysfunction.46 Immunosuppressive
drugs such as sirolimus and everolimus are widely used in kidney
transplantation and can impair gonadal function and cause erectile dysfunction.47 Protease
inhibitors for HIV have also been implicated in sexual dysfunction and cause
erectile problems in over half of men taking them.48
Many other drugs including
antihistamines, pseudoephedrine, opioids and recreational drugs may cause
sexual dysfunction and should be considered when assessing the patient.
Strategies
to manage sexual dysfunction
Non-drug approaches include
therapy with a clinical psychologist who understands sexual dysfunction. A
variety of strategies have been tried to reverse drug-induced sexual
dysfunction, including drug switching, dose reduction and drug holidays. Taking
a phosphodiesterase type 5 inhibitor in anticipation of intercourse has become
the standard of care for men.49-51 It
improves erections in about 70% of men with hypertension.52 However,
phosphodiesterase type 5 inhibitors are contraindicated in men using nitrates
and should be used with caution in those on alpha blockers, where postural
hypotension can be a problem. In women, sildenafil has shown promise for
reversing the inadequate lubrication and delayed orgasm induced by selective
serotonin reuptake inhibitors.53
Changing to an alternative
drug is recommended for men and women taking antihypertensives. Alpha blockers,
ACE inhibitors and calcium channel blockers are not considered to cause
erectile dysfunction,54 while
several studies have suggested that angiotensin II receptor antagonists may
even improve sexual function. Beta 1 -selective beta
blockers such as nebivolol may have potential advantages in these patients.55
In patients taking
antipsychotics, establish the cause of the hyperprolactinaemia then consider
dose reduction or switching to prolactin-sparing drugs. Relationship
counselling and addressing patient-specific concerns can be useful.28
In women, oestrogen cream
can alleviate local symptoms such as atrophic vaginitis and dyspareunia. If a
woman complains of sexual dysfunction while on an injectable progestogen,
another form of contraceptive can be considered.34
Suggested solutions to
gabapentin-induced anorgasmia include dose reduction, timing of dose away from
planned coitus until anorgasmia no longer occurs, substitution with a different
medication, and co-administration of other medications.35,36
Conclusion
Understanding both the
impact of a disorder and the effects of its treatment on both the patient and
their partner are critical to providing good clinical care. It is important for
the clinician to acknowledge and encourage discussion regarding sexual
function, as well as enquire about the impact of drugs on sexual function. This
will ensure patients and their partners understand their sexual difficulties
and treatment options.
REFERENCES
- Leiblum SR, Rosen RC, editors.
Principles and Practice of Sex Therapy. 3rd ed. The Guilford Press; 2000.
- Levine SB, editor. Handbook of Clinical
Sexuality for Mental Health Professionals. New York: Brunner-Routledge; 2003.
- Conaglen HM, Conaglen JVHow to treat male sexual dysfunction. N Z Dr 2010 June 30;29-34.
- Düsing RSexual
dysfunction in male patients with hypertension: influence of
antihypertensive drugs. Drugs
2005;65:773-86.
- Lambert M,
Conus P, Eide P, Mass R, Karow A, Moritz S, et alImpact of present and
past antipsychotic side effects on attitude toward typical antipsychotic
treatment and adherence. Eur
Psychiatry 2004;19:415-22.
- Cummins T, Miller S. The effects of drug
abuse on sexual functioning. In: Levine SB, editor. Handbook of clinical
sexuality for mental health professionals. New York: Brunner-Routledge; 2003. p. 443-56.
- Gott M,
Hinchliff S, Galena EGeneral practitioner attitudes to discussing sexual
health issues with older people. Soc
Sci Med 2004;58:2093-103.
- Moreira ED Jr,
Brock G, Glasser DB, Nicolosi A, Laumann EO, Paik A, et al Help-seeking
behaviour for sexual problems: the global study of sexual attitudes and
behaviors. Int J Clin Pract
2005;59:6-16 .
- Segraves R. Recognizing and reversing
sexual side effects of medications. In: Levine SB, editor. Handbook of
clinical sexuality for mental health professionals. New York: Brunner-Routledge;
2003. p. 377-91.
- Bacon CG,
Mittleman MA, Kawachi I, Giovannucci E, Glasser DB, Rimm EB Sexual
function in men older than 50 years of age: results from the health
professionals follow-up study. Ann
Intern Med 2003;139:161-8.
- Shabsigh R,
Perelman MA, Lockhart DC, Lue TF, Broderick GAHealth issues of men:
prevalence and correlates of erectile dysfunction. J Urol 2005;174:662-7.
- Doumas M,
Tsakiris A, Douma S, Grigorakis A, Papadopoulos A, Hounta A, et
alBeneficial effects of switching from beta-blockers to nebivolol on the
erectile function of hypertensive patients. Asian J Androl 2006;8:177-82.
- Hanon O, Mounier-Vehier C, Fauvel JP, Marquand A,
Jaboureck O, Justin EP, et al[Sexual dysfunction in treated hypertensive
patients. Results of a national survey]. Arch Mal Coeur Vaiss 2002;95:673-7.
French.
- Hodge RH,
Harward MP, West MS, Krongaard-Demong L, Kowal-Neeley MB Sexual function
of women taking antihypertensive agents: a comparative study. J Gen Intern Med 1991;6:290-4.
- Meston CM,
Gorzalka BB, Wright JMInhibition of subjective and physiological sexual
arousal in women by clonidine. Psychosom
Med 1997;59:399-407.
- Fogari R, Preti
P, Zoppi A, Corradi L, Pasotti C, Rinaldi A, et alEffect of valsartan and
atenolol on sexual behavior in hypertensive postmenopausal women. Am J Hypertens 2004;17:77-81.
- Brill MAntidepressants
and sexual dysfunction. Fertil
Steril 2004;81 Suppl 2:35-40.
- Werneke U,
Northey S, Bhugra DAntidepressants and sexual dysfunction. Acta Psychiatr Scand 2006;114:384-97.
- Baggaley
MSexual dysfunction in schizophrenia: focus on recent evidence. Hum Psychopharmacol 2008;23:201-9.
- Baldwin DSSexual
dysfunction associated with antidepressant drugs. Expert Opin Drug Saf 2004;3:457-70.
- Bostwick JMA
generalist's guide to treating patients with depression with an emphasis
on using side effects to tailor antidepressant therapy. Mayo Clin Proc 2010;85:538-50.
- Williams VS,
Baldwin DS, Hogue SL, Fehnel SE, Hollis KA, Edin HMEstimating the
prevalence and impact of antidepressant-induced sexual dysfunction in 2
European countries: a cross-sectional patient survey. J Clin Psychiatry 2006;67:204-10.
- Montgomery SA,
Baldwin DS, Riley AAntidepressant medications: a review of the evidence
for drug-induced sexual dysfunction. J
Affect Disord 2002;69:119-40.
- Philipp M,
Kohnen R, Benkert OA comparison study of moclobemide and doxepin in major
depression with special reference to effects on sexual dysfunction. Int Clin Psychopharmacol 1993;7:149-53.
- Stahl SMBasic
psychopharmacology of antidepressants, part 1: antidepressants have seven
distinct mechanisms of action. J
Clin Psychiatry 1998;59 Suppl 4:5-14.
- Kennedy SH,
Rizvi SJAgomelatine in the treatment of major depressive disorder:
potential for clinical effectiveness. CNS
Drugs 2010;24:479-99.
- Howland
RHPublication bias and outcome reporting bias: agomelatine as a case
example. J Psychosoc Nurs Ment
Health Serv 2011;49:11-4.
- Kelly DL,
Conley RRSexuality and schizophrenia: a review. Schizophr Bull 2004;30:767-79.
- Berner MM,
Hagen M, Kriston LManagement of sexual dysfunction due to antipsychotic
drug therapy. Cochrane Database Syst
Rev 2007;1:CD003546.
- Lambert M,
Haro JM, Novick D, Edgell ET, Kennedy L, Ratcliffe M, et al Olanzapine vs.
other antipsychotics in actual out-patient settings: six months
tolerability results from the European Schizophrenia Out-patient Health
Outcomes study. Acta Psychiatr Scand
2005;111:232-43.
- Haddad PM,
Wieck AAntipsychotic-induced hyperprolactinaemia: mechanisms, clinical
features and management. Drugs
2004;64:2291-314.
- Knegtering H,
van der Moolen AE, Castelein S, Kluiter H, van den Bosch RJ What are the
effects of antipsychotics on sexual dysfunctions and endocrine
functioning? Psychoneuroendocrinology
2003;28 Suppl 2:109-23.
- Inder WJ,
Castle DAntipsychotic-induced hyperprolactinaemia. Aust N Z J Psychiatry 2011;45:830-7.
- Carey
JCPharmacological effects on sexual function. Obstet Gynecol Clin North Am 2006;33:599-620.
- Clark JD,
Elliott JGabapentin-induced anorgasmia. Neurology
1999;53:2209.
- Grant AC, Oh
HGabapentin-induced anorgasmia in women. Am
J Psychiatry 2002;159:1247.
- Labbate LA,
Rubey RNGabapentin-induced ejaculatory failure and anorgasmia. Am J Psychiatry 1999;156:972.
- Bancroft J,
Sherwin BB, Alexander GM, Davidson DW, Walker AOral contraceptives,
androgens, and the sexuality of young women: II. The role of androgens. Arch Sex Behav
1991;20:121-35.
- Matson SC,
Henderson KA, Mcgrath GJPhysical findings and symptoms of depot
medroxyprogesterone acetate use in adolescent females. J Pediatr Adolesc Gynecol 1997;10:18-23.
- Fraser IS,
Dennerstein GJDepo-Provera use in an Australian metropolitan practice. Med J Aust 1994;160:553-6.
- Heber KRMedroxyprogesterone acetate as an
injectable contraceptive. Aust Fam Physician 1988;17:199-201, 204.
- Berterö
CAltered sexual patterns after treatment for prostate cancer. Cancer Pract 2001;9:245-51.
- Miner M,
Rosenberg MT, Perelman MATreatment of lower urinary tract symptoms in
benign prostatic hyperplasia and its impact on sexual function. Clin Ther 2006;28:13-25.
- Gur S,
Kadowitz PJ, Hellstrom WJGuide to drug therapy for lower urinary tract
symptoms in patients with benign prostatic obstruction: implications for
sexual dysfunction. Drugs
2008;68:209-29.
- Conaglen HM,
Conaglen JVSexual desire in women presenting for antiandrogen therapy. J Sex Marital Ther 2003;29:255-67.
- Macadams MR,
White RH, Chipps BEReduction of serum testosterone levels during chronic
glucocorticoid therapy. Ann Intern
Med 1986;104:648-51.
- Huyghe E,
Zairi A, Nohra J, Kamar N, Plante P, Rostaing LGonadal impact of target of
rapamycin inhibitors (sirolimus and everolimus) in male patients: an
overview. Transpl Int 2007;20:305-11.
- Moreno-Perez
O, Escoin C, Serna-Candel C, Pico A, Alfayate R, Merino E, et al Risk
factors for sexual and erectile dysfunction in HIV-infected men: the role
of protease inhibitors. AIDS
2010;24:255-64.
- Nurnberg HG,
Hensley PL, Gelenberg AJ, Fava M, Lauriello J, Paine S Treatment of
antidepressant-associated sexual dysfunction with sildenafil: a randomized
controlled trial. JAMA
2003;289:56-64.
- Labbate
LAPsychotropics and sexual dysfunction: the evidence and treatments. Adv Psychosom Med 2008;29:107-30.
- Taylor MJ,
Rudkin L, Hawton KStrategies for managing antidepressant- induced sexual
dysfunction: systematic review of randomised controlled trials. J Affect Disord 2005;88:241-54.
- Kloner
RErectile dysfunction and hypertension. Int
J Impot Res 2007;19:296-302.
- Nurnberg HG,
Hensley PL, Heiman JR, Croft HA, Debattista C, Paine S Sildenafil
treatment of women with antidepressant-associated sexual dysfunction: a
randomized controlled trial. JAMA
2008;300:395-404.
- Bradley HA,
Wiysonge CS, Volmink JA, Mayosi BM, Opie LHHow strong is the evidence for
use of beta-blockers as first-line therapy for hypertension? Systematic review and meta-analysis. J Hypertens
2006;24:2131-41.
- Cheng
JWNebivolol: a third-generation beta-blocker for hypertension. Clin Ther 2009;31:447-62..
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