Durante mucho tiempo no había principios uniformes para la Atribución de nombres a los antibióticos https://antibioticos-wiki.es . Más a menudo se les llama por el nombre genérico o especie del producto, con menos frecuencia-de acuerdo con la estructura química. Algunos antibióticos se nombran de acuerdo con el lugar donde se asignó el producto.
Danmedbul.dk
INCIDENCE OF SEXUAL DYSFUNCTION DURING THE PERI- AND POSTMENOPAUSE From the literature it appears that the prevalence of sexual problems Sexual dysfunction in the
in women is high, that the prevalence increases with age, and thatthe menopausal transition has a negative influence on sexuality [2-
peri- and postmenopause
8]. The prevalences of sexual dysfunctions may be underestimatedin several of the surveys cited in the present paper as only sexually
Status of incidence, pharmacological treatment and possible risks
active women are included in the surveys. Hypoactive sexual desire
A secondary publication
is the most frequently reported sexual problem in women, rangingfrom 15-25% in the premenopausal women to 40-50% in the post-
Nina Gregersen, MD1, Pernille Tine Jensen, MD, PhD2 &
menopausal women. Lubrication problems are reported in 10-15%
Annamaria G. Elena Giraldi, MD, PhD3
of the premenopausal women increasing to 25-30% of the postmen-opausal women. Problems with orgasm occur in approximately 20%of all age groups; however, there is a tendency towards a higher fre-quency among the youngest women. Dyspareunia is rare among
1) Department of Urology, Aalborg Hospital, Aarhus University Hospital,2) Herlev University Hospital, Department of Gynecology and Obstetrics,
younger women (approximately 5%), it increases with age but fluc-
3) H:S Rigshospitalet, Sexological Clinic, Division of Sexological Research
tuates greatly among the postmenopausal women. The reported
Correspondence: Nina Gregersen, Blegdalsparken 7 st. tv., DK-9000 Aalborg,
prevalence of dyspareunia in the latter group varies between 12%-
Denmark, E-mail: ninagregersen@dadlnet.dk
Conflicts of Interest: Hired and paid as a consultant by Pfizer, Annamaria Gi-
Thus, there is an association between the menopausal transition,
raldi has been project coordinator and chief responsible in medical trials
age and an increasing prevalence of FSD. However, it remains un-
conducted on the effect of a new selective estrogen receptor modulator and
clear which factors related to the menopause that contribute the
sildenafil on female sexual dysfunction in postmenopausal women. Subse-quent teaching of general practitioners, for which Ms. Giraldi has also been
most to the observed increase. It is known from several studies that
responsible was organized and paid for by Pfizer. Similarly, Pernille Jensen
multiple factors influence female sexuality: The general health of the
received payment as a consultant in the same medical trials.
woman, hormonal changes, the woman’s previous sexual function,partner’s erectile dysfunction, changed life- and partner status, the
woman’s expectation to her sexual life during the peri- and post-menopause and her acceptance of physiological and psychological
The frequency of female sexual dysfunction increases with age, and the men-
During the menopausal transition there is a sudden drop in the
opausal transition has a negative effect on the sexuality. Pharmacological
endogen estrogen level, whereas a gradual decline in the androgen
treatment options for female sexual dysfunction during the peri- and post-
level starts around the age of 25 resulting in a low level around the
menopause include hormone therapy or sildenafil. A limited number of ran-domized, controlled trials have been conducted and evidence suggests that
menopause. It is well known that the postmenopausal low estrogen
systemic hormone therapy with estrogen, estrogen/progesterone, estro-
level produces vaginal atrophy, which predisposes to lubrication
gen/testosterone and tibolone have a positive impact on sexual dysfunction
problems. Few studies have elucidated the prognostic significance of
during the peri- and postmenopause. Further, there is evidence that treat-
a drop in the endogen hormone level for the occurrence of FSD in
ment with local estrogen relieves vaginal dryness and dyspareunia. Recentknowledge on side effects related to hormone therapy necessitates careful
the postmenopause. Dennerstein et al have in their prospective, ob-
evaluation of the indication for hormone therapy and the duration of post-
servational population-based study demonstrated that a drop in se-
menopausal hormone therapy should be as short as possible. Long-term side
rum estradiol is correlated to reduced sexual desire and sexual re-
effects of testosterone have not yet been fully investigated. A positive effect of
sponsivity, defined as arousability, orgasm and sexual pleasure. In
sildenafil has been observed in a limited group of women; those with arousal
the same study there was no correlation between serum androgen
problems but with no desire problems. The results suggest an intensified fo-cus on new pharmaceutical products for the treatment of female sexual dys-
levels and FSD [4, 10]. Minor studies on both pre- and postmeno-
function in the postmenopause. For the time being the effect of testosterone
pausal women as well as women with surgically induced menopause
therapy and tibolone on female sexual dysfunction is being investigated.
have demonstrated a correlation between reduced sexual desire and
Sexual dysfunction in women (Female Sexual Dysfunction, FSD) is
multi-factorial and influenced by physiological, psychological, socialand emotional factors. FSD is defined in four diagnostic groups: de-
PHARMACOLOGICAL TREATMENT
sire-, arousal-, orgasm- and pain problems. Recently, it has been
FSD is traditionally treated with sexological counselling and/or hor-
suggested that the woman herself should assess the dysfunction as
mones. However, within the past years, the successful development
distressful to be diagnosed as having a sexual dysfunction [1]. There
of new pharmacological treatments of erectile dysfunction in men
are only a limited number of well-conducted population surveys on
has resulted in an increasing focus on the development of new phar-
the prevalence of FSD. Further, relatively few randomized, control-
macological treatment options for FSD. Pharmacological treatment
led trials of pharmacological treatment of FSD have been carried
options of FSD in postmenopausal women can be hormonal (estro-
gen, estrogen/progesterone, estrogen/testosterone, and tibolone) ornon-hormonal (sildenafil). Several uncontrolled studies of the effect
of these products on FSD in postmenopausal women have been
A computer-based search in PubMed was conducted with the key
conducted. However, as previously mentioned, we have decided to
words: Sexual function, female sexual dysfunction, sexual dysfunction,
focus on the limited number of randomized, blinded, placebo con-
sexuality, postmenopausal [women], androgen deficiency syndrome,
trolled trials (Table 1). menopause, dyspareunia, vaginal atrophy, vaginal dryness, hormonereplacement therapy (HRT), estrogen, tibolone, sildenafil, Viagra, tes-SYSTEMIC ESTROGEN tosterone and androgen. Papers through 2004-2005 were selected and
Estrogen is fat-soluble and exerts its effect on intracellular receptors.
reviewed for design and content, further using their references to lo-
The estrogen-receptor complex penetrates to the nucleus of the cell
cate other relevant papers. It was decided to focus on randomized,
where it is bound reversibly to the DNA, and then induces mRNA
controlled trials with regard to the effect of pharmacological treat-
synthesis, protein synthesis and mitosis activity. This leads to the ef-
ment of sexual problems during the peri- and postmenopause.
fects of estrogen, among these the proliferation of the vaginal mu-cous membrane. In addition, estrogen receptors are present in other
D A N I S H M E D I C A L B U L L E T I N V O L . 5 3 N O . 3 / A U G U S T 2 0 0 6
Table 1. Overview of randomized, controlled studies of pharmacological treatment of sexual dysfunction in postmenopausal women. Reference Preparation lubrication dyspareunia Dennerstein L et al 1980 (16) . . RCT, DB, PC, CO
Nathorst-Böös J et al 1993 (17). RCT, DB, PC
Kökcü A 2000 (18) . . . . . . . . . . . RCT, SB
Nathorst-Böös J et al 1997 (19). RCT, DB
Wu MH et al 2001 (20) . . . . . . . RCT, SB
Suckling J et al 2003 (21) . . . . . RCT, DB
Sarral P et al 1998 (22) . . . . . . . RCT, DB
Lobo RA et al 2003 (23). . . . . . . RCT, DB
Flöter A et al 2002 (24) . . . . . . . RCT, DB, CO
Shifren JL et al 2000 (25). . . . . . RCT, DB
Buster JE et al 2005 (26) . . . . . . RCT, DB, PC
Simon J et al 2005 (27) . . . . . . . RCT, DB, PC
Laan E et al 2001 (28) . . . . . . . . RCT, DB, PC, CO
Palacios S et al 1995 (29). . . . . . RCT, SB, PC
Basson R et al 2002 (30) . . . . . . RCT, DB, PC
Berman J et al 2003 (31) . . . . . . RCT, DB, PC
Basson R and Brotto L 2003 (32) RCT, DB, PC, CO
RCT = Randomized, controlled study; DB = Double blind; SB = Single blinded; PC = Placebo controlled; CO = Cross-over study; E+T = Estrogen + testosterone; E+P = Estrogen-progesterone; NA = Not Available; ↑: Increase/Improvement; ↓: Decrease; →: No change* A positive effect of tibolone was found on all measured goals, but compared to estrogen-progesterone treatment the only additional effect of tibolone was measured on sexual activity, pleasure and satisfaction.
tissues, e.g. in the central nervous system (CNS), the pituitary gland
ported by studies in which the effect of estrogen has been compared
to other hormone treatments [18-20].
Whether hormone therapy using estrogen/estrogen combined
with progesterone actually does alleviate FSD has been debated for
LOCAL ESTROGEN
many years and remains controversial. Clinical experience and the
Estrogen can be administered vaginally as creams, pessaries, tablets
results of several studies have shown that urogenital discomforts
or estradiol releasing ring. The local administration results in a con-
arising in relation to the menopausal transition can be alleviated
siderable local effect but a minimal systemic effect.
with estrogen. Postmenopausal women treated with estrogen report
A Cochrane review from 2003 of local estrogen treatment of vagi-
less vaginal irritation, vaginal dryness and pain during intercourse.
nal atrophy analyzed 16 studies of 2129 surgically induced or natu-
However, only a limited number of studies have investigated this in a
rally postmenopausal women. Evidence pointed towards that local
randomized design. A study from 1980 on 36 women with surgically
estrogen treatment has a positive effect on vaginal dryness and dys-
induced menopause demonstrated that estrogen-only treatment,
pareunia regardless of application form. However, the tablets dem-
compared with placebo or levonorgestrel, significantly improved the
onstrated significantly better effect compared to either creams or the
women’s sexual desire, lubrication, orgasm frequency and overall
vaginal ring/pessary. None of the treatments altered the sexual de-
sexual pleasure [16]. Nathorst-Böös et al demonstrated in a large
study from 1993 of 239 naturally postmenopausal women that es-trogen-only treatment significantly increased the frequency of sex-
SYSTEMIC ESTROGEN AND ANDROGEN
ual activity and sexual fantasies, improved the level of sexual pleas-
Like estrogen, testosterone is a steroid which crosses the cell mem-
ure and vaginal lubrication, and decreased dyspareunia compared to
brane and is bound to intracellular receptors after being trans-
placebo [17]. Hence, only a limited number of randomized trials
formed into dihydrotestosterone. Subsequently, the receptor-hor-
have investigated the effect of estrogen treatment on the sexual func-
mone complex penetrates the nucleus of the cell resulting in protein
tion in comparison to placebo. However, both studies show a posi-
synthesis. Like estrogen receptors, testosterone receptors are present
tive effect. The positive effect of estrogen on FSD is further sup-
both in peripheral tissues and in the CNS.
D A N I S H M E D I C A L B U L L E T I N V O L . 5 3 N O . 3 / A U G U S T 2 0 0 6
Results from several studies suggest that testosterone may have a
was only superior regarding sexual satisfaction and pleasure [19].
positive effect on FSD in the postmenopause. There are currently no
Two minor randomized studies have demonstrated that tibolone
registered hormone products with a combination of estrogen and
compared to estrogen-progesterone treatment incurs better results
testosterone or testosterone-only, for the treatment of menopausal
on sexual desire and dyspareunia [18, 20].
symptoms. Despite this, estrogen/testosterone combinations havebeen used off-label for some years (e.g. in the United Kingdom, the
SILDENAFIL
Sildenafil is a phosphodiesterase 5 inhibitor (PDE5-inhibitor),
Currently, there is an on-going discussion about the existence of
which relaxes smooth muscle cells through the nitric oxide/cyclic
an androgen deficiency syndrome, particularly in women with men-
guanosine monophosphate (cGMP) system. Sildenafil increases the
opause induced by surgery, radiotherapy, or chemotherapy. Clinical
vaginal blood flow leading to increased lubrication. At this back-
observations suggest that the initial positive effect of estrogen treat-
ground sildenafil can theoretically be expected to increase sexual
ment on FSD decreases with time. Based on these observations sev-
pleasure and satisfaction in women with lubrication problems.
eral studies have been conducted, to investigate the effect of estrogen
A randomized study of 204 naturally postmenopausal women,
and testosterone in different administration forms on FSD.
who were experiencing sexual problems and not receiving any hor-
In 1998 Sarrel conducted a study of 20 surgically induced or natu-
mone supplements, demonstrated that sildenafil treatment com-
rally postmenopausal women. Despite estrogen/estrogen-progester-
pared to placebo did not result in improved sexual function regard-
one treatment, all women still had menopausal symptoms, lubrica-
ing lubrication, genital sensitivity, sexual pleasure or satisfaction
tion problems, dyspareunia and reduced sexual desire. Following a
with sexual life [30]. The lack of effect of sildenafil in this particular
two week wash-out placebo period, the effect of estrogen-only treat-
study can be attributed to the fact that the test group was very heter-
ment versus estrogen + testosterone treatment was investigated.
ogeneous: All included women were complaining of arousal prob-
Compared to the group receiving the estrogen-only treatment, the
lems, but this was only the primary problem in approximately 50%
group receiving the combination of testosterone and estrogen treat-
of the women. Subsequent studies with sildenafil were conducted on
ment reported a significant improvement in sexual desire. However,
women primarily experiencing arousal and orgasm problems. Ber-
there was no effect on lubrication and dyspareunia suggesting that
man et al observed the effect of sildenafil on FSD in 192 surgically
these are primarily influenced by estrogen [22]. In a recent, double-
induced or naturally postmenopausal women. The women were re-
blind randomized study of 218 surgically or naturally induced post-
ceiving HRT in the form of estrogen/estrogen-progesterone. Moreo-
menopausal women with hypoactive sexual desire, it was found that
ver, women with low levels of plasma testosterone, received testo-
estrogen and methyltestosterone treatment significantly increased
sterone treatment. The study showed that in women with arousal
both the level and frequency of the women’s sexual desire compared
problems but no concomitant desire problems sildenafil improved
to the estrogen-only treatment. These findings suggest a positive ef-
genital sensitivity, lubrication, subjective arousal, orgasm and satis-
fect of the androgen component of the combination treatment [23].
faction with intercourse, whereas there was no effect on those
A randomized cross-over study of 44 surgically induced menopausal
women who also experienced desire problems. The same study
women showed that treatment with estrogen-testosterone signifi-
showed no effect on desire and dyspareunia [31]. Basson & Brotto
cantly improved sexual desire and pleasure compared to estrogen
investigated 34 naturally postmenopausal women receiving estro-
treatment only [24]. Finally, a randomized cross-over study of 65
gen-progesterone treatment for diagnosed arousal and orgasm
surgically induced menopausal women, continually receiving estro-
problems. The study demonstrated that sildenafil did not improve
gen treatment, demonstrated that transdermal testosterone treat-
orgasm and subjective sexual arousal, even though it was objectively
ment significantly improved sexual activity and pleasure/orgasm
measured that sildenafil increased the blood flow to the vagina dur-
while sexual desire and arousability were not significantly improved
[25]. Two large studies of 562 and 533 surgically induced menopau-
In conclusion, the above studies only demonstrate a positive effect
sal women with hypoactive sexual desire disorder have recently been
of sildenafil in a selected group of women, i.e. those with arousal
reported. They showed that women receiving testosterone (300
problems and no concurrent desire problems. The manufacturers of
µg/day) as a transdermal patch together with concomitant oral es-
the product have decided to no longer test sildenafil for treatment of
trogen experienced a statistically significant increase in the fre-
sexual problems in women. It therefore remains uncertain whether
quency of total satisfying sexual activity, as well as a statistically sig-
there would be any beneficial effects in women experiencing sexual
nificant increase in sexual desire when compared to estrogen-only
problems due to diseases like depression, diabetes or adverse events
therapy. Significant improvements were also seen in arousal, or-
gasm, pleasure, responsiveness, concerns, self-image and distresslevels for women using the female testosterone patch. Overall, ad-
RISKS RELATED TO PHARMACOLOGICAL TREATMENT
verse events were similar in the testosterone and placebo groups. Al-
Recently, adverse events to HRT have been evaluated in several large
though the overall incidence of androgenic adverse events was low,
studies [33-37]. They found that HRT increased the risk of ischemic
the incidence was slightly higher in the testosterone group [26, 27].
heart disease, breast cancer, stroke and pulmonary embolism. Theduration of the treatment as well as socio-economic status and the
TIBOLONE
presence of diabetes were significant prognostic factors regarding
Tibolone is a synthetic steroid with estrogenic- and gestagenic ef-
these complications. Treatment with tibolone seems to be associated
fects as well as a weak androgenic effect. The effect of tibolone on
with a lower risk of developing breast cancer compared to HRT with
FSD has also been tested. Two minor, randomized placebo control-
estrogen and progesterone but a higher risk than treatment with es-
led trials have demonstrated a positive effect of tibolone regarding
trogen-only [33]. However, recently a multicenter study investigat-
sexual desire, lubrication and orgasm, whereas only one of the stud-
ing the use of tibolone for treatment of osteoporosis in elderly
ies has demonstrated a positive effect on dyspareunia [28, 29]. To in-
women have been terminated as there were indications of a higher
vestigate whether the androgenic effect of tibolone makes it superior
risk of stroke in the tibolone group compared to placebo [38]. These
to estrogen/estrogen-progesterone treatment regarding FSD, Nath-
studies have prompted a revised official recommendation from the
orst-Böös & Hammar conducted a randomized controlled study in
Danish Medicines Agency advising that short-term hormone ther-
315 naturally postmenopausal women. An improvement was ob-
apy in relation to substantial discomforts experienced during and
served in the tibolone arm regarding all measured endpoints: Sexual
after the menopausal transition is still well-founded. Clinical rec-
desire, lubrication, orgasm, pain and overall sexual satisfaction.
ommendations from the Danish Society of Obstetrics and Gynae-
However, comparing tibolone to estrogen-progesterone, tibolone
cology state that hormone supplements can be applied to release
D A N I S H M E D I C A L B U L L E T I N V O L . 5 3 N O . 3 / A U G U S T 2 0 0 6
FSD after the menopause [39]. The need for hormone treatment
8. Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States:
must be carefully assessed on an individual basis, taking into ac-
prevalence and predictors. JAMA 1999; 281:537-44.
count possible risks relating to the individual woman. The lowest
9. Avis NE, Stellato R, Crawford S et al. Is there an association between
menopause status and sexual functioning? Menopause 2000; 7:297-309.
possible dose should be used and the treatment duration should be
10. Dennerstein L, Randolph J, Taffe J et al. Hormones, mood, sexuality, and
the menopausal transition. Fertil Steril 2002; 77 Suppl 4:S42-8.
Adverse events related to local estrogen treatment are rare, but no
11. Dennerstein L, Lehert P. Modeling mid-aged women’s sexual function-
studies have evaluated long-term effects beyond six months. One
ing: a prospective, population-based study. J Sex Marital Ther 2004;30:173-83.
study has demonstrated that the use of estrogen cream was corre-
12. Davis S. Testosterone deficiency in women. J Reprod Med 2001; 46(3
lated with a significant increase in vaginal bleedings, breast tension
and perianal pain compared to vaginal estradiol tablets [21].
13. Guay A, Jacobson J, Munarriz R et al. Serum androgen levels in healthy
Treatment with testosterone is based on the principle that serum
premenopausal women with and without sexual dysfunction: Part B: Re-
levels of testosterone should be kept within upper normal range;
duced serum androgen levels in healthy premenopausal women withcomplaints of sexual dysfunction. Int J Impot Res 2004; 16:121-9.
thereby unwanted adverse events are believed to be minimized. Po-
14. Guay AT, Jacobson J. Decreased free testosterone and dehydroepiandros-
tential adverse events are acne, weight gain, hirsutism, voice changes
terone-sulfate (DHEA-S) levels in women with decreased libido. J Sex
and serum lipid changes. Few adverse events have been reported in
Marital Ther 2002; 28 Suppl 1:129-42.
those controlled studies published on testosterone treatment, given
15. Floter A, Nathorst-Boos J, Carlstrom K et al. Androgen Status and Sexual
Life in Perimenopausal Women. J North Am Menopause Soc 1997; 4:95-
that the serum testosterone has been kept within the normal physio-
logical level [26, 27, 41]. However, future studies are to evaluate pos-
16. Dennerstein L, Burrows GD, Wood C et al. Hormones and sexuality: ef-
fect of estrogen and progestogen. Obstet Gynecol 1980; 56:316-22.
The adverse event profile of sildenafil is similar in women and
17. Nathorst-Boos J, Wiklund I, Mattsson LA et al. Is sexual life influenced
men: Headache, facial flushing, dizziness, rhinitis, upper dyspep-
by transdermal estrogen therapy? A double blind placebo controlledstudy in postmenopausal women. Acta Obstet Gynecol Scand 1993;
sia and visual disturbances. The adverse events are described as mild
and transient in the present cited studies [30-32].
18. Kokcu A, Cetinkaya MB, Yanik F et al. The comparison of effects of tibo-
lone and conjugated estrogen-medroxyprogesterone acetate therapy on
CONCLUSION
sexual performance in postmenopausal women. Maturitas 2000; 36:75-80.
The prevalence of FSD increases with age and menopause is an inde-
19. Nathorst-Boos J, Hammar M. Effect on sexual life – a comparison be-
tween tibolone and a continuous estradiol-norethisterone acetate regi-
prognostic factor for developing FSD. The causal relations have
not yet been documented, but it is suggested that hormonal factors
20. Wu MH, Pan HA, Wang ST et al. Quality of life and sexuality changes in
such as reduced serum estrogen- and androgen levels are of impor-
postmenopausal women receiving tibolone therapy. Climacteric 2001;4:314-9.
21. Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in
The treatment of FSD in postmenopausal women should be based
postmenopausal women. Cochrane Database Syst Rev 2003;:CD001500.
on an individual assessment where the points of reference are the
22. Sarrel P, Dobay B, Wiita B. Estrogen and estrogen-androgen replacement
woman’s subjective discomforts, risk factors and potential underly-
in postmenopausal women dissatisfied with estrogen-only therapy. Sex-ual behavior and neuroendocrine responses. J Reprod Med 1998; 43:847-
ing causes of the problem. If pharmacological treatment of FSD is
deemed indicated, several randomized studies have demonstrated a
23. Lobo RA, Rosen RC, Yang HM et al. Comparative effects of oral esteri-
positive effect of systemic hormone therapy with estrogen/estrogen-
fied estrogens with and without methyltestosterone on endocrine pro-
progesterone, combined estrogen and androgen as well as with tibo-
files and dimensions of sexual function in postmenopausal women with
lone. Moreover, local estrogen therapy has demonstrated a positive
hypoactive sexual desire. Fertil Steril 2003; 79:1341-52.
24. Floter A, Nathorst-Boos J, Carlstrom K et al. Addition of testosterone to
effect on vaginal dryness and dyspareunia. One study has demon-
estrogen replacement therapy in oophorectomized women: effects on
strated a significant effect of sildenafil on lubrication problems in
sexuality and well-being. Climacteric 2002; 5:357-65.
women who are not also experiencing hypoactive sexual desire dis-
25. Shifren JL, Braunstein GD, Simon JA et al. Transdermal testosterone
treatment in women with impaired sexual function after oophorectomy. N Engl J Med 2000; 343:682-8.
The known side effects of hormone therapy and the compara-
26. Buster JE, Kingsberg SA, Aguirre O et al. Testosterone patch for low sex-
tively sparse effect of sildenafil necessitate an intensified focus on
ual desire in surgically menopausal women: a randomized trial. Obstet
new areas in the field of pharmacological treatment options of FSD.
Internationally, most research is being conducted with testosterone
27. Simon J, Braunstein G, Nachtigall L et al. Testosterone patch increases
but the risk of potential side effects demands long-term follow-up.
sexual activity and desire in surgically menopausal women with hypoac-tive sexual desire disorder. J Clin Endocrinol Metab 2005; 90:5226-33.
In addition ongoing studies investigate the effect of tibolone on hy-
28. Laan E, van Lunsen RH, Everaerd W. The effects of tibolone on vaginal
poactive sexual desire and lubrication problems in postmenopausal
blood flow, sexual desire and arousability in postmenopausal women.
29. Palacios S, Menendez C, Jurado AR et al. Changes in sex behaviour after
menopause: effects of tibolone. Maturitas 1995; 22:155-61. Referencea
30. Basson R, McInnes R, Smith MD et al. Efficacy and safety of sildenafil ci-
1. Basson R, Berman J, Burnett A et al. Report of the international consen-
trate in women with sexual dysfunction associated with female sexual
sus development conference on female sexual dysfunction: definitions
arousal disorder. J Womens Health Gend Based Med 2002; 11:367-77.
and classifications. J Urol 2000; 163:888-93.
31. Berman JR, Berman LA, Toler SM et al. Safety and efficacy of sildenafil
2. Bachmann GA, Leiblum SR. The impact of hormones on menopausal
citrate for the treatment of female sexual arousal disorder: a double-
sexuality: a literature review. Menopause 2004; 11:120-30.
blind, placebo controlled study. J Urol 2003; 170:2333-8.
3. Castelo-Branco C, Blumel JE, Araya H et al. Prevalence of sexual dys-
32. Basson R, Brotto LA. Sexual psychophysiology and effects of sildenafil ci-
function in a cohort of middle-aged women: influences of menopause
trate in oestrogenised women with acquired genital arousal disorder and
and hormone replacement therapy. J Obstet Gynaecol 2003; 23:426-30.
impaired orgasm: a randomised controlled trial. BJOG 2003; 110:1014-
4. Dennerstein L, Dudley E, Burger H. Are changes in sexual functioning
during midlife due to aging or menopause? Fertil Steril 2001; 76:456-60.
33. Beral V. Breast cancer and hormone-replacement therapy in the Million
5. Dennerstein L, Hayes R. Confronting the challenges: epidemiological
Women Study. Lancet 2003; 362:419-27.
study of female sexual dysfunction and the menopause. J Sex med 2005;
34. Nelson HD, Humphrey LL, Nygren P et al. Postmenopausal hormone re-
placement therapy: scientific review. JAMA 2002; 288:872-81.
6. Fugl-Meyer AR, Fugl-Meyer KS. Sexual Disabilities, problems and satis-
35. Rossouw JE, Anderson GL, Prentice RL et al. Risks and benefits of estro-
faction in 18-74 year old swedes. Scand J Sexol 1999; 2:79-97.
gen plus progestin in healthy postmenopausal women: principal results
7. Koster A, Eplov LF, Garde K. Anticipations and experiences of meno-
From the Women’s Health Initiative randomized controlled trial. JAMA
pause in a Danish female general population cohort born in 1936. Arch
D A N I S H M E D I C A L B U L L E T I N V O L . 5 3 N O . 3 / A U G U S T 2 0 0 6
36. Lokkegaard E, Pedersen AT, Heitmann BL et al. Relation between hor-
mone replacement therapy and ischaemic heart disease in women: pro-spective observational study. BMJ 2003; 326:426.
37. Lokkegaard E, Jovanovic Z, Heitmann BL et al. Increased risk of stroke in
hypertensive women using hormone therapy: analyses based on the Dan-ish Nurse Study. Arch Neurol 2003; 60:1379-84.
38. www.dkma.dk. Discontinuation of a clinical trial of Livial® (tibolone).
39. Andersen LF FAGELONLPAPAPE. Guidelines concerning peri- and
postmenopausal hormon therapy (in Danish) http://www.dsog.dk/files/Guidelines_HT_23_01_05.pdf. 2005.
40. Laegemiddelstyrelsen. Alvorlige bivirkninger fører til ændrede ret-
ningslinier for brugen af hormonbehandling i EU (in Danish). http://www.laegemiddelstyrelsen.dk/1024/visLSArtikel.asp?ar-tikelID=1826. 2003.
41. Bachmann G, Bancroft J, Braunstein G et al. Female androgen insuffi-
ciency: the Princeton consensus statement on definition, classification,and assessment. Fertil Steril 2002; 77:660-5.
D A N I S H M E D I C A L B U L L E T I N V O L . 5 3 N O . 3 / A U G U S T 2 0 0 6
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In vitro models for the determination of drug mode of action IBAM GbR Dr. Rainer Knörle & Dr. Peter SchnierleFerdinand-Porsche-Str. 5, 79211 Denzlingen Our service offering includes several models for the identification of the molecular targets of a drug and of its off-target effects It has been shown that melanin a pigment found in the skin and other parts of the body has an ability