ORIGINAL ARTICLE

E n d o c r i n e C a r e

Sexuality and Fertility in Women with Addisons

Disease

Martina M. Erichsen, Eystein S. Husebye, Trond M. Michelsen, Alv. A. Dahl,

and Kristian Lvs
Department of Medicine (M.M.E., E.S.H., K.L.), Haukeland University Hospital, N-5021 Bergen, Norway;
Institute of Medicine (M.M.E., E.S.H., K.L.), University of Bergen, N-5007 Bergen, Norway; Department
of Gynecology (T.M.M.), Rikshospitalet, Oslo University Hospital, N-0027 Oslo, Norway; National
Resource Centre for Womens Health (T.M.M.), Oslo University Hospital, N-0027 Oslo, Norway;
Department of Gynecology (T.M.M.), Srlandet Hospital, N-4809 Arendal, Norway; The Norwegian
Radium Hospital (A.A.D.), Oslo University Hospital, N-0310 Oslo, Norway; and University of Oslo
(A.A.D.), N-0316 Oslo, Norway

Context: Females with primary adrenal insufficiency (Addisons disease) have reduced levels of
circulating androgens, which are allegedly important for sexual functioning.

Objective: The aim was to determine peripheral androgen status, sexual functioning, and birth
rates in Addisons disease females.

Design: In a postal survey, all 269 females in the Norwegian Addisons registry were invited to
complete the Sexual Activity Questionnaire (SAQ) and registration of childbirths. Blood samples
were analyzed for 5-androstane-3,17-diol-3-glucuronide (3-Diol-G) and compared with blood
donor levels. The SAQ scores were compared with 740 age-matched controls from the general
population and 234 women subjected to risk-reducing salpingo-oophorectomy. Fertility was es-
timated as standardized incidence ratio for birth; the expected number of births was estimated
from population statistics.

Results: The SAQ was completed by 174 (65%) of the Addisons patients. Those not taking DHEA
had significantly lower 3-Diol-G levels than blood donors (mean, 0.53 vs. 2.2 ng/ml; P 0.0001),
whereas those on DHEA treatment had elevated levels (mean, 5.8 vs. 2.2 ng/ml; P 0.002). The
Addisons disease females were equally sexually active as the controls, but they reported signifi-
cantly higher pleasure and less discomfort. They reported lower pleasure but less discomfort than
the risk-reducing salpingo-oophorectomy women. The fertility was significantly reduced in fe-
males with Addisons disease; 54 children were born to mothers with established diagnosis (87.5
expected), yielding a standardized incidence ratio for birth of 0.69 (confidence interval, 0.52 0.86).

Conclusion: Despite androgen depletion, females with Addisons disease do not report im-
paired sexuality. The fertility is reduced after the diagnosis is made; the reasons for this remain
unknown. (J Clin Endocrinol Metab 95: 4354 4360, 2010)

rimary adrenal insufficiency (Addisons disease) is cortex. Even with state-of-the-art replacement therapy
P characterized by deficiency of cortisol, aldosterone,
and adrenal androgen hormonal precursors, mainly de-
with mineralocorticoids and glucocorticoids, patients
with Addisons disease consistently show reduced health-
hydroepiandrosterone (DHEA) and DHEA sulfate, usu- related quality of life (13). It has been speculated that lack
ally caused by an autoimmune reaction toward the adrenal of androgens contributes to this reduction, but studies

ISSN Print 0021-972X ISSN Online 1945-7197 Abbreviations: CI, Confidence interval; DHEA, dehydroepiandrosterone; 3-Diol-G, 5-
Printed in U.S.A. androstane-3,17-diol-3-glucuronide; ES, effect size; 17OH, 17-hydroxylase; 21OH, 21-
Copyright 2010 by The Endocrine Society hydroxylase; RRSO, risk-reducing salpingo-oophorectomy; SAQ, Sexual Activity Question-
doi: 10.1210/jc.2010-0445 Received February 23, 2010. Accepted June 1, 2010. naire; SCC, side-chain cleavage enzyme; SIR, standardized incidence ratio; TFR, total
First Published Online July 7, 2010 fertility rate.

4354 jcem.endojournals.org J Clin Endocrinol Metab, September 2010, 95(9):4354 4360

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J Clin Endocrinol Metab, September 2010, 95(9):4354 4360 jcem.endojournals.org 4355

aimed at replacing DHEA have shown small and incon- With this background, the aim of the current study was
sistent effects (2, 4 6). to establish the androgen status in a large group of women
The androgen levels in females with Addisons disease with well-characterized Addisons disease as assayed by
have not been described in detail. One reason is that the 3-Diol-G and further explore their sexual function and
commonly used assays for androgen hormones are de- birth rates.
signed for male levels and are therefore unsuitable for as-
sessing the low levels found in females (7). Arlt et al. (4)
and Lvs et al. (6) showed that serum concentrations of Patients and Methods
androgen precursors and testosterone were all below the
normal ranges in a group of women with primary or sec- Patients
Females (n 269; age range, 20 79 yr) with Addisons dis-
ondary adrenal insufficiency. Moreover, the concentra-
ease identified in a national survey of Addisons disease in Nor-
tion of circulating androgens may not reflect the effects on way (3) were invited to participate in the current study. The
the cellular level, and the androgen production in periph- diagnosis had been verified by scrutiny of the medical records of
eral tissues may be better reflected by the level of the tes- all the patients. They had previously given blood samples that
tosterone metabolites androstandione glucuronide, 5- could be analyzed for 3-Diol-G and adrenal autoantibodies.
androstane-3,17-diol-3-glucuronide (3-Diol-G), and The patients were contacted by mail and asked to complete the
Sexual Activity Questionnaire (SAQ) (17) and a registration
3-diol-17G (8), which have not previously been assayed form asking for information concerning premature ovarian in-
in females with Addisons disease. sufficiency, ongoing sex hormone therapy, duration of Addi-
Whether women with Addisons disease have low li- sons disease, and the number of childbirths.
bido or impaired sexual function is not known. Compar-
isons between patients and controls from the general pop- Controls
ulation are mandatory to evaluate data, but have not been This study used three groups of controls: 1) Control subjects
performed. In the studies where sexual function in these for the SAQ ratings were available from a previous study of the
general Norwegian population (18). Five control subjects for
patients has been addressed, comparisons have been made each patient were matched for age in 5-yr intervals. 2) SAQ data
between patient groups, or before and after an interven- were also available from 234 women [mean age, 53.5 (SD, 9.2) yr]
tion. Such studies were often performed with supraphysi- who had chosen risk-reducing salpingo-oophorectomy (RRSO)
ological doses of testosterone (9, 10) or DHEA (11, 12) because of increased hereditary risk for breast and ovarian cancer.
given to the patients. Different designs, time scales, dos- These women were considered an apt control group, with normal
levels of adrenal androgens and variable degree of estrogen defi-
ages, and methods of measurements for sexual functions ciency. 3) Control subjects for 3-Diol-G measurements were 114
have been used, rendering comparisons of the studies dif- anonymous female blood donors aged 20 to 70 yr.
ficult. One DHEA replacement trial in adrenal insuffi-
ciency (both primary and secondary) showed improved SAQ
female sexual function (4), but this was not replicated in We used the Norwegian translation of the SAQ developed by
four other studies (2, 5, 13, 14). In severe androgen-defi- Thirlaway et al. (17) (permission was granted from copyright
cient women due to hypopituitarism, Miller et al. (15) holder L. Fallowfield). The SAQ has been widely used to assess
the impact of various treatments on female sexual functioning
showed improved sexual function with testosterone treat- (19 22). The SAQ has three sections that describe relationship
ment. Overall, the effect of androgen replacement on sex- status, reasons for sexual inactivity, and sexual functioning. The
ual function remains uncertain in women with Addisons latter section measures pleasure and discomfort associated with
disease. sexual intercourse and changes in the frequency of sexual activ-
As for sexuality, the fertility of patients with autoim- ities (habit). Normative data have been collected for the Nor-
wegian version of the SAQ (18).
mune adrenal failure has not been studied systematically.
Reduced fertility is associated with premature gonadal in-
Assays
sufficiency (16), and in a Norwegian registry study we The androgen metabolite 3-Diol-G was assayed by ELISA
found that 7% of women with autoimmune Addisons (DRG Instruments GmbH, Marburg, Germany). Antibodies
disease had premature ovarian insufficiency (3). Autoan- against 21-hydroxylase (21OH), side-chain cleavage enzyme
tibodies against the enzymes side chain cleavage enzyme (SCC), and 17-hydroxylase (17OH) were assayed by methods
(anti-SCC) and 17-hydroxylase (anti-17OH) are more fre- based on an in vitro transcription and translation of antigen as
described by Oftedal et al. (23).
quently found in the Addisons women with premature
ovarian failure and can therefore be used as predictors.
Fertility
Otherwise, it is not known whether patients with Addi- The participants reported the year of diagnosis of Addisons
sons disease have altered fertility compared with the gen- disease, as well as the number and year of their childbirths. Self-
eral female population. reported premature menopause (age 40 yr) was interpreted as

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4356 Erichsen et al. Female Sexuality and Fertility in Addisons Disease J Clin Endocrinol Metab, September 2010, 95(9):4354 4360

premature ovarian insufficiency. The total fertility rate (TFR)

TABLE 1. Characteristics of female Addisons disease
was calculated for the Addisons patients; TFR is the average
number of children a woman would bear during her lifetime if
patients
she were to experience the prevailing age-specific fertility rates of Age <50 Age 50
women. The TFR was calculated for all fertile years but was yr yr All
separated to describe the fertile years before and after the diag- n 70 88 158
nosis. The TFR was also calculated for the Addisons women Age (yr), mean 40.0 (7.1) 62.4 (9.9) 52 (14.14)
with the subgroup of self-reported premature ovarian insuffi- Age (yr), median 41 (19 49) 60 (50 87) 52 (19 87)
ciency excluded. The standardized incidence ratio (SIR) for birth (range)
Age at diagnosis (yr) 29 (7.1) 42 (9.9) 36 (14.1)
is the ratio between the number of observed and expected chil-
Duration of 11 (8.1) 20 (14.4) 16 (14.5)
dren in the patient group. Addisons (yr)
Treatment, n (%)
Statistical analysis DHEA 3 (4.3) 10 (11.4) 13 (8.2)
Oral contraceptives 3 (4.3) 0 (0) 3 (1.9)
The biochemical data and the questionnaire responses are
Hormone 9 (12.9) 15 (17.0) 24 (15.2)
presented with descriptive statistics, and groups are compared replacement
with the Mann-Whitney U test. Antibody-positive fractions were therapy
compared with the 2 test. The 3-Diol-G values in patients and Self-reported history 6 (8.6) 17 (19.3) 23 (15.2)
controls were compared with linear regression analysis, with age of premature ovarian
insufficiency, n (%)
as the independent variable. Statistically significant group dif-
ferences in the SAQ responses were examined for clinical signif- Data are presented as mean (SD), unless described otherwise.
icance with effect sizes (ESs). For continuous variables, we used
Cohens coefficient d, and for 2 2 contingency tables we used
the differences between arcsine transformed proportions (24); positive, and 5.3% anti-SCC positive. Two patients had
ES values of at least 0.40 were considered clinically significant autoimmune polyendocrine syndrome type 1, of whom
based on the recommendations of Cohen (25). All tests were one was anti-SCC antibody positive. Thirteen patients
two-sided, and the significance level was set at P 0.05. Statis-
(8%) were on DHEA therapy, with doses ranging from
tics Norway provided age-specific fertility rates, which were used
for the calculation of expected number of births among the pa- 10 to 50 mg/d.
tients. Data are given with 95% confidence intervals (CIs), con-
sidered significantly different statistically from normal if the CI SAQ findings
does not include 1.00. The SAQ was answered by 65% (174 of 269) of the
female Addisons patients. The nonresponders were
Ethics slightly older (59 yr; SD, 18) than the responders and had
The current study was approved by the Regional Committee had the Addisons diagnosis for 20.9 yr (SD, 13.7). Due to
for Medical Ethics of Western Norway and by the National Data
unreadable signatures on consent forms, 15 SAQs were
Inspectorate. All of the patients gave written informed consent.
The population-based study of the SAQ was approved by the rejected from further analysis, and 11 participants
Regional Committee for Medical Ethics of Eastern Norway, and lacked a logic pattern in their ratings and were also
because the data collection was anonymous, no written informed excluded. The 148 patients with valid SAQ scores were
consent was needed. The study of women who had RRSO was significantly more sexually active, and they scored sig-
approved by the Regional Committee for Medical Ethics of East-
nificantly better on both sexual pleasure and discomfort
ern Norway and by the National Data Inspectorate, and all pa-
tients gave written informed consent. compared with the 740 controls (Table 2). The differ-
ence was considered clinically significant for pleasure
(ES, 0.57) and discomfort (ES, 0.82), but not for sexual
Results activity (ES, 0.23) (clinically significant ES; see Statis-
tical analysis). Compared with the 234 RRSO women,
Patients the Addisons patients showed lower pleasure but sig-
The patient characteristics are summarized in Table nificantly less discomfort.
1. Almost all (91%) had 21OH autoantibody-verified The most common reason for sexual inactivity in
autoimmune Addisons disease, 13% had 17OH anti- both Addisons patients and normative controls was
bodies, and 12% had SCC antibodies. Twenty-three lack of partner (Table 2). No significant differences
women (15%) reported a history of premature ovarian were observed between patients and controls concern-
insufficiency (before age 40 yr), of whom 50% used ing their reasons for sexual inactivity. The SAQ re-
estrogen replacement therapy and 13% used DHEA. All ported that sexual activity of the participants using
had anti-21OH, whereas 48% had anti-SCC, and 26% DHEA was not different from those not using DHEA
had anti-17OH. The antibody frequencies were lower in (data not shown). There was no significant correlation
women with no history of premature ovarian insuffi- between the 3-Diol-G levels and sexual activity or
ciency, with 89% anti-21OH positive, 11% anti-17OH pleasure (data not shown).

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J Clin Endocrinol Metab, September 2010, 95(9):4354 4360 jcem.endojournals.org 4357

TABLE 2. SAQ findings in Addisons patients aged 19 to 87 yr and age-matched controls and women who had
undergone RRSO (age adjusted)
P value
Addisons Age-matched RRSO Patients Patients
SAQ variables patients controls controlsa vs. controls vs. RRSO
Sexual activity n 148 n 740 n 234 0.02 0.05
Active 115 (78) 503 (68) 198 (85)
Inactive 33 (22) 237 (32) 36 (15)
Reasons for inactivity n 33 n 237 n 36
No current partner 15 (46) 124 (52) 19 (8) 0.46 0.45
Too tired 8 (24) 41 (17) 7 (3) 0.33 0.22
Partner too tired 6 (18) 23 (10) 2 (1) 0.14 0.05
Lack of interest 12 (36) 61 (26) 9 (4) 0.20 0.08
Partner not interested in sex 5 (15) 33 (14) 5 (12) 0.79 0.53
Physical problem 4 (12) 17 (7) 1 (0) 0.30 0.09
Partners physical problem 4 (12) 24 (10) 2 (1) 0.76 0.27
Other reasons 8 (24) 62 (26) 5 (2) 0.81 0.15
No. of reasons for inactivity 0.47 0.30
One 17 (52) 138 (58) 23 (64)
Two or more 16 (48) 99 (42) 13 (36)
Frequency of sexual activity n 115 n 503
compared to before
More frequent 12 (10) 27 (5) NA 0.06
Same or less frequent 103 (90) 470 (95)
Pleasure, mean (SD)b 15.2 (5.0) 17.8 (4.5) 14.0 (5.2) 0.001 0.09
Discomfort, mean (SD)c 4.0 (2.0) 2.8 (1.3) 3.7 (1.8) 0.001 0.02
Data represent number (percent). NA, Not applicable because of lack of data due to a printing error of the SAQ in the RRSO study.
a
Adjusted for age.
b
Lower score represents more pleasure.
c
Lower score represents more discomfort.

Fertility significantly elevated 3-Diol-G levels compared with the

Before being diagnosed with Addisons disease, the blood donors (mean, 5.8 vs. 2.2 ng/ml; P 0.002; Mann-
women had 229 children, whereas 236 were expected, Whitney U test). Women with self-reported history of pre-
yielding a SIR for birth at 0.97 (CI, 0.8451.095). For the mature ovarian insufficiency had significantly lower val-
fertile years after the diagnosis was made, the observed
and expected numbers of births were 54 and 87.5, respec-
tively, yielding SIR for birth of 0.69 (CI, 0.52 0.86).
When 23 patients with premature ovarian insufficiency
were excluded, the SIR for birth was 0.72 (CI, 0.52 0.92).
Eight women were diagnosed during pregnancy or in their
postpartum period. Another two women reported that
they were diagnosed with Addisons disease within 1 yr
after delivery and retrospectively confirmed that they were
suffering from adrenal deficiency during pregnancy.

3-Diol-G levels
Androgen status was evaluated by 3-Diol-G levels in
158 females with Addisons disease and 114 blood donors
(Fig. 1). Addisons patients (n 122) not taking DHEA
and not reporting premature ovarian insufficiency had sig-
nificantly lower 3-Diol-G than blood donors (mean, FIG. 1. 3-Diol-G measurements in nanograms per milliliter (y-axis)
in the following patient categories (x-axis): A (Addisons patients),
0.53 vs. 2.2 ng/ml; P 0.0001; Mann-Whitney U test).
n 122; BD (blood donors), n 114; DHEA (Addisons patients
The 3-Diol-G levels did not correlate significantly with taking DHEA), n 13; and PM (Addisons patients with a history of
age (data not shown). Patients taking DHEA (n 13) had premature ovarian insufficiency), n 21.

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4358 Erichsen et al. Female Sexuality and Fertility in Addisons Disease J Clin Endocrinol Metab, September 2010, 95(9):4354 4360

ues of 3-Diol-G than Addisons women without such a our data argue against reduced sexual activity in these
history (mean, 0.36 vs. 0.53 ng/ml; P 0.0001; Mann- women. The explanation may be complex, but perhaps
Whitney U test). response shift, namely a change in values and elements of
quality of life, is a main factor involving many aspects of
womens lives (28). In patients with Addisons disease, the
Discussion treatment with glucocorticoids has potential psychophar-
macological effects because they are presumed to be over-
In this study, we demonstrate for the first time that, despite
replaced in many patients (3). Although the conventional
subnormal levels of androgens, females with Addisons
replacement doses are not expected to elicit serious mental
disease do not report reduced sexual activity compared
side effects like those that are common in pharmacological
with controls from the general population. However, after
glucocorticoid therapy, mild euphoria or well-being asso-
the diagnosis of Addisons disease was made, these women
ciated with slight overreplacement possibly alter sexual
had significantly fewer childbirths than expected.
behavior and contribute to the positive SAQ scores re-
The adrenals are major sources of androgens in women,
corded here.
but there is a significant contribution from the ovaries,
Our results thus challenge the notion that androgens
which is normally maintained after menopause (26). Thus,
are important for sexual functioning in women (29). The
Addisons disease women lack androgen precursors from
Endocrine Society does not recommend making a diagno-
the adrenals, whereas the subgroup with concomitant au-
sis of androgen deficiency in women because of the lack of
toimmune ovarian failure has more severe androgen de-
a well-defined clinical syndrome (30). Davis et al. (31)
pletion. Although low levels of circulating androgens have
been demonstrated in women with Addisons disease, we recently reported that no single androgen level was pre-
verify that the cellular levels as indicated by the androgen dictive of poor sexual function in a large community-
metabolite 3-Diol-G levels are significantly reduced; this based study. An interesting control group is women with
is even more significant in the subgroup of patients with the rare syndrome of complete androgen insensitivity.
premature ovarian insufficiency. The patients on DHEA Studies on their psychosexual adjustment showed no dif-
treatment had high levels of 3-Diol-G. There is a delicate ferences from that of control women (32, 33), except prob-
balance between unacceptable side effects like androgen- lems related to surgical reconstruction (34). Nevertheless,
induced odorous apocrine sweating, changed hair growth a possible effect on libido has attracted interest through
pattern, voice influence, and acne and the well-being and many intervention studies with DHEA. Some studies have
energy that this substance possibly provides. Labrie et al. shown that healthy women benefit from DHEA therapy
(27) have pointed out that the therapeutic dose of DHEA (3537), whereas older studies refute this (11, 12). In Ad-
depends on the transformation to active hormones, show- disons disease only, Arlt et al. (4) found a positive effect
ing a mismatch between DHEA levels and 3-Diol-G; the of DHEA on sexual function. However, the study was
efficacy of further transformation of DHEA to active hor- small and had cross-over design, which implies a risk for
mones was only 35% during DHEA replacement, com- lack of blinding. Later, a number of studies have failed to
pared with the transformation of DHEA under basal con- verify improved sexuality in response to DHEA treatment
ditions. This supports the use of 3-Diol-G measurement (2, 5, 13, 14).
in the assessment of the DHEA replacement therapy. Our data do not explain the reduction in childbirths; we
The SAQ is a valid and psychometrically tested instru- show that in the fertile years there were significantly fewer
ment to show differences in female sexual activity. The than expected children born to Addisons disease women,
Norwegian normative study (n 1165) is the largest so far whereas in the fertile years before the diagnosis was made,
using the SAQ (18). Interestingly, the Addisons disease the number of births was in the normal range. The loss of
females reported significantly higher sexual pleasure and adrenal androgens could possibly influence the fertility,
lower discomfort during intercourse than the normative but this has not been studied. Increase in spontaneous
control women. These patients also reported significantly abortions has been associated with Addisons disease pre-
more sexual activity than the controls, but the ES did not senting in pregnancy, whereas the prognosis of pregnan-
indicate clinical significance (25). The explanation why cies in patients with known Addisons disease has usually
the Addisons disease females and the RRSO females re- been considered good (38). Furthermore, concomitant
ported less discomfort than females from the general diseases such as autoimmune thyroid disease and prema-
population may, however, not depend only on hor- ture ovarian insufficiency are possible causes of reduced
monal differences. Obviously, satisfaction is relative to fertility in these patients, as well as inappropriate treat-
expectations, and one might suspect that the sexual drive ment of adrenal insufficiency. The burden of disease, with
be reduced in females with Addisons disease. However, loss of the energy and the vitality required for wanting and

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J Clin Endocrinol Metab, September 2010, 95(9):4354 4360 jcem.endojournals.org 4359

planning a pregnancy and to rear children (1, 39), is a term DHEA replacement in primary adrenal insufficiency: a ran-
domized, controlled trial. J Clin Endocrinol Metab 93:400 409
likely reason for fewer births in Addisons disease women.
3. Erichsen MM, Lvs K, Skinningsrud B, Wolff AB, Undlien DE,
Whether some women feared Addisons disease as an in- Svartberg J, Fougner KJ, Berg TJ, Bollerslev J, Mella B, Carlson JA,
heritable disease in relation to family planning was not Erlich H, Husebye ES 2009 Clinical, immunological, and genetic
explored. Thus, whether reduced birth rates represents features of autoimmune primary adrenal insufficiency: observations
from a Norwegian registry. J Clin Endocrinol Metab 94:4882 4890
social or psychological adaptation to the disease, altered 4. Arlt W, Callies F, van Vlijmen JC, Koehler I, Reincke M, Bidling-
sexual interest and activity, or truly reduced fertility is not maier M, Huebler D, Oettel M, Ernst M, Schulte HM, Allolio B 1999
certain. Dehydroepiandrosterone replacement in women with adrenal in-
sufficiency. N Engl J Med 341:10131020
Some limitations apply to the interpretation of our
5. Hunt PJ, Gurnell EM, Huppert FA, Richards C, Prevost AT, Wass
data. The response rate in the normative group was lower JA, Herbert J, Chatterjee VK 2000 Improvement in mood and fa-
(42%) than that in the Addisons disease group (65%). In tigue after dehydroepiandrosterone replacement in Addisons dis-
questionnaire studies of sexuality in Scandinavia, the re- ease in a randomized, double blind trial. J Clin Endocrinol Metab
85:4650 4656
sponse rates rarely exceed 50% (40). The positive SAQ 6. Lvs K, Gebre-Medhin G, Trovik TS, Fougner KJ, Uhlving S,
scores could possibly represent selection bias, if patients Nedreb BG, Myking OL, Kampe O, Husebye ES 2003 Replace-
with impaired sexual interest systematically refrained ment of dehydroepiandrosterone in adrenal failure: no benefit for
subjective health status and sexuality in a 9-month, randomized,
from responding to the questionnaire. However, response parallel group clinical trial. J Clin Endocrinol Metab 88:11121118
bias has been shown not to be a major problem in former 7. Taieb J, Mathian B, Millot F, Patricot MC, Mathieu E, Queyrel N,
studies because nonresponders were randomly distributed Lacroix I, Somma-Delpero C, Boudou P 2003 Testosterone mea-
sured by 10 immunoassays and by isotope-dilution gas chromatog-
(41), supporting a representative distribution from the
raphy-mass spectrometry in sera from 116 men, women, and chil-
participants. Norwegian women are quite homogeneous dren. Clin Chem 49:13811395
when it comes to culture, religion, and ethnicity. However, 8. Labrie F, Belanger A, Belanger P, Berube R, Martel C, Cusan L,
educational and geographical level was not adjusted for Gomez J, Candas B, Castiel I, Chaussade V, Deloche C, Leclaire J
2006 Androgen glucuronides, instead of testosterone, as the new
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depletion, female patients with Addisons disease on a 9. Shifren JL, Braunstein GD, Simon JA, Casson PR, Buster JE,
Redmond GP, Burki RE, Ginsburg ES, Rosen RC, Leiblum SR,
group level do not report impaired sexuality. The birth Caramelli KE, Mazer NA 2000 Transdermal testosterone treatment
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Vignali M 2001 Effects of androgen supplementation of hormone
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Acknowledgments Fertil Steril 76:235240
11. Morales AJ, Nolan JJ, Nelson JC, Yen SS 1994 Effects of replace-
We thank Inger J. Nss for handling the SAQ forms and Elisa- ment dose of dehydroepiandrosterone in men and women of ad-
vancing age. J Clin Endocrinol Metab 78:1360 1367
beth T. Halvorsen for analyzing the 3-Diol-G in all our partic-
12. Barnhart KT, Freeman E, Grisso JA, Rader DJ, Sammel M, Kapoor
ipants and in the blood donors. We also thank the Addisons S, Nestler JE 1999 The effect of dehydroepiandrosterone supple-
disease women who participated in this study. mentation to symptomatic perimenopausal women on serum endo-
crine profiles, lipid parameters, and health-related quality of life.
Address all correspondence and requests for reprints to: Martina J Clin Endocrinol Metab 84:3896 3902
Moter Erichsen, M.D., Section for Endocrinology, Department of 13. Lvs K, Husebye ES 2003 Replacement therapy in Addisons dis-
Medicine, Haukeland University Hospital, N-5021 Bergen. E-mail: ease. Expert Opin Pharmacother 4:21452149
mmer@helse-bergen.no. 14. van Thiel SW, Romijn JA, Pereira AM, Biermasz NR, Roelfsema F,
van Hemert A, Ballieux B, Smit JW 2005 Effects of dehydroepi-
This research is funded by European Union Seventh Frame-
androstenedione, superimposed on growth hormone substitution,
work Programme Grant 201167, Euradrenal, and supported by on quality of life and insulin-like growth factor I in patients with
grants from the Regional Health Authorities of Western Nor- secondary adrenal insufficiency: a randomized, placebo-controlled,
way. M.M.E. is a doctoral fellow of the Regional Health Au- cross-over trial. J Clin Endocrinol Metab 90:32953303
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Disclosure Summary: The authors have nothing to disclose. D, Sherman JC, Swearingen B, Loeffler J, Klibanski A 2006 Effects
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