The n e w e ng l a n d j o u r na l of m e dic i n e
c or r e sp ondence
Testosterone for Low Libido
To the Editor: Neither serum levels of testoster-
one nor total androgen activity as assessed by mea-
surement of androgen metabolites has been shown
to correlate with women’s sexual function.1,2 Given
the reduction in testosterone production with age
— most notably, the intracrine production from
adrenal precursors3 — it is reasonable to hypoth-
esize that some middle-aged and older women
might have sexual dysfunction due to insufficient
testosterone. The difficulty with the trial reported
by Davis et al. (Nov. 6 issue)4 and previous trials is
that at baseline, the recruited women reported that
approximately 50% of their sexual experiences were
satisfying, with an average of two to three satisfy-
ing experiences per month. There remains debate
about whether this constitutes sexual disorder.1
Moreover, nonmedical factors are surely at play in
these nonrewarding experiences: biologic factors
(e.g., a testosterone deficit) would cause consistent
dysfunction. There is a need for studies that re-
cruit women who have no satisfying sexual expe-
riences: their former means of stimulating mind
and body is no longer effective.1,5 Such women with
sexual disorder according to recommended crite-
ria have yet to be enrolled in randomized trials of
testosterone supplementation.
this week’s letters
728 Testosterone for Low Libido
729 Gastroesophageal Reflux Disease
730 Varenicline for Tobacco Dependence
731 A Family with Complete Resistance
to Thyrotropin-Releasing Hormone
734 An Unusual Outbreak of Hypoglycemia
728 n engl j med 360;7  nejm.org  february 12, 2009
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Rosemary Basson, M.D.
University of British Columbia
Vancouver, BC V5Z 1M9, Canada
bassonrees@telus.net
1. Basson R. Sexual desire and arousal disorders in women.
N Engl J Med 2006;354:1497-506.
2. Adler J, Zanetti R, Wight E, Urech C, Fink N, Bitzer J. Sexual
dysfunction after premenopausal stage I and II breast cancer: do
androgens play a role? J Sex Med 2008;5:1898-906.
3. Labrie F, Bélanger A, Bélanger P, et al. Androgen glucuronides,
instead of testosterone, as the new markers of androgenic activ-
ity in women. J Steroid Biochem Mol Biol 2006;99:182-8.
4. Davis SR, Moreau M, Kroll R, et al. Testosterone for low li-
bido in postmenopausal women not taking estrogen. N Engl J
Med 2008;359:2005-17.
5. Basson R, Leiblum S, Brotto L, et al. Revised definitions of
women’s sexual dysfunction. J Sex Med 2004;1:40-8.
The authors reply: The aim of our study was to
investigate the efficacy of transdermal testoster-
one therapy over a 6-month period and its safety
over a 12-month period in women who met the
criteria for hypoactive sexual desire disorder.1 Par-
ticipants in the study had a range of frequencies
of satisfying sexual events at baseline and includ-
ed women who reported no satisfying events. Over-
all, the baseline data showed that the participants
had a low frequency of satisfying sexual activi-
ties, that they seldom had sexual desire, and that
they were all distressed by their loss of interest in
sexual activity. Whether individual women expe-
rienced their former means of stimulating mind
and body as no longer effective on all or only some
occasions may not be a meaningful way of differ-
entiating the severity of the condition from the
individual woman’s perspective. Rather, it may re-
flect sexual experience and knowledge and vary-
ing degrees of effort made by either the woman
or her partner to enhance the sexual experience.
The critical issue in describing this study popula-
tion is that the participants felt that their loss of
 correspondence

sexual desire was sufficiently severe that they Cindy Rodenberg, Ph.D.
wished to try a treatment to improve their sexual Procter & Gamble Pharmaceuticals
Mason, OH 45040
interest and sexual experience.
1. Diagnostic and statistical manual of mental disorders, 4th
Susan R. Davis, M.D., Ph.D.
ed.: DSM-IV. Washington, DC: American Psychiatric Associa-
Monash University tion, 1994.
Prahran, VIC 3181, Australia
susan.davis@med.monash.edu.au

Gastroesophageal Reflux Disease

To the Editor: In his article about gastroesoph-
ageal reflux disease, Kahrilas (Oct. 16 issue)1 de-
scribes the potential risks of prolonged use of pro-
ton-pump inhibitors. However, the author does not
call attention to the important relation between
sustained hypochlorhydria and vitamin B12 and
iron deficiency.
Vitamin B12 deficiency is a major public health
problem in the elderly population. Long-standing
administration of proton-pump inhibitors can re-
sult in malabsorption of cobalamin in food2 and
contribute, along with conditions such as auto-
immune gastritis and lifestyle choices such as
vegetarianism, to the development of clinically
manifest vitamin B12 deficiency.3 Moreover, it is
well known that hypochlorhydria secondary to
early or full-blown autoimmune atrophic gastritis
is one of the main causes of refractory iron-defi-
ciency anemias in the absence of chronic gastro-
intestinal bleeding.4 The causal mechanism is
closely related to the persistently low production
of hydrochloric acid.5 Hypochlorhydria caused by
treatment with proton-pump inhibitors could have
similar consequences. Therefore, in patients treat-
ed over the long term with proton-pump inhibi-
tors, close clinical vigilance is warranted for the
early detection and correction of vitamin B12 and
iron deficiency.
Ciriaco Aguirre, M.D., Ph.D.
Guillermo Ruiz-Irastorza, M.D., Ph.D.
University of the Basque Country
48903 Barakaldo, Spain
r.irastorza@euskalnet.net
Maria-Victoria Egurbide, M.D., Ph.D.
Hospital de Cruces
48903 Barakaldo, Spain
1. Kahrilas PJ. Gastroesophageal reflux disease. N Engl J Med
2008;359:1700-7.
2. Carmel R. Current concepts in cobalamin deficiency. Annu
Rev Med 2000;51:357-75.
3. Andrès E, Noel E, Abdelghani MB. Vitamin B(12) deficiency
associated with chronic acid suppression therapy. Ann Pharma-
cother 2003;37:1730.
4. Hershko C, Hoffbrand AV, Keret D, et al. Role of autoim-
mune gastritis, Helicobacter pylori and celiac disease in refractory
or unexplained iron deficiency anemia. Haematologica 2005;90:
585-95.
5. Annibale B, Capurso G, Delle Fave G. The stomach and iron
deficiency anaemia: a forgotten link. Dig Liver Dis 2003;35:288-
95.
To the Editor: As Kahrilas notes, maintenance
acid-suppressing therapy is often necessary in pa-
tients with gastroesophageal reflux disease. A trou-
blesome issue regarding indefinite treatment with
proton-pump inhibitors is the propensity for chron-
ic atrophic gastritis to develop in patients infected
with Helicobacter pylori.1 Atrophic gastritis could
theoretically lead to an increased risk of gastric
cancer. On the other hand, some studies have
shown that eradication of H. pylori in patients with
reflux esophagitis who are receiving proton-pump
inhibitors can decrease inflammation and reverse
corpus gastritis.2 As a result, the current guide-
lines of the European Helicobacter Study Group
suggest that H. pylori testing be considered in pa-
tients receiving long-term maintenance treatment
with proton-pump inhibitors.3
Francisco José Fernández-Fernández, M.D.
Hospital Arquitecto Marcide
15405 Ferrol, Spain
fjf-fernandez@terra.es
1. Kuipers EJ, Lundell L, Klinkenberg-Knol EC, et al. Atrophic
gastritis and Helicobacter pylori infection in patients with reflux
esophagitis treated with omeprazole or fundoplication. N Engl J
Med 1996;334:1018-22.
2. Kuipers EJ. Proton pump inhibitors and gastric neoplasia. Gut
2006;55:1217-21.
3. Malfertheiner P, Megraud F, O’Morain C, et al. Current con-
cepts in the management of Helicobacter pylori infection: the
Maastricht III Consensus Report. Gut 2007;56:772-81.
The author replies: Proton-pump inhibitors are
highly efficacious in maintaining remission in pa-
tients with gastroesophageal reflux disease or pep-

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