ARTICLE IN PRESS

Voice Change Following Testosterone Supplementation

in Women: A Multi-Institutional Case Series
*Keith A. Chadwick, †C. Blake Simpson, †Patrick O. McGarey Jr., *Christine Murphy Estes, ‡John Nix, and
*Lucian Sulica, *New York, New York, and yzSan Antonio, Texas

Summary: Objectives. To describe voice changes as a result of the off-label use of androgen supplementation
in women.
Methods. A multi-institutional retrospective consecutive case series identified women taking androgen supple-
mentation who presented to voice clinics at two institutions with a chief complaint of voice change between 2014
and 2019. Age, occupation, hormone therapy, indication, Voice Handicap Index-10, fundamental frequency,
semitone pitch range, testosterone blood level, treatment undertaken, and long-term outcome were collected.
Results. Nine women presented with voice change after initiation of androgen hormone supplementation. The
mean age was 55 and three patients were performers. All patients underwent hormone therapy with testosterone
supplementation, most commonly subcutaneous testosterone pellets. Six patients (67%) were being treated for
menopause symptoms, one patient for decreased libido, one patient for breast cancer, and one patient who
desired additional muscle gain. Time of symptom onset after hormone therapy initiation was highly variable,
ranging from 0 to 48 months with a mean of 15 months. Mean Voice Handicap Index-10 was 21, mean funda-
mental frequency at comfortable speaking level was 155 Hz and mean semitone pitch range was 22 semitones.
Two patients had markedly elevated serum total testosterone levels. Hormone therapy discontinuation and voice
therapy were recommended in six (67%) patients each. Five patients returned for follow-up after treatment and
noted some subjective benefit.
Conclusions. Female patients treated with androgen supplementation may experience unintended voice
changes, most prominently reduction in fundamental frequency. Although some benefit may be obtained from
voice therapy and cessation of hormone therapy, voice changes may be permanent. Caution should be exercised
when prescribing these medications to women.
Key Words: Hormone replacement therapy−Testosterone−Androgen−Menopause−Voice change−Dysphonia.

INTRODUCTION voice change, or actively state that it does not occur. In one
Hormonal supplementation therapy with androgens, includ- review, it is stated as “fact” that “there is no conclusive evi-
ing anabolic steroids and other testosterone derivatives, has dence that testosterone therapy causes hoarseness or irre-
been used in women for breast cancer, endometriosis, osteo- versible vocal cord changes in women.” 4 The objectives of
porosis, and for muscle gain. More recently, androgen hor- this study are to describe cases of voice change in women
monal supplementation has been advocated as safe and taking androgen supplementation and to record baseline
effective treatment for menopausal symptoms (hot flashes, characteristics and response to therapy.
sleep problems, irritability, and fatigue) and decreased
libido.1-3 Since these medications are not approved for these
indications by the United States Food and Drug Adminis- MATERIALS AND METHODS
tration, treatment is off-label. However, these treatments After obtaining institutional review board ethics committee
may have negative and unintended consequences on the approval at both participating sites, a multi-institutional ret-
voice because of hormonal effects on the larynx. rospective consecutive case review was performed. Female
Existing reviews of androgen hormone therapy used off- patients taking androgen supplementation who presented to
label for menopause and libido minimize this potential for voice clinics at two institutions (Sean Parker Institute for
the Voice at Weill Cornell Medicine and the Voice Center
Accepted for publication March 24, 2020.
at University of Texas Health San Antonio) with a chief
Presented at The Fall Voice Conference, Plano, TX, USA, October 17, 2019. complaint of voice change between September 2014 and
Funding: None.
Conflicts of Interest: None.
May 2019 were identified. Each patient underwent a com-
From the *Sean Parker Institute for the Voice, Department of Otolaryngology - prehensive evaluation by a laryngologist including videolar-
Head & Neck Surgery, Weill Cornell Medical College, New York, New York; yThe
University of Texas Health Science Center, Department of Otolaryngology, San
yngostroboscopy. Demographic and baseline information
Antonio, Texas; and the zThe University of Texas at San Antonio, Department of of each patient was collected, including age at presentation
Music, San Antonio, Texas.
Address correspondence and reprint requests to Keith A. Chadwick, Sean Parker
(in years), occupation/vocal demand, hormone therapy
Institute for the Voice, Department of Otolaryngology - Head & Neck Surgery, Weill used, indication for treatment, testosterone blood level
Cornell Medical College, 240 East 59th Street, New York, NY 10022.
E-mail: [email protected]
(when available), time of symptom onset, and tobacco use
Journal of Voice, Vol. &&, No. &&, pp. &&−&& history. Voice data for each patient included Voice Handi-
0892-1997
© 2020 The Voice Foundation. Published by Elsevier Inc. All rights reserved.
cap Index-10, fundamental frequency, and semitone pitch
https://doi.org/10.1016/j.jvoice.2020.03.008 range. Acoustic measures were taken using Computerized
 ARTICLE IN PRESS
2 Journal of Voice, Vol. &&, No. &&, 2020

Speech Lab (PENTAX Medical, Montvale, NJ). Funda- initiation was highly variable, ranging from 0 to 48 months
mental frequency was defined as the patient’s average com- with a mean of 15 months. One patient (patient 7) reported
fortable speaking pitch in connected speech. Recommended exacerbation of existing dysphonia immediately after hor-
treatments and long-term results were also collected. Dei- mone treatment. Two patients (patients 2 and 4) underwent
dentified data were pooled between treatment sites and testing for serum testosterone levels, and both patients had
reported in aggregate. Descriptive statistics are used to markedly elevated total testosterone levels: 169.0 ng/dL and
report results. 178.2 ng/dL, respectively. The normal reference range for
adult women is 10-60 ng/dL.5 No patients were actively
smoking at the time of symptom onset. Four patients (50%)
RESULTS had prior tobacco use history; however in all patients the
Nine women presented with voice changes after initiation of most recent tobacco use was over 10 years prior and cumu-
androgen hormone supplementation. Most patients lative tobacco use was less than 5 pack-years.
reported symptoms of decreased pitch but other complaints In all nine patients, alternative laryngeal diagnoses were
included roughness, decreased stamina, pitch breaks, and ruled out by videolaryngostroboscopy. A representative still
inability to access the upper register. The characteristics of image from a laryngeal examination (patient 4) is shown in
these patients are summarized in Table 1. Five patients were Figure 1; video is available online. Stroboscopic findings for
seen at the Sean Parker Institute for the Voice at Weill Cor- each patient are described in Table 2; all patients had evi-
nell Medicine and four patients were seen at the Voice Cen- dence of increased mucosal wave amplitude and normal
ter at University of Texas Health San Antonio. The mean supraglottic activity. Baseline voice characteristics for each
age was 55 years (range 44-66 years). Three patients had patient are reported in Table 3. Mean Voice Handicap
routine vocal demands, two patients had high vocal Index-10 at presentation was 21 (range 8-31), mean funda-
demands associated with their occupation, and three mental frequency at comfortable speaking level was 155 Hz
patients were performers. All patients had undergone hor- (range 117-190 Hz), and mean semitone pitch range was 22
mone therapy with testosterone supplementation of varying semitones (range 12-40 semitones).
dosages and administration routes, most commonly subcu- Recommended treatment is summarized in Table 4. Hor-
taneous testosterone pellets (TESTOPEL; six patients). Six mone therapy discontinuation and voice therapy were rec-
patients (67%) were treated for menopause symptoms, one ommended in six (67%) patients each. A trial of
patient for decreased libido, and one patient for breast can- corticosteroids was recommended in one patient (patient 7)
cer (treated with estrogen-receptor blocker 6 years prior). without significant improvement, and she was referred for
One patient underwent treatment with a single dose of intra- voice therapy. Three patients (patients 1, 5, and 6) who
muscular testosterone for muscle gain. In three of the were recommended voice therapy and hormone discontinu-
patients treated for menopause (patients 2, 3, and 5), meno- ation reported some subjective improvement but not a
pause had started at least 3 years prior to treatment with tes- return to baseline. Patient 5 discontinued testosterone
tosterone. Time of symptom onset after hormone therapy implantation and noted a slight improvement in subjective

TABLE 1.
Participant Characteristics
Patient Center Age Occupation Vocal Hormone Indication for Symptom Onset
(Yrs) Demands Replacement HRT (Months After
Therapy (HRT) Initiation of HRT)
1 1 66 Realtor High Testosterone Breast cancer 48
topical
2 1 58 Housewife Routine Testosterone SQ Menopause 36
3 1 57 Realtor High Testosterone SQ Menopause 0
4 1 44 Teacher High Testosterone IM Muscle gain 0
(single dose)
5 1 55 Interior designer Routine Testosterone SQ Menopause 24
6 2 44 Insurance/Avoca- Performer Testosterone SQ Menopause 3
tional vocalist
7 2 59 Vocal coach Performer Testosterone SQ Menopause
8 2 44 Professional vocalist Performer Testosterone SQ Decreased 6
libido
9 2 65 Housewife Routine Testosterone SQ Menopause 3
Mean: Mean: 15
55 yrs months
Yrs, years.
 ARTICLE IN PRESS
Keith A. Chadwick, et al Testosterone Voice Change 3

FIGURE 1. a and b. Still image from videostroboscopic examination of patient 4. In both modal (a) and high-pitched (b) phonation, the
vocal folds appear slightly thickened, edematous, and with a mild tan discoloration. These findings are consistent with thickening of the
superficial lamina propria as a result of the laryngeal effects of testosterone. Video is available online.

TABLE 2.
Baseline Laryngovideostroboscopic Findings
Pt. Closure Amplitude Supraglottic Activity Phase Symmetry Regularity Edema Hypervascularity
1 Complete Increased Normal Symmetric 100% + -
2 Posterior gap Increased Normal Symmetric 70% + +
3 Complete Increased Normal Symmetric 90% + +
4 Spindle gap Increased Normal Asymmetric 80% + +
5 Posterior gap Increased Normal Symmetric 80% + +
6 Incomplete Increased Normal Asymmetric 100% + +
7 Hourglass Increased Normal Symmetric 100% + +
8 Posterior gap Increased Normal Asymmetric 90% + +
9 Complete Increased Normal Symmetric 100% + +
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4 Journal of Voice, Vol. &&, No. &&, 2020

TABLE 3.
Baseline Voice Characteristics
Patient VHI-10 F0 (Hz) Frequency Range (Hz) Frequency Range (Semitones)
1 31 117 97 to 274 18
2 8 130 105 to 315 19
3 23 190 174 to 347 12
4 25 170 131 to 306 15
5 24 118 106 to 265 16
6 23 168 168 to 387 14
7 17 172 96 to 974 40
8 27 177 169 to 1081 32
9 12 156 83 to 409 28
Mean: 21.11 Mean: 155.33 Hz Mean: 21.5 semitones
Hz, hertz; VHI-10, Voice Handicap Index-10.

TABLE 4.
Treatment and Treatment Outcomes
Patient Treatments Recommended Subjective Outcome
Voice Therapy HRT Discontinuation Other
1 X X + improvement
2 X X Lost to follow-up
3 X X Lost to follow-up
4 + improvement
5 X + improvement
6 X X Singing therapy + improvement
7 X Oral steroids No improvement after oral
steroids, lost to follow-up
8 X Singing therapy Lost to follow-up
9 X Lost to follow-up

voice quality at follow-up. Patient 4, who had received a sin- Despite these well-documented hormonal effects, prior
gle dose of intramuscular testosterone for muscle gain, was studies on testosterone supplementation for the off-label
not recommended any treatment but noted some improve- indications of menopause symptoms and decreased libido
ment with time. Her serum testosterone level was followed have failed to demonstrate any meaningful voice changes,
over several months until it returned to normal range. The leading authors to conclude that this treatment does not
remainder of patients were lost to follow-up. have a voice effect. However, the literature is inadequate to
support this conclusion. A systematic review and meta-anal-
ysis evaluating the safety of transdermal testosterone
DISCUSSION patches (ANDRODERM) for women with hypoactive sex-
The virilizing effects of exogenous androgens are well- ual desire disorder found that there was no statistically
documented. Significant deepening of the voice occurs increased risk of “voice deepening” (RR 1.12, 95% CI [0.64,
when high doses of androgens are used, such as with ana- 1.67]).18 Five individual studies are cited as evidence; how-
bolic steroids6-9 and hormone therapy for transgender ever, each of these studies is designed to evaluate treatment
men.10-13 Subjective decrease in spoken voice pitch has efficacy as the primary outcome, and safety and tolerability
also been seen in women treated with testosterone, whether were secondary outcomes based solely on patient self-
injected or implanted,9 oral14 or topical.15 This effect report. Since the studies were not designed to detect a poten-
appears to be both dose-dependent16 and time-dependent.17 tial difference in voice outcomes, a type II error may have
In the present study, we identified eight patients who had occurred.
voice changes consistent with the virilizing effects of andro- To date there have been two studies specifically designed
gen therapy that were temporally related to testosterone to evaluate the effects of testosterone supplementation on
supplementation. None of these patients were made aware voice in women. Huang et al measured fundamental fre-
or counseled about the potential for voice change by the quency before and after treatment in 71 posthysterectomy
treating provider. (postmenopausal) women undergoing weekly intramuscular
 ARTICLE IN PRESS
Keith A. Chadwick, et al Testosterone Voice Change 5

injections of testosterone at different dosages.16 Patients have shown positive effects when the mean serum total tes-
who underwent treatment with a higher dose of testosterone tosterone increased from 17 ng/dL to 66 ng/dL24 and from
had a dose- and serum concentration-dependent lowering of 21 ng/dL to 68 ng/dL.25 However in a series of studies from
fundamental frequency. In contrast, Glaser et al found no one group evaluating treatment with weight-based dosing of
significant differences in fundamental frequency of 10 subcutaneous testosterone pellets, efficacy was only seen
patients who underwent testosterone therapy with a subcu- when serum total testosterone levels were increased to 4-
taneous implant using weight-based dosing for 1 year.19 6 times the upper range of normal,26 and from a baseline of
However, this study was limited by a small sample size and 17.2 ng/dL to 471.6 ng/dL on treatment.19 The Huang study
diverse patient characteristics (menopause status and active demonstrating a dose-dependent decrease in fundamental
tobacco use) which may have confounded the results. The frequency found that serum total testosterone levels
authors cited two studies evaluating the voice effects of increased to as high as 250 ng/dL depending on the dose of
treatment with danazol, a testosterone derivative, to rebut treatment.16 Given this wide variation in post-treatment
the claim that androgen supplements lead to voice changes, serum total testosterone levels, additional study is needed to
though both also had small sample sizes (23 patients20 and determine target values for serum testosterone that have
10 patients21). Contradictory results were noted in a review maximum efficacy and lowest risk of adverse voice effects.
of 400 women with dysphonia seen over a 4-year period; A study of transgender men undergoing cross-sex hormone
about 40 (~10%) patients had symptoms attributed to viril- therapy found that patients’ total testosterone levels
izing agents.6 Thus, any statement that virilizing agents can- increased from 61 ng/dL to 720 ng/dL with hormone treat-
not cause a voice change is unfounded. ment,11 and the significant decrease in fundamental fre-
Despite a dose-dependent decrease of fundamental fre- quency in this population has been well-documented.11,27-29
quency, none of the patients in the Huang study described a In our cohort, patients tested were found to have elevated
voice complaint after treatment,16 although none were pro- levels of testosterone. Although one of our patients was
fessional vocalists or singers and may not have been sensi- treated with weight-based subcutaneous implanted testos-
tive to mild alterations in vocal mechanics. terone pellets, she had a markedly elevated serum testoster-
Some voice complaints associated with virilization, such one level, indicating that potentially supratherapeutic levels
as pitch breaks and difficulty reaching the upper register, can occur even with seemingly appropriate dosing. There-
may be less noticeable to patients with routine voice fore, care should be taken when prescribing these medica-
demands. Therefore, relying on subjective patient report tions and serum testosterone level monitoring may be
alone may be inadequate to detect a voice change after tes- necessary to prevent overtreatment.
tosterone supplementation. The incidence of voice change in the population treated
Alterations in validated objective acoustic measures, such with androgens is difficult to establish. In two busy aca-
as fundamental frequency, are less subjective. In the current demic laryngology practices, only eight patients were identi-
study, all identified patients had a decreased fundamental fied in a 4-year period who had dysphonia attributed to
frequency when compared with age-matched female norma- androgen use. However, patients are not routinely ques-
tive values (195 § 3.4 Hz for ages 40-55), with some patients tioned about their use of hormonal supplementation and
having a fundamental frequency much closer to male nor- are unlikely to volunteer information regarding treatment
mative values (100 § 2.6 Hz for ages 40-55).22 In addition, for libido and other perceived “unusual” indications. Addi-
most patients had significantly reduced pitch range com- tionally, many patients do not consider hormone supple-
pared to normative values for age-matched women (30.75 mentation to be a “medication” and fail to report its use the
semitones for ages 35-70).22 treating physician. It is likely that not all patients with
Voice complaints may occur immediately after initiation potential androgen-mediated voice change are identified. In
of treatment, or more gradually with sustained treatment. the meta-analysis by Achilli et al, voice effects were seen in
In the current study, symptoms started (or worsened) imme- 3.0% to 7.9% of those receiving testosterone supplementa-
diately after hormone therapy initiation in three patients tion and were overall similar to rates among subjects who
(patients 4, 5, and 7) and after 3 months in two patients received placebo.18 In one study, twice as many patients
(patients 6 and 9). Other patients had onset of symptoms reported voice deepening with testosterone supplementation
months or years after the onset of testosterone therapy sug- than with placebo; however the difference was not statisti-
gesting that long-term treatment could have a gradual, cally significant and it was rare in both treatment arms
cumulative effect. In the Achilli meta-analysis, patients in (1.5% versus 3.0%).30 Studies by Shifren and Simon also
each study are followed for less than 6 months, which may reported low rates of “voice deepening” with testosterone
be inadequate to fully evaluate voice effects.18 treatment similar to placebo (around 3% in both placebo
Markedly supratherapeutic levels of serum testosterone and treatment groups).24,31
can have a virilizing effect, and it has been suggested that Another study questioned patients simply about “voice
these changes may be irreversible in the larynx.23 There are changes” rather than deepening and found a similarly low
currently no therapeutic guidelines for target levels of serum rate of self-reported changes (2.8% for placebo, 3.8% for
total testosterone when using testosterone supplementation treatment arm) that were not significantly different between
for decreased libido or menopause. Several efficacy studies groups.25 A study evaluating treatment with two dosages of
 ARTICLE IN PRESS
6 Journal of Voice, Vol. &&, No. &&, 2020

a testosterone transdermal patch (150 mg and 300 mg) or that there is a link between the hormonal environment and
placebo32 showed a higher rate of “voice deepening” than vocal dynamics. However further study is needed to separate
other studies, but this was similar across all treatment arms potential confounders, such as menopausal status. Also, there
(7.2% for placebo, and 7.1% and 7.9% for treatment arms). is no control group and limited follow-up data since the pre-
It is unclear why the rate of voice changes in this study is sented study is a retrospective case series, and acoustic meas-
much higher than in other cited studies, especially since ures were not obtained prior to androgen supplementation.
patient self-report is used in each. In this study, we compared patients’ acoustic measures with
Discontinuation or reduction of the hormone dose is established normative values for age; however future research
obviously essential in treatment of patients with a voice efforts should consist of voice evaluation before and after
change after hormone therapy. Hormone supplementation treatment in both treated patients and age-matched con-
should be discontinued when medically safe so that any fur- trols. It would also be beneficial to obtain acoustic measure-
ther virilizing effects will be mitigated. ments that may correlate objectively with roughness,
The role of voice therapy is undetermined. Specific facili- including harmonics-to-noise ratio, cepstral peak promi-
tation techniques to consider include semioccluded vocal nence, or cepstral index of dysphonia, which were not avail-
tract postures (SOVTs), pitch glides, resonance/tonal focus able in the majority of cases. Finally, this appears to be a
exercises, sighing/sliding patterns, phonatory airflow techni- relatively uncommon risk of hormone supplementation
ques, and pitch agility patterns. SOVTs (eg, straw phona- which makes it difficult to study and establish causality.
tion, bilabial fricatives, lip trills, and humming) and pitch Future studies should include a large number of patients
glides may help patients balance register transitions more providing adequate power to definitively determine the
efficiently. SOVTs can also be used as lead-ins for individual voice effects of testosterone supplementation.
vowels, vocalization patterns, or phrases in order to general-
ize these techniques to functional vocal tasks. Maneuvers
focused on resonance and tonal focus may be used to estab- CONCLUSIONS
lish a “brighter” voice quality and reduce “darkening” of Women treated with androgen supplementation may experi-
vocal timbre with hormone therapy. Such techniques have ence unintended voice changes, most prominently a reduction
been helpful in increasing pitch and perceived femininity in in fundamental frequency. Although some improvement may
transfeminine individuals,33,34 although have not been spe- result from cessation of hormone therapy, voice changes can
cifically studied in cisgender females who receive androgen be permanent. The role of voice therapy is undefined. Further
hormonal supplementation for other indications. Stretching, study is necessary to quantify the risk of voice changes with
massage and manual laryngeal reposturing may be benefi- these treatments and establish a relationship to dose. Patients
cial as adjuncts to relieve compensatory tension habits due receiving androgen supplementation should be counseled
to attempting to speak or sing as patients did prior to the about the potential for voice change which may be irrevers-
administration of testosterone. ible. Therapeutic target levels of serum testosterone should
In patients who returned for follow-up after treatment, be established, and patients who are treated with androgen
there was improvement with hormone therapy discontinua- supplementation may benefit from routine laboratory evalua-
tion and/or voice therapy; however no patient who com- tion to avoid excessively high levels of testosterone which
pleted treatment described that the voice had fully returned could have a virilizing effect.
to normal. This may be a result of the permanent effects of
testosterone on the female larynx.9,23 Although these ACKNOWLEDGMENT
changes can be stopped by discontinuing hormone therapy, Laura Dominguez.
some of the effects may be permanent and irreversible.
This study has several limitations. The presumed causality
between androgen administration and voice complaints rests SUPPLEMENTARY DATA
on the temporal relationship between treatment and symp- Supplementary data related to this article can be found
toms. Some postmenopausal women who are not treated online at https://doi.org/10.1016/j.jvoice.2020.03.008.
with hormone supplementation complain of similar voice
symptoms (lowered pitch, decreased range, and limited upper
register), and have signs of atrophy.23 Some studies have REFERENCES
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