Differential symptom relief profiles of menopausal therapies: an online survey study

doi:10.21203/rs.3.rs-4957731/v1

Background:

While there exist safe hormonal and non-hormonal therapeutic interventions for the menopause, their efficacy profiles are not fully characterized. To use a symptom checklist to examine menopausal symptom relief associated with different treatments.

Methods:

An online survey study was conducted between December 2023 and February 2024. Convenience sampling was conducted, with participants recruited via social media, email, through relevant foundations and support groups, and by word-of-mouth. Inclusion criteria were: (1) ≥ 18 years, (2) assigned female at birth, (3) strong comprehension of the English language, and (4) must be currently experiencing symptoms of the menopause or menopause transition. 3330 respondents consented to participate in the study and of these, 91.95% (N = 3062) who had completed at least 88% of the survey were included in the analysis. Symptom relief per treatment (transdermal hormone replacement therapy (HRT), oral HRT, vaginal HRT, antidepressants, testosterone, cognitive behavioral therapy (CBT)/other therapy/counseling) was assessed using the symptoms included in the Menopause-Specific Quality of Life (MENQOL) questionnaire, which measures four symptom domains: vasomotor, psychosocial, physical, and sexual.

Results:

Data from a total of 3062 respondents were included for analysis (mean age = 51.97, SD = 5.24). Treatment response rates differed significantly across the domains (vasomotor: F(5,2340) = 204.93, p < 0.001, η² = 0.31; psychosocial: F(5,2340) = 75.12, p < 0.001, η² = 0.14; physical: F(5,2340) = 65.46, p < 0.001, η² = 0.12; sexual: F(5,2340) = 89.34, p < 0.001, η² = 0.16). Transdermal HRT performed better at reducing vasomotor symptoms relative to all other options. Regarding psychosocial symptoms, CBT/other therapy/counseling outperformed all other treatment options. The use of transdermal HRT and testosterone was associated with greater response rates in physical symptoms relative to other treatments. Finally, vaginal HRT and testosterone were associated with significantly higher response rates in sexual symptoms in comparison to all other treatments.

Conclusions:

The findings demonstrate differential response rates to menopausal treatments across symptom domains, underscoring the importance of a comprehensive, multidimensional approach to menopausal symptom management. Utilizing a symptom checklist can facilitate the tailoring of treatment plans for specific symptom profiles and patient needs. The outcomes of this study hold considerable implications for improving and shaping treatment guidelines for the menopause.

HRT

hormone replacement therapy

women’s health

menopause

perimenopause

post-menopause

treatment

testosterone

MENQOL

symptom relief

The menopause is characterized by the permanent halt of menstruation. While it typically occurs naturally between the ages of 44 and 55 years¹ due to declining ovarian follicular activity,² the menopause can, for instance, be induced earlier through surgical procedures, medication, or severe illness.³ The perimenopause, also known as the menopause transition, marks the period preceding natural menopause and is characterized by a decrease in ovarian function, resulting in less frequent menstrual cycles.⁴ The post-menopause refers to the period of time after the menopause, when a woman has not had a menstrual cycle for over one year, with women spending approximately one-third of their lifespan in this stage.⁵ Projections indicate that by 2025, the global count of post-menopausal women will surpass 1 billion.⁶

Despite its ubiquitousness, the symptoms linked to the menopause and its transition can pose significant challenges. Up to 80% of women experience difficulties during this period, and 25% categorize these challenges as severe.⁷ Both the perimenopause and post-menopause phases are commonly linked to vasomotor (e.g., hot flushes and night sweats), physical (e.g., tiredness and bone and joint pain), and sexual symptoms (e.g., loss of libido and vaginal dryness during intercourse) that can profoundly affect an individual's quality of life.^8–13 Moreover, the menopause, especially during the transitional period, may elevate the risk of mental health issues,¹⁴ including depression and anxiety^15–17 and even suicidal ideation.¹⁸ Certainly, the menopause is a complex phase of life encompassing not just physical changes but also notable psychological challenges. Acknowledging the holistic nature of menopausal experiences is essential for delivering comprehensive care.

Critically, significant disparities exist in the global availability and licensing of treatment and support options for the menopause.¹⁹ Previous research has indicated that women frequently view their doctors as overly cautious in prescribing hormone-based treatments such as hormone replacement therapy (HRT).^20–22 This is likely due to nearly two decades of pervasive, conflicting, and frequently alarming information about menopause treatment reaching healthcare professionals (HCPs) and the wider public. Notably, HRT remains the most effective treatment for vasomotor symptoms²³ and may also help alleviate menopause-related depressive symptoms,^{24, 25} though there is evidence to suggest that these symptoms could get worse after discontinuation.²⁶

Antidepressants may be a viable treatment option for mood-related menopause symptoms,²⁷ particularly in those presenting with contraindications for HRT. However, there exists controversy over the frequent use of antidepressants for the reduction of mental health symptoms associated with the menopause.^{28, 29} Furthermore, a recent study examining perceptions of healthcare provision for the menopause in the UK demonstrated that women tend to feel dissatisfied with the management of their treatment options for the menopause, often reporting instances where they had perceived that HCPs had made potentially inappropriate recommendations for antidepressants or other psychiatric medication instead of HRT.²¹ These findings suggest that HCPs may be missing opportunities to explain their rationale for selecting antidepressants as a treatment option for menopause, as well as a lack of menopausal women’s awareness regarding the use of antidepressants for the menopause.

For those who prefer non-medical treatment choices for the menopause, cognitive behavioral therapy (CBT) has been deemed a viable option and has been seen to target low mood and anxiety, as well as vasomotor symptoms.³⁰ Notably, findings on the impact of CBT on subjective reports of hot flash frequency have been variable. While some studies have reported reductions in the subjective frequency of hot flashes following CBT,^31–34 others have found no significant effect.^{33, 35} In regards to sexual symptoms related to the menopause, testosterone has been shown to significantly enhance sexual function and is recommended by the National Institute for Health and Care Excellence (NICE) guidelines for menopausal women with low libido when HRT alone is ineffective.^{36, 37} Critically, testosterone therapy for women remains a controversial topic, largely due to the limited long-term safety data available.³⁷ Additionally, most countries only offer formulations designed for men, which can result in women being exposed to supraphysiological blood levels and an increased risk of adverse events.³⁸ Evidently, more research is needed in order to fully understand the effects of testosterone therapy in menopausal women and its long-term safety profile.

Taken together, while evidence supports the efficacy of various menopause treatments, findings are inconsistent across studies, and controversy persists over certain options. Additionally, there is a lack of understanding about women's perceptions of treatment efficacy for specific menopausal symptoms or symptom profiles. This research aimed to address this gap by using a symptom checklist to examine self-reported symptom relief associated with different treatments in a large, multinational sample of menopausal women. The results of this study have significant implications for refining and enhancing treatment guidelines for menopause.

Participants

Participants were recruited between December 2023 and February 2024 via email, paid Facebook and Instagram advertisements, free posts on the Cambridge Centre for Neuropsychiatric Research Facebook and X (formerly known as Twitter) websites, and Reddit. Recruitment messages were also disseminated by word-of-mouth and through relevant foundations and support groups.

Inclusion criteria for the study were: (1) ≥18 years, (2) assigned female at birth, (3) strong comprehension of the English language, and (4) must be currently experiencing symptoms of the menopause or menopause transition (e.g., hot flushes, mood changes, night sweats, irregular or absent periods, decreased sex drive). Participants were also required to not be currently pregnant or breastfeeding or to have given birth in the last year. Participants did not have to have sought help for their menopausal symptoms from a HCP or to have used or taken any treatment or support options for the menopause to take part.

Materials and procedure

An online survey was created using Qualtrics XM®. The survey questions and accompanying study materials were designed in consultation with an experienced psychiatrist (SB). The survey could be completed in 15-20 minutes and was adaptive in nature, such that only relevant questions were asked based on previous responses. For the purpose of the current analysis, only data pertaining to sociodemographic characteristics and symptom relief per treatment option (i.e., transdermal HRT, oral HRT, vaginal HRT, antidepressants, testosterone, and CBT/other type of therapy/counseling) were included.

Menopause status was based on the definitions put forth by the Study of Women’s Health Across the Nation (SWAN),³⁹whereby participants were required to select which of the following options best described their experience of the menopause: a) early perimenopause stage: significant change in the length of menstrual bleed or the time between periods that is not due to pregnancy or breastfeeding, stress or a medical condition; b) late perimenopause stage: no menstrual bleeding in 3-11 months not due to pregnancy or breastfeeding, stress, or a medical condition, c) post-menopause: no menstrual bleeding in 12 months not due to pregnancy or breastfeeding, stress or a medical condition, or d) medically induced menopause: no menstrual bleeding due to hysterectomy with one or two ovaries retained or other medical procedure.

Symptom relief per individual treatment option (current use ≥3months) was assessed using the 29 symptoms included in the Menopause-Specific Quality of Life (MENQOL)⁴⁰ questionnaire, which measures four symptom domains: vasomotor, psychosocial, physical, and sexual. For each treatment option, participants were required to select the symptoms that had improved by ticking a box (ticked=yes, not ticked=no).

Data analytic strategy

Data were processed and analyzed in SPSS version 28.0.1.1. and R 4.3.0. Symptom domain relief scores were calculated by summing the presence of improvements (yes/no) in symptoms pertaining to each domain. Scores were scaled between 0 and 1 for comparability across the four domains. Differences in symptom domain relief scores by treatment option (current use ≥3months) were analyzed using one-way ANCOVAs, with effect sizes reported as eta-squared (η²; small=0.01, medium=0.06, large=0.14).⁴¹The analysis was adjusted for age, gender, country of residence, menopause status (perimenopause/post-menopause/medically-induced menopause), ethnicity, education, employment, and concurrent use of menopausal treatments (yes/no; number). Pairwise post-hoc comparisons between treatments were adjusted for multiple comparisons using the Bonferroni correction.

To account for the potential use of hormonal treatments in respondents that respondents who did not identify as women may have been taking or using concurrently, analyses were repeated excluding those who identified as men, non-binary, and other, and well as those who selected ‘prefer not to answer’.

Ethical approval and informed consent

The study was approved by the University of Cambridge Psychology Research Ethics Committee (approval number PRE.2023.123). All participants provided informed consent electronically to participate in the study.

Overview

3330 respondents consented to participants in the study. 91.95% (N=3062) who had completed at least 88% of the survey were included in the analysis.

Respondents’ sociodemographic and treatment characteristics are shown in Table 1. The mean age was 51.97 (SD=5.24), with the majority of respondents identifying with the female gender (98.76%, n=3024), being white (90.01%, n=2756), having at least an undergraduate degree (69.17%, n=2118), and being in current employment (i.e., full-time, part-time, self-employed; 80.96%, n=2479).

81.16% (n=2485) of participants had discussed their menopausal symptoms with a HCP. Of these, 76.70% (n=1906) had been prescribed treatment, with the most common treatment options (i.e., current or past use) being transdermal HRT (69.66%, n=1247), oral HRT (47.43%, n=849), and antidepressants (40.46%, n=726). For an overview of respondents’ concurrent treatment use see Supplementary Figure 1 (Supplementary Information).

Table 1. Sociodemographic and treatment characteristics (N=3062)
	M (SD)
Age		51.97 (5.24)
	n (%)
Gender	Woman	3024 (98.76)
	Man	5 (0.16)
	Non-binary	20 (0.65)
	Other	3 (0.10)
	Prefer not to answer	10 (0.33)
Country of residence	Australia	508 (16.59)
	Canada	537 (17.54)
	New Zealand	508 (16.59)
	United Kingdom	735 (24.00)
	United States of America	774 (25.28)
Menopause status	Perimenopause	1387 (45.30)
	Post-menopause	1218 (39.78)
	Medically-induced menopause	457 (14.92)
Ethnicity	White/Caucasian	2756 (90.01)
	Asian	48 (1.57)
	Black/Caribbean/African	22 (0.72)
	Arab/Middle Eastern/North African descent	7 (0.23)
	Hispanic/Latinx	43 (1.40)
	Mixed/multiple	133 (4.34)
	Other	37 (1.21)
	I am not sure	2 (0.07)
	Prefer not to answer	14 (0.46)
Education	≤ Primary (up to 11 years)	53 (1.73)
	Lower secondary (up to 16 years)	240 (7.84)
	Upper secondary (up to 18 years)	448 (14.63)
	Undergraduate/college degree (i.e., Bachelors)	1207 (39.42)
	Postgraduate degree (e.g., Masters, PhD)	911 (29.75)
	Other	146 (4.77)
	Prefer not to answer	57 (1.86)
Employment ^a	Full-time	1536 (49.84)
	Part-time	574 (18.75)
	Self-employed	369 (12.05)
	Parental leave/caring responsibilities	46 (1.50)
	Homemaker	268 (8.75)
	Student	40 (1.31)
	Voluntary work	86 (2.81)
	Retired	214 (6.99)
	Unemployed	112 (3.66)
	Prefer not to answer	70 (2.29)
Seen HCP for menopause symptoms	Yes	2485 (81.16)
Seen HCP for menopause symptoms	No	577 (18.84)
Been prescribed treatment/support for the menopause ^b	Yes	1906 (76.70)
Been prescribed treatment/support for the menopause ^b	No	579 (23.30)
Transdermal HRT ^c	Yes, currently using	1025 (57.26)
	Yes, in the past	222 (12.40)
	No, never	543 (30.34)
Oral HRT ^c	Yes, currently using	564 (31.51)
	Yes, in the past	285 (15.92)
	No, never	941 (52.57)
Vaginal HRT ^c	Yes, currently using	441 (24.64)
	Yes, in the past	205 (11.45)
	No, never	1144 (63.91)
Antidepressants ^c	Yes, currently using	432 (24.13)
	Yes, in the past	294 (16.42)
	No, never	1064 (59.44)
Testosterone ^c	Yes, currently using	226 (12.63)
	Yes, in the past	94 (5.25)
	No, never	1470 (82.12)
CBT/other therapy/counseling ^c	Yes, currently using	210 (11.73)
	Yes, in the past	354 (19.78)
	No, never	1226 (68.49)
Length of current transdermal HRT use ^d	Less than 3 months	154 (15.02)
	3 – 6 months	140 (13.66)
	6 months – 1 year	216 (21.07)
	1 – 2 years	284 (27.71)
	More than 2 years	231 (22.54)
Length of current oral HRT use ^e	Less than 3 months	92 (16.37)
	3 – 6 months	80 (14.24)
	6 months – 1 year	106 (18.86)
	1 – 2 years	142 (25.27)
	More than 2 years	142 (25.27)
Length of current vaginal HRT use ^f	Less than 3 months	94 (21.32)
	3 – 6 months	66 (14.97)
	6 months – 1 year	91 (20.64)
	1 – 2 years	90 (20.41)
	More than 2 years	100 (22.68)
Length of current antidepressant use ^g	Less than 3 months	76 (17.59)
	3 – 6 months	31 (7.18)
	6 months – 1 year	66 (15.28)
	1 – 2 years	74 (17.13)
	More than 2 years	185 (42.82)
Length of current testosterone use ^h	Less than 3 months	46 (20.35)
	3 – 6 months	41 (18.14)
	6 months – 1 year	49 (21.68)
	1 – 2 years	44 (19.47)
	More than 2 years	46 (20.35)
Length of current CBT/other therapy/counseling use ⁱ	Less than 3 months	59 (28.64)
	3 – 6 months	31 (15.05)
	6 months – 1 year	31 (15.05)
	1 – 2 years	32 (15.53)
	More than 2 years	53 (25.73)

Note. CBT, cognitive behavioral therapy; HCP, health care professional; HRT, hormone replacement therapy
Key. ^aPercentages add to more than 100% as participants could select multiple options; ^bincludes those who had visited a HCP for their menopausal symptoms (n=2485); ^cincludes those who had been prescribed treatment/support for the menopause (n=1790; 116 respondents selected ‘other’ treatment and were not included); ^d includes those who were currently using transdermal HRT (n=1025); ^e includes those who were currently taking oral HRT (n=562; missing data from two respondents as they had initially selected ‘past use’ but open-ended responses suggested ongoing use); ^f includes those who were currently using vaginal HRT (n=441); ^g includes those who were currently taking antidepressants (n=432); ^h includes those who were currently using testosterone (n=226);ⁱ includes those who were currently using CBT/other therapy/counseling (n=206; missing data from four respondents as they had initially selected ‘past use’ but open-ended responses suggested ongoing use)

[Table 1]

Symptom relief

An overview of menopausal symptom relief per treatment option is shown in Figure 1 and Supplementary Table 1 (Supplementary Information). Response rates for the treatment options differed significantly across the domains (vasomotor: F(5,2340)=204.93, p<0.001, η²=0.31; psychosocial: F(5,2340)=75.12, p<0.001, η²=0.14; physical: F(5,2340)=65.46, p<0.001, η²=0.12; sexual: F(5,2340)=89.34, p<0.001, η²=0.16).

[Figure 1]

For an overview of Bonferroni-corrected pairwise post-hoc comparisons see Figure 2 and Tables 2 and 3. Regarding vasomotor symptoms, the use of transdermal HRT was associated with greater response rates relative to all other treatment options (all p≤0.02), while the use of oral HRT was related with higher response rates in comparison to vaginal HRT, antidepressants, testosterone, and CBT/other therapy/counseling (all p≤0.001).

In terms of psychosocial symptoms, CBT/other therapy/counseling outperformed all other treatment options (all p≤0.001), while both transdermal HRT and antidepressant use were associated with significantly higher response rates in comparison to oral HRT, vaginal HRT, and testosterone (all p<0.001). Oral HRT use was seen to be related with greater response rates for psychosocial symptoms than vaginal HRT (p<0.001).

Testosterone medication was associated with significantly greater response rates for physical symptoms relative to oral HRT, vaginal HRT, antidepressants, and CBT/other therapy/counseling (all p≤0.01). The use of transdermal and oral HRT were related to significantly higher response rates for physical symptoms in comparison to vaginal HRT, antidepressants, and CBT/other therapy/counseling (all p<0.001), while transdermal HRT was further associated with better response rates for physical symptoms relative to oral HRT (p<0.001).

Finally, in terms of sexual symptoms, vaginal HRT and testosterone were both independently associated with significantly higher response rates in comparison to all other treatment options (all p<0.001). Both transdermal and oral HRT significantly outperformed antidepressants, demonstrating greater response rates for sexual symptoms (all p<0.001), while transdermal HRT use was also associated with significantly greater response rates than oral HRT for sexual symptoms (p<0.001).

In order to account for the potential use of hormonal treatments that respondents who did not identify as women may have been taking or using concurrently, analyses were repeated excluding those who identified as men, non-binary, and other, as well as those who selected ‘prefer not to answer’. All findings from the original analysis remained significant.

[Figure 2]

Table 2. Mean response rate per treatment for each MENQOL symptom domain (current use ≥3months)
MENQOL symptom domain	Treatment	Mean response rate ^a	95% CI
Vasomotor	Transdermal HRT	0.46	0.44 – 0.48
	Oral HRT	0.41	0.38 – 0.43
	Vaginal HRT	0.05	0.02 – 0.08
	Antidepressants	0.04	0.01 – 0.07
	Testosterone	0.08	0.04 – 0.12
	CBT/other therapy/counseling	0.02	-0.03 – 0.07
Psychosocial	Transdermal HRT	0.27	0.25 – 0.28
	Oral HRT	0.16	0.14 – 0.18
	Vaginal HRT	0.02	0.00 – 0.05
	Antidepressants	0.27	0.25 – 0.30
	Testosterone	0.17	0.13 – 0.20
	CBT/other therapy/counseling	0.37	0.33 – 0.41
Physical	Transdermal HRT	0.14	0.13 – 0.15
	Oral HRT	0.10	0.09 – 0.11
	Vaginal HRT	0.04	0.02 – 0.05
	Antidepressants	0.03	0.02 – 0.05
	Testosterone	0.14	0.12 – 0.16
	CBT/other therapy/counseling	0.02	0.00 – 0.04
Sexual	Transdermal HRT	0.14	0.12 – 0.15
	Oral HRT	0.08	0.06 – 0.10
	Vaginal HRT	0.31	0.29 – 0.34
	Antidepressants	0.01	-0.01 – 0.04
	Testosterone	0.27	0.24 – 0.30
	CBT/other therapy/counseling	0.02	-0.02 – 0.06

Note. CBT, cognitive behavioral therapy; CI, confidence interval; HRT, hormone replacement therapy
Key. ^aScaled to 0-1 and adjusted for the covariates (age, gender, country of residence, menopause status (perimenopause/post-menopause/medically-induced menopause), ethnicity, education, employment, and concurrent use of menopausal treatment (yes/no; number)

Table 3. Mean differences in response rates between treatments per MENQOL symptom domain (current use ≥3months)
MENQOL symptom domain	Treatment comparisons ^a		Mean difference ^b	95% CI	p
Vasomotor	Transdermal HRT	Oral HRT	0.05	0.00 – 0.10	0.023*
	Transdermal HRT	Vaginal HRT	0.41	0.35 – 0.47	<0.001***
	Transdermal HRT	Antidepressants	0.42	0.36 – 0.47	<0.001***
	Transdermal HRT	Testosterone	0.38	0.31 – 0.46	<0.001***
	Transdermal HRT	CBT/other therapy/counseling	0.44	0.36 – 0.52	<0.001***
	Oral HRT	Vaginal HRT	0.36	0.30 – 0.42	<0.001***
	Oral HRT	Antidepressants	0.37	0.30 – 0.43	<0.001***
	Oral HRT	Testosterone	0.33	0.25 – 0.41	<0.001***
	Oral HRT	CBT/other therapy/counseling	0.39	0.30 – 0.47	<0.001***
	Vaginal HRT	Antidepressants	0.01	-0.06 – 0.08	1.000
	Vaginal HRT	Testosterone	-0.03	-0.11 – 0.05	1.000
	Vaginal HRT	CBT/other therapy/counseling	0.03	-0.06 – 0.11	1.000
	Antidepressants	Testosterone	-0.04	-0.12 – 0.04	1.000
	Antidepressants	CBT/other therapy/counseling	0.02	-0.07 – 0.11	1.000
	Testosterone	CBT/other therapy/counseling	0.06	-0.04 – 0.15	1.000
Psychosocial	Transdermal HRT	Oral HRT	0.11	0.07 – 0.15	<0.001***
	Transdermal HRT	Vaginal HRT	0.24	0.20 – 0.29	<0.001***
	Transdermal HRT	Antidepressants	0.00	-0.05 – 0.04	1.000
	Transdermal HRT	Testosterone	0.10	0.04 – 0.16	<0.001***
	Transdermal HRT	CBT/other therapy/counseling	-0.10	-0.16 – -0.04	<0.001***
	Oral HRT	Vaginal HRT	0.14	0.09 – 0.18	<0.001***
	Oral HRT	Antidepressants	-0.11	-0.16 – -0.06	<0.001***
	Oral HRT	Testosterone	-0.01	-0.07 – 0.05	<0.001***
	Oral HRT	CBT/other therapy/counseling	-0.21	-0.27 – -0.14	<0.001***
	Vaginal HRT	Antidepressants	-0.25	-0.30 – -0.20	<0.001***
	Vaginal HRT	Testosterone	-0.15	-0.21 – -0.08	<0.001***
	Vaginal HRT	CBT/other therapy/counseling	-0.34	-0.41 – -0.27	<0.001***
	Antidepressants	Testosterone	0.10	0.04 – 0.17	<0.001***
	Antidepressants	CBT/other therapy/counseling	-0.10	-0.16 – -0.03	0.001**
	Testosterone	CBT/other therapy/counseling	-0.20	-0.27 – -0.12	<0.001***
Physical	Transdermal HRT	Oral HRT	0.04	0.02 – 0.06	<0.001***
	Transdermal HRT	Vaginal HRT	0.10	0.08 – 0.13	<0.001***
	Transdermal HRT	Antidepressants	0.11	0.08 – 0.13	<0.001***
	Transdermal HRT	Testosterone	0.00	-0.03 – 0.03	1.000
	Transdermal HRT	CBT/other therapy/counseling	0.12	0.09 – 0.16	<0.001***
	Oral HRT	Vaginal HRT	0.06	0.04 – 0.09	<0.001***
	Oral HRT	Antidepressants	0.07	0.04 – 0.09	<0.001***
	Oral HRT	Testosterone	-0.04	-0.07 – -0.01	0.006**
	Oral HRT	CBT/other therapy/counseling	0.08	0.04 – 0.12	<0.001***
	Vaginal HRT	Antidepressants	0.00	-0.03 – 0.03	1.000
	Vaginal HRT	Testosterone	-0.10	-0.14 – -0.07	<0.001***
	Vaginal HRT	CBT/other therapy/counseling	0.02	-0.02 – 0.05	1.000
	Antidepressants	Testosterone	-0.11	-0.14 – -0.07	<0.001***
	Antidepressants	CBT/other therapy/counseling	0.02	-0.02 – 0.05	1.000
	Testosterone	CBT/other therapy/counseling	0.12	0.08 – 0.16	<0.001***
Sexual	Transdermal HRT	Oral HRT	0.06	0.02 – 0.09	<0.001***
	Transdermal HRT	Vaginal HRT	-0.18	-0.22 – -0.13	<0.001***
	Transdermal HRT	Antidepressants	0.12	0.08 – 0.16	<0.001***
	Transdermal HRT	Testosterone	-0.13	-0.19 – -0.08	<0.001***
	Transdermal HRT	CBT/other therapy/counseling	0.12	0.06 – 0.18	<0.001***
	Oral HRT	Vaginal HRT	-0.23	-0.28 – -0.19	<0.001***
	Oral HRT	Antidepressants	0.07	0.02 – 0.11	<0.001***
	Oral HRT	Testosterone	-0.19	-0.24 – -0.13	<0.001***
	Oral HRT	CBT/other therapy/counseling	0.06	0.00 – 0.12	0.053
	Vaginal HRT	Antidepressants	0.30	0.25 – 0.35	<0.001***
	Vaginal HRT	Testosterone	0.04	-0.02 – 0.10	0.459
	Vaginal HRT	CBT/other therapy/counseling	0.29	0.23 – 0.36	<0.001***
	Antidepressants	Testosterone	-0.26	-0.32 – -0.19	<0.001***
	Antidepressants	CBT/other therapy/counseling	-0.01	-0.07 – 0.06	1.000
	Testosterone	CBT/other therapy/counseling	0.25	0.18 – 0.32	<0.001***

Note. CBT, cognitive behavioral therapy; CI, confidence interval; HRT, hormone replacement
Key. ^aPost-hoc pairwise comparisons, subject to the Bonferroni-correction method; ^bScaled to 0-1 and adjusted for the covariates (age, gender, country of residence, menopause status (perimenopause/post-menopause/medically-induced menopause), ethnicity, education, employment, and concurrent use of menopausal treatment (yes/no; number); * p<0.05; ** p<0.01; *** p<0.001

[Table 3]

The current study aimed to examine self-reported menopausal symptom relief across various treatment options using a symptom checklist in a large multinational sample of menopausal women. The findings from this research highlight differential response rates to menopausal treatments across various symptom domains, underscoring the necessity of a comprehensive, multidimensional approach to menopausal symptom management. Overall, the outcomes of this study hold considerable implications for improving and shaping treatment guidelines for menopause, promoting a more individualized and effective approach to care that enhances the quality of life for menopausal women worldwide.

HCPs may want to prioritize the use of transdermal HRT due to its broad symptom response rates and integrate psychological therapies into menopause management for a more holistic approach. In fact, while transdermal HRT and antidepressant use demonstrated similar response rates for psychosocial symptoms, psychological therapies appeared to be associated with even greater response rates. These therapies not only help address psychosocial symptoms but also empower women to develop new coping strategies and adopt more positive thinking styles, offering benefits beyond those provided by purely biological treatments, both hormonal and non-hormonal.^{42, 43} Critically, in the current study, the use of psychological therapies was relatively low. To improve accessibility, alternative delivery methods such as online platforms or hybrid models that combine both in-person and online sessions could be explored. Research has shown that patients appreciate the independence and empowerment provided by online platforms.⁴⁴ Online applications offer the convenience of access from anywhere with an internet connection, which is particularly beneficial for individuals in remote locations or those with limited mobility.⁴⁵ Additionally, online psychological therapies allow women to engage in therapy on their own schedules, making it easier for those with busy lifestyles or difficulties attending traditional sessions regularly.⁴⁶

The effectiveness of testosterone and vaginal HRT in addressing sexual dysfunction suggests that these treatments could be integral components of care plans for menopausal women experiencing such symptoms. Notably, testosterone appears effective in alleviating both physical and sexual symptoms, making it a valuable option for a comprehensive treatment strategy. However, despite being recognized as a suitable adjunct to menopause care, NICE guidelines lack detailed information on prescribing testosterone, appropriate products and dosages, and monitoring requirements.²⁷ Furthermore, there is a lack of long-term safety data for use of testosterone for relief of menopausal symptoms,⁴⁷ highlighting the need for further research and clearer clinical guidelines.

Taken together, expanding treatment plans to include a variety of options may ensure that menopausal women receive tailored care that effectively addresses their specific symptom profiles and preferences. In particular, utilizing a symptom checklist can further enhance the customization of treatment plans by allowing HCPs to accurately identify and address the unique combination of symptoms experienced by each patient. Moreover, completing these checklists prior to appointments could save valuable clinician time, allowing HCPs to focus more on discussing and implementing treatment strategies, as well promoting shared decision-making, rather than the identification of troublesome symptoms.

Notably, pre-consultation interventions, such as checklists, have been shown to increase patient satisfaction in healthcare settings.⁴⁸ For instance, checklists provide a pragmatic method for identifying issues in post-stroke patients,⁴⁹ facilitating referrals to appropriate support services and structuring stroke reviews using a patient-centered approach. Similarly, symptom checklists have been effective in helping clinicians make diagnostic and treatment decisions for primary care patients who report daily cannabis and/or other drug use.⁵⁰ By systematically evaluating and tracking symptoms, clinicians can adjust treatments in real-time, ensuring optimal relief and improved patient outcomes. This personalized method not only fosters a more patient-centered approach but is also likely to result in higher levels of satisfaction and adherence to treatment plans. By incorporating symptom checklists and a variety of treatment options, HCPs can deliver more comprehensive and responsive care, ultimately enhancing the quality of life for menopausal women.

Limitations

The experiences captured in this study may not fully represent the broader populations of the surveyed countries, including ethnic minorities and disadvantaged groups.⁵¹ Additionally, while social media recruitment and online survey delivery were employed to maximize the sample size, this approach likely introduced recruitment bias. For example, individuals with negative experiences of menopausal treatment may have been more inclined to participate. Furthermore, the symptom relief data were self-reported and retrospective, potentially introducing biases and inaccuracies. Additionally, it is worth mentioning that all but one of the symptoms in the MENQOL are negatively worded or presented as unwanted symptoms. It remains unclear whether respondents interpret the remaining item: "a change in sexual desire", as a negative or positive symptom. These factors should be considered when interpreting the findings.

This study investigated how well different treatments relieve menopausal symptoms across women from multiple countries using a symptom checklist while adjusting for the relevant covariates, with the overall findings highlighting the need for a comprehensive approach to managing menopause symptoms. HCPs should prioritize the use of transdermal HRT for the alleviation of more global menopausal symptoms, while incorporating psychological therapies and vaginal HRT or testosterone as needed for potential psychosocial and sexual symptoms, respectively. Finally, using a menopausal symptom checklist has the potential to facilitate the customization of treatment.

CBT: cognitive behavioral therapy

HCP: healthcare professional

HRT: hormone replacement therapy

MENQOL: Menopause-Specific Quality of Life questionnaire

NICE: National Institute for Health and Care Excellence

SWAN: Study of Women’s Health Across the Nation

Ethics approval and consent to participate

The study was approved by the University of Cambridge Psychology Research Ethics Committee (approval number PRE.2023.123). All participants provided informed consent electronically to participate in the study.

Consent for publication

Not applicable.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

Author SB holds shares in Psyomics Ltd but declares no non-financial competing interests. Author EF is a paid consultant for Psyomics Ltd but declares no non-financial competing interests. Author JT received payment for licensing unrelated research data to Psyomics Ltd. Author NM-K declares no financial or non-financial competing interests.

Funding

This work was supported by grant 07R-1888 from the Stanley Medical Research Institute. The Stanley Medical Research Institute had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript and decision to submit the manuscript for publication.

Authors' contributions

Authors NM-K, EF, and JT had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: NM-K, EF, SB. Drafting of the manuscript: All authors. Critical review of the manuscript for important intellectual content: All authors. Statistical analysis: NM-K and JT. Obtained funding: SB.

Acknowledgements

Not applicable.

Hardy C, Hunter MS, Griffiths A. Menopause and work: an overview of UK guidance. Occupational Medicine. 2018 Dec;68(9):580–6.
World Health Organization. World Health Report 2008: Women, Ageing and Health: A Framework for Action. 2008. Available from: https://apps.who.int/iris/bitstream/handle/10665/43810/9789241563529_eng.pdf [Accessed 24 March 2024].
Hoga L, Rodolpho J, Gonçalves B, Quirino B. Womenʼs experience of menopause: a systematic review of qualitative evidence. JBI Database of Systematic Reviews and Implementation Reports. 2015 Aug;13(8):250–337.
Burger HG, Hale GE, Dennerstein L, Robertson DM. Cycle and hormone changes during perimenopause: the key role of ovarian function. Menopause. 2008;15(4 Pt 1):603–12.
Soules MR, Sherman S, Parrott E, Rebar R, Santoro N, Utian W, et al. Executive summary: stages of reproductive aging workshop (STRAW). Fertility and Sterility. 2001 Nov;76(5):874–8.
Shifren JL, Gass MLS. The North American Menopause Society Recommendations for Clinical Care of Midlife Women. Menopause. 2014 Oct;21(10):1038–62.
Avis NE, Crawford SL, Greendale G, Bromberger JT, Everson-Rose SA, Gold EB, et al. Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition. JAMA Internal Medicine. 2015 Apr 1;175(4):531.
Dave FG, Adedipe T, Disu S, Laiyemo R. Unscheduled bleeding with hormone replacement therapy. The Obstetrician & Gynaecologist. 2019 Apr;21(2):95–101.
Karaçam Z, Şeker SE. Factors associated with menopausal symptoms and their relationship with the quality of life among Turkish women. Maturitas. 2007 Sep;58(1):75–82.
Avis NE, Ory M, Matthews KA, Schocken M, Bromberger J, Colvin A. Health-Related Quality of Life in a Multiethnic Sample of Middle-Aged Women. Medical Care. 2003 Nov;41(11):1262–76.
Avis NE, Colvin A, Bromberger JT, Hess R, Matthews KA, Ory M, et al. Change in health-related quality of life over the menopausal transition in a multiethnic cohort of middle-aged women. Menopause. 2009 Sep;16(5):860–9.
Williams RE, Levine KB, Kalilani L, Lewis J, Clark RV. Menopause-specific questionnaire assessment in US population-based study shows negative impact on health-related quality of life. Maturitas. 2009 Feb;62(2):153–9.
Daly E, Gray A, Barlow D, McPherson K, Roche M, Vessey M. Measuring the impact of menopausal symptoms on quality of life. BMJ. 1993 Oct 2;307(6908):836–40.
Soares CN. Depression and Menopause. Medical Clinics of North America. 2019 Jul;103(4):651–67.
Soares CN. Depression and Menopause. Medical Clinics of North America. 2019 Jul;103(4):651–67.
Bromberger JT, Kravitz HM, Chang YF ., Cyranowski JM, Brown C, Matthews KA. Major depression during and after the menopausal transition: Study of Women’s Health Across the Nation (SWAN). Psychological Medicine. 2011 Feb 9;41(09):1879–88.
Hart J. Menopause: Shifting Hormones Linked to Anxiety and Depression Symptoms. Alternative and Complementary Therapies. 2019 Sep 11;25(5): 254-256.
Usall J, Pinto-Meza A, Fernández A, Graaf R de, Demyttenaere K, Alonso J, et al. Suicide ideation across reproductive life cycle of women Results from a European epidemiological study. Journal of Affective Disorders. 2009 Jul;116(1-2):144–7.
Hamoda H. Availability of menopausal hormone therapy products worldwide. Maturitas. 2020 Feb;141:87-88
Duffy O, Iversen L, Hannaford PC. The menopause “It’s somewhere between a taboo and a joke”. A focus group study. Climacteric. 2011 Mar 13;14(4):497–505.
Martin-Key NA, Funnell EL, Spadaro B, Bahn S. Perceptions of healthcare provision throughout the menopause in the UK: a mixed-methods study. npj Women’s Health. 2023 Dec 7;1(1):1–10.
Hyde A, Nee J, Drennan J, Butler M, Howlett E. Hormone therapy and the medical encounter. Menopause. 2010 Mar;17(2):344–50.
Caretto M, Simoncini T. Hormone Replacement Therapy (HRT). Endocrinology. 2020 Jan 1;1–18.
Schmidt PJ, Nieman L, Danaceau MA, Tobin MB, Roca CA, Murphy JH, et al. Estrogen replacement in perimenopause-related depression: A preliminary report. American Journal of Obstetrics and Gynecology. 2000 Aug;183(2):414–20.
Soares C, Almeida OP, Joffe H, Cohen LS. Efficacy of Estradiol for the Treatment of Depressive Disorders in Perimenopausal Women. Archives of General Psychiatry. 2001 Jun 1;58(6):529.
Schmidt PJ, Ben Dor R, Martinez PE, Guerrieri GM, Harsh VL, Thompson K, et al. Effects of Estradiol Withdrawal on Mood in Women With Past Perimenopausal Depression. JAMA Psychiatry. 2015 Jul 1;72(7):714.
NICE. Overview | Menopause: diagnosis and management | Guidance | NICE [Internet]. Nice.org.uk. NICE; 2019. Available from: https://www.nice.org.uk/guidance/ng23
Graziottin A, Serafini A. Depression and the menopause: why antidepressants are not enough? Menopause International. 2009 May 22;15(2):76–81.
Glynne S, Newson L. Curb antidepressant use: perimenopausal women may benefit from HRT. BMJ. 2024 Jan 29;384:q220.
National Institute for Health and Care Excellence. Clinical knowledge summary. Hormone replacement therapy (HRT). 2022. Available from: https://cks.nice.org.uk/topics/menopause/prescribing-information/hormone-replacement-therapy-hrt/ [Accessed 3 April 2024].
Hunter MS, Liao K-M. Evaluation of a four-session cognitive-behavioral intervention for menopausal hot flushes. Br J Health Psychol. 1996 May;1:113–25.
Stefanopoulou E, Hunter MS. Telephone-guided Self-Help Cognitive Behavioural Therapy for menopausal symptoms. Maturitas. 2014 Jan;77(1):73–7.
Hardy C, Griffiths A, Norton S, Hunter MS. Self-help cognitive behavior therapy for working women with problematic hot flushes and night sweats (MENOS@Work): a multicenter randomized controlled trial. Menopause. 2018 May;25(5):508–19.
Hunter MS, Coventry S, Hamed H, Fentiman I, Grunfeld EA. Evaluation of a group cognitive behavioural intervention for women suffering from menopausal symptoms following breast cancer treatment. Psycho-Oncology. 2009 May;18(5):560–3.
Ayers B, Smith M, Hellier J, Mann E, Hunter MS. Effectiveness of group and self-help cognitive behavior therapy in reducing problematic menopausal hot flushes and night sweats (MENOS 2). Menopause: The Journal of The North American Menopause Society. 2012 Jul;19(7):749–59.
Lumsden MA, Davies M, Sarri G; Guideline Development Group for Menopause: Diagnosis and Management (NICE Clinical Guideline No. 23). Diagnosis and Management of Menopause: The National Institute of Health and Care Excellence (NICE) Guideline. JAMA Intern Med. 2016 Aug;176(8):1205-1206.
Scott A, Newson L. Should we be prescribing testosterone to perimenopausal and menopausal women? A guide to prescribing testosterone for women in primary care. British Journal of General Practice. 2020 Mar 26;70(693):203–4.
Islam RM, Bell RJ, Green S, Page MJ, Davis SR. Safety and efficacy of testosterone for women: a systematic review and meta-analysis of randomised controlled trial data. The Lancet Diabetes & Endocrinology. 2019 Jul;7(10).
El Khoudary SR, Greendale G, Crawford SL, Avis NE, Brooks MM, Thurston RC, et al. The menopause transition and womenʼs health at midlife. Menopause. 2019 Oct;26(10):1213–27.
Hilditch JR, Lewis J, Peter A, van Maris B, Ross A, Franssen E, et al. A menopause-specific quality of life questionnaire: development and psychometric properties. Maturitas. 1996 Jul;24(3):161–75.
Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd ed. New York: Academic Press; 1988.
Spector A, Li Z, He L, Badawy Y, Desai R. The effectiveness of psychosocial interventions on non-physiological symptoms of menopause: A systematic review and meta-analysis. Journal of Affective Disorders. 2024 May 1;352:460–72.
Balabanovic J, Ayers B, Hunter MS. Cognitive Behaviour Therapy for Menopausal Hot Flushes and Night Sweats: A Qualitative Analysis of Women’s Experiences of Group and Self-Help CBT. Behavioural and Cognitive Psychotherapy. 2012 Sep 4;41(4):441–57.
Knowles SE, Toms G, Sanders C, Bee P, Lovell K, Rennick-Egglestone S, et al. Qualitative Meta-Synthesis of User Experience of Computerised Therapy for Depression and Anxiety. Harris F, editor. PLoS ONE. 2014 Jan 17;9(1):e84323.
Kim JH, Yu HJ. The Effectiveness of Cognitive Behavioral Therapy on Depression and Sleep Problems for Climacteric Women: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine. 2024 Jan 15;13(2):412.
Martin-Key NA, Spadaro B, Schei TS, Bahn S. Proof-of-Concept Support for the Development and Implementation of a Digital Assessment for Perinatal Mental Health: Mixed Methods Study. Journal of Medical Internet Research. 2021 Jun 4;23(6):e27132.
Davis SR, Wahlin-Jacobsen S. Testosterone in women--the clinical significance. The lancet Diabetes & endocrinology. 2015;3(12):980–92.
Kinnersley P, Edwards A, Hood K, Ryan R, Prout H, Cadbury N, et al. Interventions before consultations to help patients address their information needs by encouraging question asking: systematic review. BMJ. 2008 Jul 16;337(jul16 1):a485–5.
Turner GM, Mullis R, Lim L, Kreit L, Mant J. Using a checklist to facilitate management of long-term care needs after stroke: insights from focus groups and a feasibility study. BMC Family Practice. 2019 Jan 4;20(1).
Matson TE, Hallgren KA, Lapham GT, Oliver M, Wang X, Williams EC, et al. Psychometric Performance of a Substance Use Symptom Checklist to Help Clinicians Assess Substance Use Disorder in Primary Care. JAMA network open. 2023 May 26;6(5):e2316283–3.
Pershad A, Morris JM, Pace D, Khanna P. Racial disparities in menopausal hormone therapy acceptance: a pilot study. Menopause. 2022 Sep 6;29(11):1263–8.

Competing interest reported. Author SB holds shares in Psyomics Ltd but declares no non-financial competing interests. Author EF is a paid consultant for Psyomics Ltd but declares no non-financial competing interests. Author JT received payment for licensing unrelated research data to Psyomics Ltd. Author NM-K declares no financial or non-financial competing interests.

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Differential symptom relief profiles of menopausal therapies: an online survey study

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