A direct comparison of women’s perceptions and acceptability of micronised progesterone and medroxyprogesterone acetate in combination with transdermal oestradiol in the management of young postmenopausal women,under 45 years of age

Abstract

Objective

To assess the acceptability and perception of postmenopausal women, to two different hormone replacement therapy regimens, in relation to the control of their symptoms and development of adverse effects.

Study design

Prospectively recruited postmenopausal women, <45 years, were randomised to one of two treatment arms for 12-months: cyclical micronised progesterone or medroxyprogesterone acetate in combination with transdermal oestradiol. A self-reported questionnaire with matrix rating scales was completed and repeated after 3, 6 and 12-months.

Main outcome measures

Symptom control and development of adverse effects.

Results

Seventy-one individuals were screened, with baseline data available for 67 subjects. A total of 190 questionnaires were returned. The most commonly reported symptoms were low energy levels, vasomotor symptoms and sexual dysfunction. The prevalence of adverse effects ranged between 57.89 and 87.50%, with a reduction seen in the transdermal oestradiol + micronised progesterone arm (73.91% at 3-months, decreasing to 57.89% at 12-months; p = 0.33), compared to the transdermal oestradiol + medroxyprogesterone acetate arm (76.92% at 3-months, increasing to 87.50% at 12-months; p = 0.69). The main reported adverse effects were bloating, weight change and psychological symptoms. A significant difference was documented between the groups after set intervals, with a greater proportion reporting breast tenderness after 3-months (p = 0.01), lower numbers reporting mood swings at 6-months (p = 0.01) and irritability at 12-months (p = 0.03) in the transdermal oestradiol + micronised progesterone arm compared to the transdermal oestradiol + medroxyprogesterone acetate arm.

Conclusions

The acceptability of both regimens was high despite adverse effects, but tolerability of transdermal oestradiol combined with micronised progesterone appeared to be better with fewer women reporting psychological concerns.

Keywords

Adverse effects medroxyprogesterone acetate micronised progesterone quality of life

Introduction

The primary indication for hormone replacement therapy (HRT) in postmenopausal women is symptom relief, with an estimated 75% reported to experience vasomotor type symptoms.^1,2 A Cochrane systematic review, including 24 trials, demonstrated a 75% (95% confidence interval (CI) 64.3–82.3) reduction in hot flushes with HRT compared to placebo (57.7% reduction, 95% CI 45.1–67.7).³ Young postmenopausal women, diagnosed with premature ovarian insufficiency (POI) or those who have undergone an early menopause (EM) (EMPOI), represent a subset population, in whom the mainstay of management is to provide physiological levels of the deficient hormones and thus, help counteract the effects of the long-term sequelae of estrogen deficiency.

HRT, in postmenopausal women under 45 years of age, is recommended at least until the average age of the menopause.^1,2,4–7 The majority of data used to counsel these women on the benefits and risk profile associated with its use are extrapolated from studies conducted in older postmenopausal women.⁸

Women with an intact uterus are prescribed a combination of estrogen and progestogen to reduce the risk of endometrial cancer development^9,10 (relative risk 2.1–5.7)⁹ by opposing the proliferative effects of estrogen.^10,11 There are many different classes of progestogens, each with different pharmacological properties dependent upon the parent molecule from which they are derived, testosterone or progesterone, and thus, accounting for their different side effect profiles.^11,12

The biological actions of natural progesterone (micronised progesterone (MP)) are said to be more selective with less interaction with androgenic and mineralocorticoid receptors compared with other progestogens. In contrast, medroxyprogesterone acetate (MPA) has slight androgenic and glucocorticoid activity, which may result in adverse effects such as acne, menstrual changes, drowsiness, breast tenderness, hirsutism, alopecia, insomnia, weight gain, water retention and mood disturbances.

This study aimed to examine the acceptability and perception of postmenopausal women diagnosed with EMPOI, under the age of 45 years, to either MP or MPA in combination with transdermal oestradiol (t-E₂) in the management of their symptoms and development of adverse effects, using a self-reported questionnaire format with matrix rating scales, repeated at intervals of 3, 6 and 12-months from the commencement of the HRT regimen.

Methodology

Patients with a confirmed diagnosis of the menopause secondary to EMPOI (under the age of 45 years), with an intact uterus, were prospectively invited and recruited from two tertiary referral Reproductive Endocrine and Menopause Clinics between April 2013 and August 2015. Subjects fulfilling the inclusion and exclusion criteria (Table 1) were randomised into one of two treatment arms, using a web-based computer randomisation software, GraphPad. Both groups were prescribed 50 mcg/day of t-E₂ in the form of Evorel® patches in conjunction with either cyclical MP (Utrogestan®) 200 mg orally on days 15–26 of a 28-day cycle or, MPA (Provera®) 10 mg orally on days 16–26 of a 28-day cycle, in accordance with the Summary of Product Characteristics of each of the medications.

Table 1.

Inclusion and exclusion criteria.

Inclusion criteria	Exclusion criteria
Females aged between 18 and 45 years	Age <18 or >45 years
Confirmed diagnosis of POI or an EM	Pregnant or lactating females
Willingness to participate	Contraindication to the use of hormonal preparations
No concomitant co-morbidities that would contradict the use of hormonal preparations	Factors present in the medical history: 1. that would contribute to the increased risk of cardiovascular disease 2. known thrombophilia 3. deemed clinically significant by the investigator 4. known porphyria 5. known liver disease 6. known past or suspected breast cancer 7. undiagnosed vaginal bleeding 8. genital tract carcinoma 9. thrombophlebitis
	Smokers
	BMI >35 kg/m²
	Concomitant use of medications that could influence the results, such as anti-hypertensives or anticoagulants
	Known hypersensitivity to any of the active substances or excipients contained within Utrogestan®, Provera® or Evorel patches

BMI: body mass index; EM: early menopause; POI: premature ovarian insufficiency.

Prior to randomisation, the participants were asked to stop their current treatment regimen for a minimum of four weeks, designated a washout period, to enable a baseline assessment to be undertaken.

The questionnaire design was developed using the 12-points described by Burford et al.¹³ The questions were derived from the literature highlighting common symptoms and adverse effects with free text boxes available for additional comments. Face validity was assessed through testing on the target population. Quantitative data were obtained to reduce the Hawthorne effect.¹⁴ The same questionnaire was repeated at 3, 6 and 12-months after the commencement of the HRT regimen.

A matrix scale was used to rank the symptoms or concerns in order of priority with the score 1 signifying the worst symptom or main concern and 10 given to the symptom of least concern. The scores were then grouped together to signify their main symptoms (scores 1–3), moderate symptoms (scores 4–7) and mild symptoms (scores 8–10) for analytical purposes.

A matrix scale was also used to rank the severity and impact of the symptom or concern on the subject’s quality of life, with the score 1 given to signify a low impact and 10 a high impact. The scores were also grouped together for analytical purposes with a score of 1–3 signifying minimal impact, 4–7 signifying moderate impact and 8–10 signifying maximal impact. The data were then presented as a weighted average.

The results were categorised by the treatment arm (t-E₂ + MP or t-E₂ + MPA) and duration of HRT use (3, 6, 12-months from commencement).

Results

Seventy-one subjects were screened. Figure 1 denotes the study algorithm for the response rate categorised by duration from commencement of HRT (baseline, 3, 6 and 12-months) and treatment arm (t-E₂ + MP; t-E₂ + MPA). A total of 190 questionnaires were returned over the 12-month study period.

Figure 1.

Study algorithm. MP: micronised progesterone; MPA: medroxyprogesterone acetate.

An equal proportion of respondents were randomised to each treatment arm (p = 0.89), with an equal distribution across the visits (baseline, 3, 6 and 12-months).

Univariate analysis was performed for age, ethnicity and body mass index (BMI). No statistical difference was demonstrated between the baseline demographic characteristics of the two study populations. The mean age (±standard deviation (SD)) of the patient population was 36.80 ± 6.33 years (age range 19–44 years) (t-E₂ + MP treatment arm 35.75 ± 6.52 years; t-E₂ + MPA treatment arm 37.97 ± 6.02 years; p = 0.17), with a mean BMI of 25.07 ± 4.68 kg/m² (range 17.5–34.9 kg/m²).

52.24% of the respondents were nulliparous (n = 35 (17 randomised to t-E₂ + MP and 18 to t-E₂ + MPA)) with no difference in parity between the two treatment arms (p = 1.00). Nulliparity was demonstrated across all age groups but was more prevalent in women <30 years of age, with women ≥34 years of age being more likely to have at least one child. The mean parity (±SD) for the t-E₂ + MP and t-E₂ + MPA treatment arms was 1.74 (±1.00) and 1.74 (±0.84), respectively.

Four of the respondents were asymptomatic at baseline (5.97%). Infertility was the most commonly reported complaint (n = 51; 76.12%), of which 80.39% (n = 41) reported it to be their main concern, with a weighted average impact score of 8 out of 10. This has been removed from the remainder of the discussion, as this cannot be addressed by the use of HRT alone and is beyond the scope of this paper. Table 2 presents the main concerns (matrix scale score 1–3) of the respondents over the course of the study. The weighted average of the perceived impact of these symptoms on the subjects’ quality of life is illustrated in Figure 2.

Table 2.

The main concerns (matrix scale score 1–3) of the respondents over the course of the study, for both treatment arms grouped together, and separated by the progestogen component.

Symptoms	Baseline		Three months		Six months		Twelve months		P-value
Symptoms	%	n	%	n	%	n	%	n	P-value
Main symptoms reported by the respondents in both treatment arms grouped together
Low energy levels	44.78	30	54	27	55.26	27	48.57	17	0.68
Hot flushes	41.79	28	18	9	15.79	9	14.29	5	<0.05
Low libido	26.87	18	28	14	31.58	14	28.57	10	0.97
Vaginal dryness	22.39	15	10	5	10.53	5	20	7	0.21
Night sweats	19.4	13	10	5	21.05	5	5.71	2	0.14
Low mood	10.45	7	4	2	2.63	2	2.86	1	0.24
Asymptomatic	5.97	4	12	6	10.53	6	8.57	3	0.70
Hair changes	2.99	2	2	1	2.63	1	0	0	–
Sleeping difficulties	0	0	0	0	5.26	0	8.57	3	–
Main symptoms in the t-E₂ + MP treatment arm
Low energy levels	39.39	13	47.83	11	55.56	10	47.37	9	0.73
Hot flushes	42.42	14	21.74	5	22.22	4	15.79	3	0.14
Low libido	33.33	11	26.09	6	27.78	5	31.58	6	0.94
Vaginal dryness	24.24	8	21.74	5	16.67	3	26.32	5	0.90
Night sweats	24.24	8	13.04	3	27.78	5	0	0	–
Low mood	3.03	1	0	0	0	0	0	0	–
Asymptomatic	6.06	2	13.04	3	16.67	3	10.53	2	0.67
Hair changes	3.03	1	4.35	1	5.56	1	0	0	–
Sleeping difficulties	0	0	0	0	0	0	0	0	–
Main symptoms in the t-E₂ + MPA treatment arm
Low energy levels	50	17	59.26	16	55	11	50	8	0.89
Hot flushes	41.18	14	14.81	4	10	2	12.5	2	0.02
Low libido	20.59	7	29.63	8	35	7	25	4	0.68
Vaginal dryness	20.59	7	0	0	5	1	12.5	2	–
Night sweats	14.71	5	7.41	2	15	3	12.5	2	0.82
Low mood	17.65	6	7.41	2	5	1	6.25	1	0.37
Asymptomatic	5.88	2	11.11	3	5	1	6.25	1	0.83
Hair changes	2.94	1	0	0	0	0	0	0	–
Sleeping difficulties	0	0	0	0	10	2	18.75	3	–

MP: micronised progesterone; MPA: medroxyprogesterone acetate; t-E₂: transdermal oestradiol.

Figure 2.

Weighted average of the perceived impact of the reported symptoms on the subjects’ quality of life over the course of the study, for both treatment arms grouped together, and separated by the progestogen component. Minimal impact – score of 1–3; moderate impact – score of 4–7; maximal impact – score of 8–10. MP: micronised progesterone; MPA: medroxyprogesterone acetate.Note. Please refer to the online version of the article to view the figure in colour.

At baseline, prior to randomisation, for both treatment arms combined together, the most commonly reported symptoms were low energy levels (n = 30; 44.78%), vasomotor symptoms (hot flushes: n = 28; 41.79%) and sexual dysfunction (low libido: n = 18; 26.87%). Three months after the commencement of HRT, the three main reported symptoms of all respondents remained as low-energy levels (n = 27; 54.00%), sexual dysfunction (low libido: n = 14; 28.00%) and vasomotor symptoms (hot flushes: n = 9; 18.00%). Six months after the commencement of HRT, the three main reported symptoms of the respondents were low energy levels (n = 27; 55.26%), sexual dysfunction (low libido: n = 14; 31.58%) and vasomotor symptoms (night sweats: n = 5; 21.05%). Twelve months after the commencement of HRT, the three main reported symptoms of the respondents were low energy levels (n = 17; 48.57%), sexual dysfunction (low libido: n = 10; 28.57%) and vasomotor symptoms (hot flushes: n = 5; 14.29%). The frequency of the reported symptoms over the course of the study did not change significantly, except for the initial reduction seen in the proportion of respondents reporting hot flushes (p < 0.05).

An analysis of the main reported symptoms categorised by the treatment arm (Table 2) demonstrated a similar reporting trend over the course of the study, with symptoms of low energy levels, vasomotor symptoms and sexual dysfunction. Urogenital symptoms was the third highest reported symptom within the t-E₂ + MP treatment arm after 12-months duration. Minimal fluctuations was observed in the total number of respondents reporting this symptom throughout the course of the study. The t-E₂ + MPA treatment arm also highlighted sleeping difficulties after 12-months duration.

The weighted average of the perceived impact of the reported symptoms on the individual’s overall quality of life largely improved within the t-E₂ + MP treatment arm in all parameters from baseline (Figure 2). The greatest impact was demonstrated in low mood, changes in hair composition and sleeping difficulties after 12-months duration. In contrast, minimal changes were observed in the t-E₂ + MPA treatment arm after 12-months duration, despite initial improvements seen at 3-months for the symptom’s low mood, changes in hair composition, sleeping difficulties, vasomotor and urogenital symptoms (Figure 2).

A comparison of the reported symptoms between the two treatment arms over the course of the study demonstrated no statistical difference, except for vaginal dryness which was found to be more prevalent within the t-E₂ + MP treatment arm compared to the t-E₂ + MPA arm at 3-months duration (p = 0.02), but this difference was not maintained by 12-months duration (p = 0.42).

Reported adverse effects were documented throughout the study period, the prevalence of which ranged between 57.89 and 87.50%, dependent on the treatment arm that the subjects were randomised to and the duration since commencement of HRT. A comparison between the two treatment arms using Chi-square (Fisher’s exact) demonstrated no statistical difference between the reporting of adverse effects after 3-months (p = 1.00), 6-months (p = 0.47) and 12-months (p = 0.07) duration.

The number of respondents reporting adverse effects reduced, but not significantly, with increased duration of use from 73.91% at 3-months to 57.89% at 12-months duration (p = 0.33) in the t-E₂ + MP treatment arm. In contrast, the number of respondents reporting adverse effects increased, but not significantly, from 76.92% at 3-months to 87.50% at 12-months duration (p = 0.69) in the t-E₂ + MPA treatment arm.

The main reported adverse effects (matrix scale score 1–3) of weight change, gastrointestinal symptom of bloating and psychological effects such as mood swings and irritability remained consistent throughout the study period with increased duration of HRT use when both treatment arms were analysed together (Table 3). Furthermore, the change in the number of respondents reporting each of the adverse effects did not significantly change over the course of the study.

Table 3.

Percentage of respondents reporting the listed adverse effects as their main concern (matrix scale 1–3) over the course of the study, categorised by the progestogen component.

Adverse symptom	Three months		Six months		Twelve months		P-value
Adverse symptom	%	n	%	n	%	n	P-value
Main adverse symptoms categorised by both treatment arms grouped together
Bloating	27.08	13	30.56	11	12.12	4	0.16
Mood swings	25.00	12	33.33	12	27.27	9	0.70
Weight change	22.92	11	27.78	10	19.44	7	0.80
Headache	20.83	10	11.11	4	18.18	6	0.49
Irritability	20.83	10	30.56	11	36.36	12	0.29
Premenstrual like symptoms	12.50	6	22.22	8	18.18	6	0.49
Breast tenderness	12.50	6	13.89	5	18.18	6	0.77
Irregular vaginal bleeding	12.50	6	11.11	4	9.09	3	0.89
Nausea	6.25	3	2.78	1	3.03	1	0.68
Main adverse symptoms in the t-E₂ + MP treatment arm
Bloating	40.91	9	41.18	7	11.76	2	0.10
Weight change	36.36	8	41.18	7	23.53	4	0.53
Breast tenderness	27.27	6	11.76	2	23.53	4	0.49
Mood swings	22.73	5	11.76	2	11.76	2	0.55
Headache	18.18	4	5.88	1	5.88	1	0.35
Irritability	18.18	4	29.41	5	17.65	3	0.63
Premenstrual like symptoms	9.09	2	23.53	4	11.76	2	0.41
Irregular vaginal bleeding	9.09	2	5.88	1	17.65	3	0.51
Nausea	4.55	1	0	0	0	0	–
Main adverse symptoms in the t-E₂ + MPA treatment arm
Mood swings	26.92	7	52.63	10	43.75	7	0.20
Headache	23.08	6	15.79	3	31.25	5	0.56
Irritability	23.08	6	31.58	6	56.25	9	0.09
Premenstrual like symptoms	15.38	4	21.05	4	25.00	4	0.74
Irregular vaginal bleeding	15.38	4	15.79	3	0	0	–
Bloating	15.38	4	21.05	4	12.50	2	0.78
Weight change	11.54	3	15.79	3	18.75	3	0.81
Nausea	7.69	2	5.26	1	6.25	1	0.95
Breast tenderness	0	0	15.79	3	12.50	2	–

MP: micronised progesterone; MPA: medroxyprogesterone acetate; t-E₂: transdermal oestradiol.

All reported adverse effects were reduced (although this did not reach statistical significance) in the t-E₂ + MP treatment arm except for the number of respondents reporting irregular vaginal bleeding which increased after 12-months duration, albeit non-significantly. In contrast, a reported increase in most of the common adverse effects was seen with prolonged MPA use. This, however, did not reach statistical significance. The number of respondents reporting irregular vaginal bleeding and bloating, however, decreased with increased duration of MPA use (Table 3). Furthermore, a significant difference in reported adverse effects was documented between the groups after set periods of time, with a significantly greater proportion of respondents reporting breast tenderness after 3-months duration (p = 0.01), lower numbers reporting mood swings at 6-months duration (p = 0.01) as well as irritability at 12-months duration (p = 0.03) in the t-E₂ + MP treatment arm compared to the t-E₂ + MPA group. No significant difference was documented within the other parameters between the treatment arms.

The weighted average of the perceived impact of the reported adverse effects on the individual’s overall quality of life largely improved by 12-months duration when both treatment arms were analysed together, except for nausea which was reported to be more problematic (Figure 3). In the t-E₂ + MP treatment arm, however, an increase in complaints of both nausea and headaches became more apparent with prolonged use. In the t-E₂ + MPA treatment arm in contrast, mood swings were perceived to gradually worsen with increased duration of use.

Figure 3.

Weighted average of the perceived impact of the reported individual adverse effects on the subjects’ quality of life over the course of the study, categorised by the treatment arm and duration since the commencement of treatment. MP: micronised progesterone; MPA: medroxyprogesterone acetate; t-E₂: transdermal oestradiol.Note. Please refer to the online version of the article to view the figure in colour.

Despite the reported adverse symptoms, 78.86% (n = 97/123) of all responses stated that they would continue to use either HRT preparation outside of a research setting. There was no significant difference in reported satisfaction between the HRT regimens, with 83.33% (n = 50/60) of responses from the t-E₂ + MP treatment arm and 74.60% (n = 47/63) of responses from the t-E₂ + MPA treatment arm stating that they would continue to use the medication outside of a research setting (p = 0.24). Of those, who would overall not continue to use either HRT preparation, 4.17% reported that the medication was not controlling their symptoms, with 50% and 45.83% stating too many adverse effects and inconvenience of the medication as reasons, respectively. When sub-analysed for the progestogen component contained within the regimen, 37.5% of women in the t-E₂ + MP treatment arm compared with 56.25% in the t-E₂ + MPA treatment arm reported the number of adverse effects as being the cause for discontinuation of the medication (p = 0.67).

Discussion

This study addresses the acceptability and personal perception of HRT use by postmenopausal women under the age of 45 years, in the management of their symptoms and development of adverse effects in the context of an EMPOI. Common themes are identified by this study, with young postmenopausal women experiencing the same symptoms as older naturally menopausal women.

The main symptoms reported by the respondents were low energy levels, sexual dysfunction (low libido) and vasomotor type symptoms (hot flushes and night sweats). The frequency of the reported symptoms over the course of the study did not change significantly, except for the initial reduction seen in the proportion of respondents reporting hot flushes (p < 0.05). Furthermore, the perceived impact of these symptoms on the respondent’s quality of life did not change over the course of the study. A number of symptoms were given equal weighting, including low mood, low energy levels, low libido and changes in sleeping patterns. Vasomotor symptoms, despite being reported as a main concern throughout the study duration, were not perceived to detrimentally impact the individual’s overall wellbeing. In contrast, changes within their hair composition were heavily weighted.

The identification of similar patterns of symptoms within the two treatment arms suggests that the estrogen component of the HRT regimen is responsible for the control of them. Testosterone replacement therapy may also have a role in the management of these symptoms. Testosterone replacement was not offered in this study as this would have introduced a further variable in the interpretation of the findings. The primary indication for testosterone replacement is the management of sexual dysfunction with clinical trials demonstrating a positive correlation between testosterone concentrations and its precursors on sexual function.¹⁵ Some studies have also suggested potential enhancement in cognitive function and musculoskeletal health,¹⁶ although this is an area that requires further research.

The reporting of low libido may also be attributed to the associated correlation with infertility with a diagnosis of POI.¹⁶ Liao et al. assessed the psychological wellbeing of women who underwent POI under the age of 40 years. They concluded that a significant proportion of the women with POI experience psychological distress, the degree of which was compounded by age at diagnosis, relationship status and parity.¹⁷ Furthermore, there are many facets to sexual dysfunction, encompassing female sexual interest arousal disorder and discomfort experienced during sexual intercourse. This is supported by the finding of similar numbers of respondents reporting both low libido (approximately 27%) and vaginal dryness (approximately 22%) at baseline, with similar weighting given to both symptoms.

Despite similar symptoms and trends being identified within both treatment arms, the weighted average of the perceived impact of the symptoms on the individual’s overall quality of life largely improved within the t-E₂ + MP treatment arm compared to the t-E₂ + MPA treatment arm. This implies that the progestogen component within the HRT regimen also contributes towards the women’s overall perception of the role of HRT in their health and wellbeing.

A high number of adverse effects were reported in both treatment arms. Broadly, however, a non-significant reduction was observed in the t-E₂ + MP treatment group with increased duration of use, compared to the t-E₂ + MPA treatment arm in which a non-significant increase was demonstrated with increased duration of use.

The most commonly reported adverse effects were bloating, weight change, and the psychological symptoms of mood swings and irritability. A significant difference was seen in reported individual adverse effects between the two groups, with a significantly greater proportion of respondents reporting breast tenderness after 3-months duration but lower numbers reporting psychological symptoms after 6-months duration in the t-E₂ + MP treatment arm compared to the t-E₂ + MPA treatment arm.

The weighted average of the perceived impact of the reported adverse effects on the individual’s overall quality of life, however, largely improved by 12-months duration for both treatment arms as women conditioned themselves to the medication, except for nausea which was found to be more problematic.

The difference in perception of the two treatment regimens is likely to be secondary to the progestogens difference in impact on the androgen receptor, with MPA having a greater affinity for the androgen and glucocorticoid receptors than MP. In contrast, MP more closely resembles naturally occurring progesterone produced by the corpus luteum.

Despite the high number of reported adverse symptoms, more than three quarters of all responses received stated that they would continue to use either HRT regimen outside of a research setting (p = 0.24), implying an overall tolerability and acceptance of the prescribed medication. Satisfaction was lower in the t-E₂ + MPA treatment arm, although this did not reach statistical significance. This correlated to more of the respondents randomised to this arm, reporting adverse effects with increased duration of use. Of those, who would not continue to use the medication, nearly an additional 20% of the respondents in the t-E₂ + MPA treatment arm cited adverse effects as the reason for discontinuation of the medication compared to those randomised to the t-E₂ + MP treatment arm.

Studies incorporating traditional validated questionnaires such as the 36-Item Short-Form Health Survey, Nottingham Health Profile and the condition specific Women’s Health Questionnaire (WHQ) have demonstrated that HRT containing both estrogen and progestogen in the form of MP or MPA do improve the perception of postmenopausal women on their quality of life, as demonstrated in this study. The authors further concluded that MP led to better scores with regards to menstrual problems and cognitive domains of the WHQ when compared to MPA containing HRT.¹⁸ In this study, the reporting of menstrual irregularities was higher within the t-E₂ + MP treatment arm, but the number of women citing psychological symptoms was lower compared to the t-E₂ + MPA treatment arm.

A cross-sectional survey assessing the impact of changing the progestogen component in HRT from MPA to MP on physiological, somatic and vasomotor symptoms, using the Greene Climacteric Scale and WHQ, found that HRT containing MP significantly improved the respondents’ quality of life. This conclusion was based on improved vasomotor symptoms, somatic complaints, anxiety and depressive symptoms, with overall satisfaction reported in 80% of the screened women when compared to HRT containing MPA.¹⁹

This study, however, is limited by its small sample size and high dropout rate. Despite nearly half of the screened subjects not completing the study, overall acceptability amongst those continuing the prescribed medication was high irrespective of the reported adverse effects. This can help support women diagnosed with an EMPOI in whom treatment is advised at least until the natural age of the menopause.

Conclusion

This questionnaire survey has demonstrated that postmenopausal women diagnosed with an EMPOI do perceive an overall improvement in their quality of life with HRT use, despite adverse effects, similar to older naturally menopausal women. The acceptability of both regimens is high, but tolerability of t-E₂ combined with MP appears to be better. Fewer women were noted to report psychological concerns with t-E₂ combined with MP than t-E₂ combined with MPA. Larger studies using validated questionnaires are required in this population to allow a direct comparison with existing studies that have been conducted in older menopausal women.

Footnotes

Acknowledgements

I would like to extend my gratitude to all of the respondents, without whose cooperation I would not have been able to conduct this study.

Author contributions

MM conducted the study. MM and PRS analysed the data. HH formulated the hypothesis and oversaw the manuscript. MM, NP, PRS, MS, LC and HH all checked the manuscript for intellectual content. All authors approved the final submission.

Declaration of conflicting interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: HH is on the Editorial Board for Post Reproductive Health. The other authors declare that there are no conflict of interest.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical approval

Study approval was obtained by the Research and Development Department at King’s College Hospital and ethical approval was granted by the London and GTAC Ethics Committee (REC Number: 12/LO/1957; EudraCT Number: 2012-004511-30) on 16 January 2013. All patients gave informed written consent prior to data collection.

Guarantor

MM.

ORCID iDs

M Mittal

H Hamoda

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