There is a widespread belief that menopause hormone therapy (MHT) represents the most effective modality in the treatment of acute climacteric syndrome. When respecting contraindications, MHT is a highly safe therapy for both acute and subacute climacteric syndromes. If the treatment is started early, the risk/benefit ratio is also positive in prevention of osteoporosis and risk of ischemic cardiac disease. On the other side MHT could be given individually in doses, timing and application way.

Lenzetto® 1.53 mg (Gedeon Richter Plt.) is a transdermal spray-on system (TSS) - estradiol metered-dose transdermal spray (EMDTS). The spray contains 1.7% oestradiol, 8.5% octisalate and ethanol. The volume of one dose is 90 microliters and the adaptor delineating the application area is placed against to the skin of the inner side of an arm or a thigh. A container comprises 56 doses. One to three separate doses (jets) are applied daily without overlapping. The application is always started by one puff, and if the clinical response is not adequate, the dose is increased after one month.The agent is absorbed by the upper layer of stratum corneum and from there released into the organism. The mode of administration allows balanced release with a precise dosage.

To assess the severity of symptoms we used the Menopause Rating Scale (MRS), which had been provided by the patient before the start of the therapy and after 12 and 24 weeks. The study enrolled women at the age of 30 - 65 with the symptoms of acute climacteric syndrome. Postmenopausal status in cases of women with left ovaries was verified by FSH level over 20 IU/l.

A recommended daily allowance of EMDTS was one dose on upper arm at beginning of the study. There was possibility to increase doses after one month in case of insufficient response. Women which still had their uterus had to receive a concomitant gestagen - levonorgestrel intrauterine releasing system or 10 mg dydrogesterone daily orally.

A total of 132 women enrolled for the study in 20 centres. 123 (93.2%) of them completed the study. The average age of the women was 53.8 years (37-65 years).

Women who had used menopause hormone therapy or hormonal contraception within the last six weeks and women with contraindicated hormone replacement therapy (personal history of hormone dependent cancers, thromboembolic disease, cardiovascular disease, acute liver disease, untreated hypertension) were not eligible for the study. Another reason for exclusion was drug abuse (included excessive alcohol intake and smoking).

The body mass index was 26.38 ± 0.91. There were no significant changes during study.

Nine women (6.8%) terminated the study early, five of them for null efficacy, one for facial swelling and pain in lower limbs, and three without giving reasons.

For statistical assessment the Friedman nonparametric test (nonparametric analogue of repeated measures ANOVA) and Wilcoxon signed-rank tests with a Bonferroni correction were used. As a measure of internal consistency of our questionnaire, we used Cronbach’s alpha, which is a measure used to assess the reliability, or internal consistency, of a set of scale or test items. Cronbach’s alpha of 0.70 or higher is considered acceptable in most social science research situations. The statistical significance level was set to 5%. Data were processed using SPSS ver. 23 (SPSS Inc. Chicago, IL) and R software (R Core Team, 2014, version 3.1.2). For assessment of sample size Wilcoxon signed-rank test was used with alpha err prob 0.05, Power 1-beta = 0.8 and parent distribution min ARE. For the effect size dz = 0.3 we calculated n = 120.

There was a statistically significant decrease of the MRS score with p < 0.001. In all groups, there was a significant reduction between the first and the second visit, the second and the third visit, and the first and third visit, respectively, with p < 0.001; the only exception was the effect of treatment on bladder problems between the second and the third visit, which was decreased (means: 0.46, 0.28, 0.22), but the decrease was not statistically significant (p = 0.035, alpha = 0.017).

There was an average improvement by 66.2% between the first and third visit; the most significant improvement was observed in the area of “hot flushes and sweating”, “sexual problems”, and “heart discomfort” (75.4%, 73.2%, and 70.4%, respectively). The lowest improvement was observed for MRS components “bladder problems”, “depressive mood”, and “anxiety” (51.8%, 58.4%, and 59.4%, respectively).

The most significant improvement was observed in patients with initial moderate climacteric syndrome (70.9%).

The only significant risk presented by MHT administration for common population is thromboembolic disease, but it is not increased when the drug is not applied orally. The advantage of transdermal (patches, spray), percutaneous (gels) and subcutaneous (biodegradable implants) applications lies in providing a stable blood level of the drug compared to oral administration, which shows daily fluctuations. The first-pass effect is missed.

Transdermal MHT shows the same efficacy in the treatment of vasomotoric problems and urogenital atrophy as the oral form and a similar beneficial effect on bone density.

This study confirms that application of a EMDTS offers an novel treatment option for climacteric symptoms.The study has shown that investigators have not adequately used the flexibility of dosing of this spray. The excellent tolerability is also a very important factor for clinical practice.