Lenzetto Adverse Reactions

In a 12-week, randomised, placebo-controlled trial of Lenzetto in 454 women, 80-90% of women who were randomised to active substance received at least 70 days of therapy and 75-85% of the women who were randomised to placebo received at least 70 days of therapy.
The adverse events are listed by organ class and frequency according to MedDRA frequency convention: Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000). (See Table 2.)

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From post-marketing surveillance additionally, the following adverse events have been reported: Skin and subcutaneous tissue disorders: Alopecia; Chloasma; Skin discolouration.
Breast cancer risk: An up to 2-fold increased risk of having breast cancer diagnosed is reported in women taking combined estrogen-progestagen therapy for more than 5 years.
The increased risk in users of estrogen-only therapy is lower than that seen in users of estrogen-progestagen combinations.
The level of risk is dependent on the duration of use (see Precautions).
Absolute risk estimations based on results of the largest randomised placebo-controlled trial (WHI-study) and the largest meta-analysis of prospective epidemiological studies are presented. (See Tables 3, 4 and 5.)

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Endometrial cancer risk: Postmenopausal women with a uterus: The endometrial cancer risk is about 5 in every 1,000 women with a uterus not using HRT.
In women with a uterus, use of estrogen-only HRT is not recommended because it increases the risk of endometrial cancer (see Precautions).
Depending on the duration of estrogen-only use and estrogen dose, the increase in risk of endometrial cancer in epidemiology studies varied from between 5 and 55 extra cases diagnosed in every 1000 women between the ages of 50 and 65.
Adding a progestagen to estrogen-only therapy for at least 12 days per cycle can prevent this increased risk. In the Million Women Study the use of five years of combined (sequential or continuous) HRT did not increase risk of endometrial cancer (RR of 1.0 (0.8-1.2)).
Ovarian cancer: Use of estrogen-only or combined estrogen-progestagen HRT has been associated with a slightly increased risk of having ovarian cancer diagnosed (see Precautions).
A meta-analysis from 52 epidemiological studies reported an increased risk of ovarian cancer in women currently using HRT compared to women who have never used HRT (RR 1.43, 95% CI 1.31-1.56). For women aged 50 to 54 years taking 5 years of HRT, this results in about 1 extra case per 2,000 users. In women aged 50 to 54 who are not taking HRT, about 2 women in 2,000 will be diagnosed with ovarian cancer over a 5-year period.
Risk of venous thromboembolism: HRT is associated with a 1.3-3-fold increased relative risk of developing venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism. The occurrence of such an event is more likely in the first year of using HT (see Precautions). Results of the WHI studies are presented: (see Table 6.)

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Risk of coronary artery disease: The risk of coronary artery disease is slightly increased in users of combined estrogen-progestagen HRT over the age of 60 (see Precautions).
Risk of ischaemic stroke: The use of estrogen-only and estrogen + progestagen therapy is associated with an up to 1.5-fold increased relative risk of ischaemic stroke. The risk of haemorrhagic stroke is not increased during use of HRT.
This relative risk is not dependent on age or on duration of use, but as the baseline risk is strongly age-dependent, the overall risk of stroke in women who use HRT will increase with age see Precautions. (See Table 7.)

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The following additional adverse reactions have also been reported with estrogen and/or progestin therapy: angioedema, anaphylactoid/anaphylactic reactions, glucose intolerance, mental depression, mood disturbances, irritability, exacerbation of chorea, exacerbation of epilepsy, dementia (see Precautions), exacerbation of asthma, cholestatic jaundice, increased incidence of gallbladder disease, pancreatitis, enlargement of hepatic haemangiomas, chloasma or melasma, that may persist when drug is discontinued; erythema multiforme, haemorrhagic eruption, loss of scalp hair, arthralgias, galactorrhoea, fibrocystic breast changes, increase in size of uterine leiomyomata, change in amount of cervical secretion, changes in cervical ectropion, vaginal candidiasis, hypocalcaemia (pre-existing condition).
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.