Hi there all
There have been numerous discussions on different threads about hair loss on HRT but in particular about Vagifem with members (rightly) quoting some information from one of the commerical websites suggesting that this was a side effect.
I decided to write to Novo nordisk about this as it seemed to be at odds with the information here in UK on our own medicines database.
Rather than this response getting buried in one of these threads I thought members might be interested to read their response (they also sent some tables but think they don't reproduce well on this forum software although you can see the data), so I have reproduced it in full.
START OF QUOTE "Dear
Thank you for your recent enquiry on the following subject:
Vagifem® (estradiol vaginal tablet) 10 mcg; information on www.vagifem.com website regarding hair lossThank you for the information that patients taking Vagifem® have reported hair loss. We do not have enough information make any comment on whether there is a causal relationship between the hair loss and our product in these individual patients.
The
www.vagifem.com website was created by our colleagues in the USA for consumers in that country and is not intended for use in the UK. You will notice that the Prescribing Information displayed on the website is from the USA.
As you may know, the regulations on the marketing of medicines in the USA are very different from those in the UK and Europe. US pharmaceutical companies can promote medicines directly to the public which is, of course, not permitted in the UK. The differing FDA requirements on the safety information that they provide when marketing their products may account for the difference in the information found on this USA website from that which we provide in the Vagifem® Summary of Product Characteristics and (SmPC) in the UK.
I see that the
www.vagifem.com website includes the following:
‘
What are the possible side effects of Vagifem®?'
Vagifem® is only used in the vagina; however, the risks associated with oral estrogens should be taken into account. The most commonly reported side effects of Vagifem® include: headache, breast pain, irregular vaginal bleeding or spotting, stomach/abdominal cramps, bloating, nausea and vomiting, hair loss, fluid retention, and vaginal yeast infection.'
As you have correctly observed, the Vagifem® SmPC in the UK does not list hair loss as a side effect. The clinical trials and post-marketing surveillance of this product did not identify hair loss as a recognised side effect. Hair loss is a known side effect of oral oestrogen products and, as you have pointed out, can sometimes occur naturally due to hormonal changes during the menopause.
The intended meaning of the information on the USA website seems to be that the known effects of oral oestrogen, including hair loss, should be considered in relation to this product. Unfortunately, the way it is written suggests that hair loss is a recognised side effect of Vagifem®, which is not the case.
I hope the following data on the adverse effects of Vagifem® 10mcg reported from our clinical trials will be helpful.
Clinical safetySimon et al evaluated the long-term efficacy and safety of Vagifem® 10 mcg in a 52-week, multicentre, double-blinded, randomized, parallel-group, placebo-controlled study . Three hundred and nine postmenopausal women, with moderate to severe urogenital symptoms, were randomized to Vagifem® 10 mcg (n=205) or placebo (n=104). Treatment regimen was to insert one tablet vaginally daily for 14 days, followed by one tablet twice weekly. The most common adverse events reported for Vagifem® 10 mcg were vulvovaginal mycotic infection, back pain and vulvovaginal pruritus whereas placebo-treated patients reported headaches and vaginal discharge.
A 12-week, randomized, placebo-controlled, double-blind trial was conducted by Bachmann et al in 230 postmenopausal women complaining of moderate to severe atrophic vaginitis . This study compared the efficacy and safety of Vagifem® 10 mcg and 25 mcg to placebo. At the end of the 12-week study, the women were switched to an open-label extension and treated with Vagifem® 25 mcg for 52 weeks. The most commonly reported adverse events are reported in Table 1.
Table 1. Common Treatment-emergent adverse events Vagifem® 10 mcg Vagifem® 25 mcg Placebo
Headache 3% 9% 6%
Back pain 0 7% 6%
Abdominal pain 5% 7% 4%
Moniliasis genital 0 5% 2%
Upper respiratory infection 7% 5% 4%
Vaginitis 4% 3% 6%
Vaginal discomfort 5% 3% 0
One death and three serious adverse events were reported during the study, however none of these events were considered related to study drug.
Overall, clinical studies of Vagifem® 10mcg have found that oestrogen-related adverse effects occur at a low rate, similar to placebo, but if they occur, this is usually only at the beginning of treatment.
Endometrial SafetyA 52-week, multicentre, single-arm, open-label clinical trial was conducted in 336 postmenopausal women, with moderate to severe symptoms of urogenital atrophy, to assess the endometrial safety of Vagifem® 10 mcg .
Vagifem® 10 mcg was given once daily for the first two weeks followed by twice weekly maintenance therapy. By the end of week 52, 284 biopsies were performed. Data from this study was combined with data from 205 patients receiving active treatment in the above efficacy study by Simon to give a pooled analysis of endometrial safety for 541 women who had received 52 weeks of treatment with Vagifem® 10mcg .
Table 2. Endometrial Biopsy Results with Vagifem® 10 mcg Treatment After 52 Weeks Baseline Week 52
Total Number of Endometrial Biopsies 537 443
No tissue 23 (4.3%) 51 (11.5%)
Insufficient Tissue 169 (31.5%) 126 (28.4%)
Atrophic or Inactive Endometrium 331 (61.6%) 258 (58.2%)
Weakly Proliferative 2 (0.4%) 1 (0.2%)
Complex Hyperplasia without atypia 0 0
Endometrial Carcinoma 0 1 (0.2%)
Polyps 9 (1.7%) 5 (1.1%)
Other 3 (0.6%) 1(0.2%)
One patient was found to have endometrioid adenocarcinoma at the end of the study. Because the screening biopsy had revealed 'no tissue' but was not repeated, it is uncertain whether the carcinoma was pre-existing at baseline. This patient had a previous history of treatment with an unopposed systemic oestrogen and methyltestosterone combination for two years. One case of complex hyperplasia without atypia was diagnosed in a patient who discontinued the study after only 9 days of trial drug exposure.
Endometrial thickness was measured by transvaginal ultrasounds in these studies. Mean endometrial thickness was 2.14 mm at baseline and remained unchanged at the end of 52 weeks of treatment.
In summary, clinical studies of Vagifem® 10mcg have not shown any serious adverse events which were considered to be due to the study drug. Studies of patients taking Vagifem® 10mcg for one year have shown no increased risk of endometrial stimulation. As a general rule, oestrogen therapy should not be prescribed for longer than one year without a physical and gynaecological examination being performed. The addition of a progestagen is not recommended with local treatment with Vagifem® 10mcg. Please see section 4.8 Undesirable effects of the Vagifem® Summary of Product Characteristics for further information.
I hope this information is of assistance, but if we can be of any further help, please do not hesitate to contact us again.
Yours sincerely,
Jackie Gilbart
Medical Information Specialist
on behalf of the Medical Affairs team
Enc.
References Simon J, Obstetrics and Gynecology 2008; 112:1053-60
Bachman,G. et al, Obstetrics & Gynecology 2008;111:67-76
Ulrich LS, Climacteric, 2010; 13: 228-37
Simon J, Obstetrics and Gynecology, 2010; 116:876-83
Vagifem Summary of Product Characteristics "
END OF QUOTEThey also sent me copies of these papers listed above.
Anyone who feels they have experienced side effects not listed should report to the MHRA under the yellow card scheme or get in touch with the company directly and it will be sent to the safety department, although post-marketing anecdotal evidence does not have the same status as trials results - but is still helpful to report.
I hope this information is of interest.
Hurdity x
Author
Topic: Vagifem, hairloss and safety - response from Novo nordisk (Read 4134 times)