A 10-year follow-up of postmenopausal women on long-term continuous combined hormone replacement therapy: Update of safety and quality-of-life findings.
OBJECTIVE
To assess the safety and health-related quality of life (HRQOL) of continuous combined hormone replacement therapy (ccHRT) with estradiol valerate/medroxyprogesterone acetate (E(2)V/MPA) over nine years and at follow-up one year after discontinuation.


METHODS
A total of 419 women were randomized to one of four treatments: once-daily 1 mg E2V/2.5 mg MPA (1 + 2.5 group); 1 mg E2V/5 mg MPA daily (1 + 5 group); 2 mg E2V/2.5 mg MPA daily (2 + 2.5 group); 2 mg E2V/5 mg MPA daily (2 + 5 group) (Indivina, Orion Pharma). For the last six months, all received the 1 + 2.5 dosage. The 2 + 2.5 dosage was discontinued at the end of year 7. A total of 198 women continued after year 7.


RESULTS
Annualized percentage rates for cardiovascular events [corrected] and endometrial cancers [corrected] were below national rates for Finland and those reported for the Women's Health Initiative. There were no serious events with the 1 + 2.5 dosage or after ccHRT discontinuation. Climacteric symptoms remained significantly below baseline values after dosage reduction; some symptoms recurred after discontinuation of ccHRT. HRQOL ratings improved with ccHRT, irrespective of dosage, including depressed mood, anxiety, health perception and sexual interest. Scores on a scale assessing daily functioning and enjoyment (Q-LES-Q) improved from year 7 to year 9. They deteriorated during follow-up in women not continuing ccHRT.


CONCLUSIONS
Lower dosages of HRT were as effective as higher doses in improving climacteric symptoms and HRQOL ratings and had fewer safety concerns. Following discontinuation of ccHRT, patient satisfaction was variable, with 15% electing to continue or restart HRT and 7% resuming at follow-up. This supports the need for an individualized approach to therapy recommendations.
Heikkinen
Jorma
J
The Deaconness Institute of Oulu, Isokatu, Oulu, Finland.
Vaheri
Raija
R
Timonen
Ulla
U
D001943:Breast Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D016889:Endometrial Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005387:Finland; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy / Q000009:adverse effects / Q000523:psychology; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects* / Q000502:physiology; D011788:Quality of Life; D020521:Stroke / Q000139:chemically induced / Q000453:epidemiology; D016896:Treatment Outcome
D004966:Estrogens, Conjugated (USP); D004958:Estradiol; D017258:Medroxyprogesterone Acetate