Long-term medical management of endometriosis with dienogest and with a gonadotropin-releasing hormone agonist and add-back hormone therapy.

Endometriosis can recur after either surgical or medical therapy. Long-term medical therapy is implemented to treat symptoms or prevent recurrence. Dienogest and gonadotropin-releasing hormone (GnRH) analogues with hormone add-back therapy seem to be equally effective for long-term treatment of pain symptoms associated with endometriosis. There is insufficient evidence to support the superiority of one therapy over the other. However, add-back hormone therapy (HT) is recommended for patients using GnRH agonists. The treatment selection depends on therapeutic effectiveness, tolerability, drug cost, the physician's experience, and expected patient compliance.

Norethindrone acetate or dienogest for the treatment of symptomatic endometriosis: a before and after study.

OBJECTIVE: To assess the proportion of patients satisfied with their treatment before and after a systematic change from norethindrone acetate to dienogest as the first-line progestin for symptomatic endometriosis. DESIGN: Before and after study. SETTING: Academic department. PATIENT(S): The last 90 new consecutive endometriosis patients in whom norethindrone acetate was used, and the first 90 new consecutive endometriosis patients in whom dienogest was used. INTERVENTION(S): Norethindrone acetate at the oral dose of 2.5 mg once a day until June 6, 2013, then dienogest at the oral dose of 2 mg once a day thereafter. MAIN OUTCOME MEASURE(S): Degree of satisfaction with treatment after 6 months of progestin therapy and assessment of any variations in pain symptoms, psychological status, sexual function, or health-related quality of life associated with the introduction of dienogest. RESULT(S): The proportion of satisfied plus very satisfied women after 6 months of treatment was 71% in the "before" period (norethindrone acetate) and 72% in the "after" period (dienogest). The implementation of dienogest was not associated with statistically significant ameliorations in overall pain relief, psychological status, sexual functioning, or health-related quality of life. Treatment was well tolerated by 58% of norethindrone acetate users compared with 80% of dienogest users. After dienogest implementation, the absolute risk reduction in the occurrence of any side effect was 13.9% (95% confidence interval, 0.8%-28.6%). CONCLUSION(S): Considering the large difference in the cost of the two drugs, dienogest should be suggested selectively in women who do not tolerate norethindrone acetate.

Cost-effectiveness analysis in the treatment of heavy menstrual bleeding in Spain.

OBJECTIVE: To compare the effectiveness and costs associated with first-line medical treatments for chronic heavy menstrual bleeding (HMB) in Spain. STUDY DESIGN: A cost-effectiveness analysis was conducted comparing the levonorgestrel-releasing intrauterine system (LNG-IUS) with the estradiol valerate/dienogest multiphase oral contraceptive (E2V/DNG), combined oral contraceptives (COC) and progestins (PROG). Study patients were fertile women diagnosed with HMB who initially wished to remain fertile. A Markov model based on reported clinical data and the opinion of a panel of experts was used. The time horizon of the analysis was 5 years. The analysis was conducted from the perspective of the Spanish National Health System (NHS), discounting both costs (€ 2013) and future effects at an annual rate of 3%. One-way sensitivity analyses and probabilistic sensitivity analysis were performed to test the robustness of the results. RESULTS: In the analysis at 5 years, the LNG-IUS was associated with a gain of 0.67, 2.22, and 3.53 symptoms free months (SFM) compared with E2V/DNG, COC and PROG, respectively. LNG-IUS contributed more quality-adjusted life months (QALM) than the other treatment alternatives (+1.74 vs. E2V/DNG, +3.33 vs. COC +3.53 vs. PROG). First-line LNG-IUS treatment resulted in savings of € 583, € 988, and € 1891 vs. E2V/DNG, COC and PROG, respectively. These cost benefits, coupled with the greater clinical benefits in terms of SFM and QALM, show that LNG-IUS is the dominant option (less costly and more effective). CONCLUSION: LNG-IUS is the medical treatment of choice and cost-saving option for the control of HMB in Spain.

Estradiol valerate/dienogest: a novel combined oral contraceptive.

BACKGROUND: Estradiol valerate/dienogest (E2V/DNG) is a combined oral contraceptive (COC) with 2 new hormonal entities and a unique 4-phasic dosing regimen indicated for women to prevent pregnancy. OBJECTIVE: The purpose of this article is to review the pharmacology, pharmacokinetics, clinical efficacy, tolerability, and cost of E2V/DNG. METHODS: MEDLINE (1966-June 2011) and EMBASE (1966-June 2011) were searched for original research and review articles published in the English language using the terms Natazia or Qlaira or estradiol valerate and dienogest. The reference lists of identified articles were reviewed for additional pertinent publications. Abstracts from the 2005 to 2011 American Society of Reproductive Medicine and American College of Obstetricians and Gynecologists meetings were searched using the same terms. RESULTS: The search provided 56 articles that addressed the pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, and tolerability of E2V/DNG in women of reproductive age. Articles reporting efficacy or tolerability in the setting of menopause were excluded. The initial efficacy of E2V/DNG on ovulation inhibition was investigated in 2 prospective, randomized, open-label, Phase II dose-finding studies. The dose that was approved by the Food and Drug Administration resulted in 3.13% of women ovulating in the second cycle of treatment (90% CI, 0.2%-6.05%). Rate of pregnancy prevention with this agent was reported with a Pearl Index ranging from 0.73 to 1.27 (unadjusted) to 0.34 to 0.72 (adjusted for method failure only). The mean duration of withdrawal bleeding was 4.3 days (range, 4.0-4.6 days) among 2266 women receiving 13 treatment cycles. Adverse events reported in >1% of patients included abdominal pain, acne, breast pain, dysmenorrhea, emotional lability, headache, nausea, and weight increase. CONCLUSIONS: Estradiol valerate/dienogest is a new contraceptive formulation. It offers efficacy, tolerability, and an acceptable safety profile with a potentially better bleeding pattern than levonorgestrel-containing COCs. This COC may be especially useful for older women of reproductive age who are adherent to therapy and looking for shorter and/or lighter menstrual cycles. Studies will need to be performed to determine whether clinically significant differences in outcomes exist among E2V/DNG and other available COCs.

Estradiol valerate/dienogest: a novel oral contraceptive.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of the new oral contraceptive estradiol valerate/dienogest. DATA SOURCES: Searches of PubMed (1966-July 2011) and International Pharmaceutical Abstracts (1970-July 2011) were conducted using the key words estradiol valerate, dienogest, Natazia, and Qlaira. Bibliographies of retrieved articles were reviewed to identify additional references. STUDY SELECTION AND DATA EXTRACTION: All identified studies published in English and involving efficacy and safety of estradiol valerate/dienogest as an oral contraceptive were reviewed. DATA SYNTHESIS: Estradiol valerate/dienogest is a 4-phasic oral contraceptive approved for the prevention of pregnancy. The 4-phasic design allows for acceptable cycle control with this hormonal combination. In efficacy trials of estradiol valerate/dienogest in women aged 18-35 years, the Pearl Index ranged from 0.40 to 1.64, a range comparable to that of other combination oral contraceptives. The safety profile was also similar to that of other oral contraceptives, with headache, metrorrhagia, breast tenderness, nausea or vomiting, acne, and weight gain reported as the most common adverse effects. Menstrual bleeding patterns and cycle control with estradiol valerate/dienogest were comparable to those of a monophasic oral contraceptive containing ethinyl estradiol/levonorgestrel. Estradiol valerate/dienogest differs from other oral contraceptives in that it necessitates more stringent dosing guidelines for maximum contraceptive efficacy. New starts should be on the first day of menses only, and a back-up method of contraception is required for the first 9 days, as compared to 7 days with other oral contraceptives. Back-up contraception is usually required for any pill taken more than 12 hours later than scheduled. CONCLUSIONS: Estradiol valerate/dienogest is an effective oral contraceptive. Because it has more stringent start times and requires a longer duration of backup contraception and stricter adherence, estradiol valerate/dienogest should be reserved for patients who are intolerant of other combination oral contraceptives.

Androgen therapy for anaemia of chronic renal failure. Indications in the erythropoietin era.

The high cost of recombinant human erythropoietin has led us to consider the existing indications for androgen treatment of anaemia in patients with chronic renal failure. In the present work, we have tried to identify those patients on haemodialysis for whom androgens could constitute a therapeutic alternative. The evolution of haemoglobin concentration was analysed in 84 patients (67 males and 17 females) treated with a cycle of nandrolone decanoate (200 mg per week given intramuscularly, for six months). In the total group of patients, haemoglobin rose from 69 g/L to 87 g/L (p < 0.01). The increment in haemoglobin was not related to sex, basal haemoglobin, primary renal disease, or dose of nandrolone decanoate corrected by body weight. However, we observed a relationship between this increment in haemoglobin and patient age. Haemoglobin increased by 8 g/L in patients younger than 46 years (n = 29), by 18 g/L in patients aged between 46 and 55 years (n = 28), and by 27 g/L in patients older than 55 years (n = 27) (p < 0.01 between groups). In the last group, haemoglobin concentration at the end of androgen treatment was 101 +/- 16 g/L. The haemoglobin level reached during androgen treatment was maintained for over a year after androgen withdrawal in 55% of the responder patients. A reversible rise in the serum concentration of triglycerides was the main side-effect observed. Nandrolone decanoate therapy was not associated with hepatotoxicity or an increase in blood pressure. Voice change and mild hirsutism were observed in most of the women receiving nandrolone decanoate, and these secondary effects constitute a real disadvantage to its use in females. In conclusion, our results showed that androgens are a useful alternative in the treatment of anaemia in male haemodialysis patients older than 55 years. Furthermore, the response obtained was similar to that observed with erythropoietin, but at a lower cost.