New Drugs: Australian Prescriber

ome of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer’s approved product information, a drug information centre or some other appropriate source.


Aust Prescr 2015;38:138-42

Approved indication: endometriosis
Visanne (Bayer)
2 mg tablets
Australian Medicines Handbook section 17.4

Endometriosis is a common condition, affecting up to 10% of women. It occurs when endometrial cells proliferate outside the uterus, for example on the ovaries or in the peritoneum. It is associated with symptoms such as chronic pelvic pain, and pain during menstruation and sexual intercourse.

Drug treatments for endometriosis aim to suppress ovarian function and include androgens (e.g. danazol), gonadotropin-releasing hormone agonists (e.g. goserelin) and progestogens.

Dienogest is a progestogen-only hormone preparation for the treatment of endometriosis. It works by suppressing oestradiol production and preventing the growth of the endometrium. Dienogest is already available in Australia in combination with an oestradiol in some oral contraceptive pills (Aust Prescr 2007;30:50-5, Aust Prescr 2015:38;6-11).

In an open-label, dose-finding trial of 68 women, daily dienogest 2 mg or 4 mg significantly reduced the severity of endometriosis, scored by laproscopic examination at baseline and 24 weeks later. It also decreased rates of pain during sexual intercourse from 52% to around 6%. Rates of premenstrual pain, dysmenorrhoea and diffuse pelvic pain were also reduced. The trial concluded that dienogest 2 mg once a day was the lowest effective dose.1 (A 1 mg dose of dienogest was also included in the trial, but randomisation was stopped prematurely due to irregular bleeding in all four patients receiving this dose.)

In a 12-week placebo-controlled trial involving 198 women, daily dienogest 2 mg significantly reduced pelvic pain compared with placebo on a 100-mm visual analogue scale (by 27.4 mm vs 15.1 mm).2 The clinical significance of this difference was unclear. In a 52-week open-label extension of this study, 87 women continued dienogest and 81 who had taken placebo started the drug. Treatment continued for up to 52 weeks. The mean pain score declined from 27.89 mm to 9.72 mm in previously treated patients, and from 40.73 mm to 13.49 mm in those who switched from placebo. At the end of treatment the mean score for all patients was 11.52 mm.3 However, approximately a quarter of the women still used analgesia for their symptoms. A group of 34 women were followed up for 24 weeks after treatment finished. Their mean pain score increased slightly to 14.56 mm.3

Dienogest has been compared to the gonadotropin-releasing hormone agonist leuprolide (leuprorelide) in an open-label non-inferiority study of 252 women. After 24 weeks of treatment, pelvic pain – assessed by a 100-mm visual analogue score – had reduced from 60.2 mm to 12.7 mm with daily dienogest 2 mg and from 57.9 mm to 11.9 mm with leuprorelide (3.75 mg by depot intramuscular injection every four weeks). The trial concluded that dienogest was non-inferior to leuprorelide.4 (A non-inferiority margin of 15 mm was pre-specified on a 100-mm visual analogue scale.)

Similarly dienogest was found to be as effective as buserelin (given intranasally), another gonadotropin-releasing hormone agonist. However, dienogest was associated with more vaginal bleeding than the comparator.5

In a safety cohort of 727 women, the most frequently reported adverse effects with dienogest were headache (9%), acne (5.1%), nausea (4.2%), weight gain (3.6%), breast tenderness (3.3%), depressed mood (3.0%) and flatulence (3.0%). As severe depression has been reported with dienogest,4 patients with a history of depression should be monitored closely.

Changes in menstrual bleeding patterns were common in the trials, but did not usually lead to discontinuation. After 9–12 months, bleeding was normal in 22.8% of women but had stopped (28.2%), become infrequent (24.2%), frequent (2.7%), irregular (21.5%) or prolonged (4%) in others.

Dienogest is contraindicated in undiagnosed vaginal bleeding and during pregnancy and lactation. Although ovulation is inhibited in most patients, dienogest is not a contraceptive and use of a non-hormonal method is recommended while taking dienogest. The menstrual cycle resumes within two months of stopping the drug.

Dienogest should not be given to patients with an active thromboembolic disorder or a history of cardiovascular disease. The risk of cardiovascular events is associated with older age, hypertension and smoking. Diabetes and severe hepatic disease, a history of liver tumours or sex-hormone dependent malignancies are contraindications to dienogest. If cholestatic jaundice or pruritis develops, dienogest should be stopped.

It was not clear from the trials if dienogest affects bone mineral density. If treatment is continued for longer than six months, consider monitoring bone mineral density.

After oral administration, dienogest is rapidly absorbed with peak serum concentrations being reached after approximately 1.5 hours. It is completely metabolised, mainly by cytochrome P450 (CYP) 3A4, and metabolites are rapidly excreted in the urine and faeces.

Inducers of CYP3A4, such as rifampicin or St John’s wort, may decrease plasma concentrations of dienogest, whereas CYP3A4 inhibitors, such as fluoxetine, ketoconazole or erythromycin, may increase dienogest concentrations.

Dienogest can be started on any day of the menstrual cycle. It should be taken every day without interruption. If a tablet is missed, the next one should be taken as soon as possible and dosing continued as normal the next day. As with the contraceptive pill, vomiting and diarrhoea can reduce the efficacy of dienogest.

Dienogest reduces the pain associated with endometriosis and is comparable to gonadotropin-releasing hormone agonists. However, some women may still need analgesia for their pelvic pain.

T-Score manufacturer provided the AusPAR and/or the product information


  1. Köhler G, Faustmann TA, Gerlinger C, Seitz C, Mueck AO.A dose-ranging study to determine the efficacy and safety of 1, 2 and 4 mg of dienogest daily for endometriosis.Int J Gynecol Obstet 2010;108:21-5.
  2. Strowitzki T, Faustmann T, Gerlinger C, Seitz C. Dienogestin the treatment of endometriosis-associated pelvic pain:a 12-week, randomized, double-blind, placebo-controlledstudy. Eur J Obstet Gynecol Reprod Biol 2010;151:193-8.
  3. Petraglia F, Hornung D, Seitz C, Faustmann T, Gerlinger C,Luisi S, et al. Reduced pelvic pain in women with endometriosis: efficacy of long-term dienogest treatment.Arch Gynecol Obstet 2012;285:167-73.
  4. Strowitzki T, Marr J, Gerlinger C, Faustmann T, Seitz C.Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial. Human Reprod 2010;25:633-41.
  5. Harada T, Momoeda M, Taketani Y, Takeshi A, Fukunaga M,Hagino H, et al. Dienogest is as effective as intranasal buserelin acetate for the relief of pain symptoms associated with endometriosis – a randomized, double-blind,multicenter, controlled trial. Fertil Steril 2009;91:675-81.

Crocus sativus L. (azafrán) prometedor para tratamiento de síndrome premenstrual

Crocus sativus L. (azafrán) prometedor para tratamiento de síndrome premenstrual

En la medicina persa tradicional el azafrán es usado para tratamiento de dolencias de estómago y depresión. Estos investigadores iraníes llevaron a cabo un estudio randomizado, doble ciego y placebo controlado para determinar si el azafrán (Crocus sativus L.) podría aliviar síntomas de síndrome premenstrual (PMS). Las participantes eran mujeres de 20-45 años de edad con ciclos menstruales regulares y el antecedente de síntomas PMS en al menos los últimos 6 meses. Ellas fueron asignadas al azar para recibir azafrán cápsulas de 15 mg dos veces al día o un placebo durante dos ciclos menstruales.

Ellos encontraron que entre 50 sujetos hubo mejoría estadísticamente significativa en mujeres que recibían azafrán, medido por el Reporte Diario de Síntomas y la Escala Hamilton de Evaluación de Depresión, comparado con el placebo. No hubo eventos adversos estadísticamente significativos. Los autores concluyeron que sus resultados indican la eficacia y tolerabilidad de C. sativus L. en el tratamiento de PMS y muy bien pueden confirmar la aplicación de azafrán como una alternativa de tratamiento para PMS. Es necesaria mayor investigación.

Son necesarios estudios más grandes y de mayor duración pero, mientras tanto, parece no existir razón para probarlo si el costo es razonable para el paciente.

BJOG 115:515-519, Marzo 2008. © 2008 Royal College of Obstetricians and Gynaecologists.

Crocus sativus L. (azafrán) en el tratamiento de síndrome premenstrual: un estudio doble ciego, randomizado y placebo controlado, M Agha-Hossein, L Kashani, A Aleyaseen, A Ghoreishi, H Rahmanpour, AR Zarrinara, S Akhondzadeh. Correspondencia a Profesor Akhondzadeh:

Categoría X. Female Genital System, Breast. Palabras claves: Crocus sativus L., azafrán, síndrome premenstrual, Hamilton Depression Rating Scale, estudio randomizado controlado

Sinopsis editado por Dr Linda French, Toledo, Ohio. Colocado en Global Family Doctor marzo 2008.
Traducido por Dra. Patricia Mitchell, Universidad de Oriente, Venezuela, Febrero 2008.

Ginecologia: Desordenes Cervicales

Atlas de procedimientos en ginecologia oncologica

Atlas of Procedures in Gynecologic Oncology
By Douglas A. Levine, Richard R. Barakat, William J. Hoskins

  • Publisher: Informa Healthcare
  • Number Of Pages: 288
  • Publication Date: 2003-05-01
  • ISBN-10 / ASIN: 184184196X
  • ISBN-13 / EAN: 9781841841960
  • Binding: DVD

Book Description:

Expert practitioners at one of the world’s leading cancer centers have here collaborated on a practical guide to the procedures involved in gynecologic oncology. They explain the latest developments in both open and minimally invasive surgery. All the requisite procedures are comprehensively profiled, including cytoreduction, pelvic extenteration, brachytherapy and other treatments. The procedures are explained step-by-step and fully illustrated, with 800 color photographs. An accompanying CD-ROM provides over one hour of video clips with spoken commentary. Atlas of Procedures in Gynecologic Oncology is indispensable for clinicians and students in oncology and gynecology.


Histerectomía total versus subtotal para las enfermedades ginecológicas benignas (Revisión Cochrane traducida)

Histerectomía total versus subtotal para las enfermedades ginecológicas benignas (Revisión Cochrane traducida)

Lethaby A, Ivanova V, Johnson NP

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Fecha de la modificación significativa más reciente: 03 de febrero de 2006. Las revisiones Cochrane se revisan regularmente y se actualizan si es necesario.


Cuando es necesaria la histerectomía abdominal para las enfermedades no cancerosas, se puede extraer el útero solo (histerectomía subtotal) o el útero y el cuello uterino (histerectomía total). Algunas personas han sugerido que la conservación del cuello uterino (histerectomía subtotal) disminuiría el riesgo de dificultades sexuales o problemas al orinar o defecar. Esta revisión no ha encontrado pruebas de la existencia de diferencias entre estos dos tipos de cirugía para estos resultados. La cirugía es más rápida con la histerectomía subtotal y hay menos pérdida de sangre y fiebre durante o después de la cirugía, pero es más probable que las mujeres presenten hemorragia menstrual continua, en comparación con la histerectomía total.



En la histerectomía mediante abordaje abdominal, se extrae el útero solo (histerectomía subtotal) o el útero y el cuello uterino (histerectomía total). Esta última es más frecuente, pero los resultados no se han comparado de forma sistemática.


Evaluar y comparar los resultados de la histerectomía subtotal versus la histerectomía abdominal total para las enfermedades ginecológicas benignas.

Estrategia de búsqueda:

Se efectuaron búsquedas en el registro especializado de ensayos controlados del Grupo Cochrane de Trastornos Menstruales y Subfertilidad (Cochrane Menstrual Disorders and Subfertility Group) (diciembre de 2005), Central (diciembre de 2005), Medline (1966 a diciembre de 2005), EmBase (1980 a diciembre de 2005), Biological Abstracts (1980 a diciembre de 2005), el National Research Register y las listas de citas pertinentes.

Criterios de selección:

Sólo se incluyeron ensayos controlados aleatorios de mujeres que se sometieron a una histerectomía total o subtotal debido a enfermedades ginecológicas benignas.

Recopilación y análisis de datos:

Se incluyeron tres ensayos con 733 participantes. Dos revisores seleccionaron los ensayos y extrajeron los datos de forma independiente, y compararon los resultados.

Resultados principales:

No hubo pruebas de la existencia de diferencias en las tasas de incontinencia, constipación o en las medidas de función sexual. En un ensayo no cegado, una proporción significativamente mayor de mujeres indicó que tenía episodios frecuentes de incontinencia urinaria después de la histerectomía subtotal comparada con la histerectomía total (OR 2,1; 1,02 a 4,3), pero estos resultados no se confirmaron en los otros dos ensayos que midieron la incontinencia de esfuerzo y de urgencia y la polaquiuria. . La duración de la cirugía y la cantidad de sangre perdida durante la cirugía se redujeron significativamente con la histerectomía subtotal comparada con la histerectomía total, pero no hubo pruebas de una diferencia en los odds de transfusión. Se observó una menor probabilidad de presentar morbilidad febril (OR 0,43; 0,25 a 0,75), y una mayor probabilidad de presentar hemorragia vaginal cíclica continua un año después de la cirugía (OR 11,3; 4,1 a 31,2), con la histerectomía subtotal que con la total. No hubo pruebas sobre diferencias en las tasas de otras complicaciones, la recuperación de la cirugía o las tasas de reingreso.

Conclusiones de los revisores:

Esta revisión no ha confirmado que la histerectomía subtotal ofrezca mejores resultados para la función sexual, urinaria o intestinal comparada con la histerectomía abdominal total. La cirugía es más corta y se reducen la pérdida de sangre intraoperatoria y la fiebre, pero las mujeres tienen mayor probabilidad de presentar hemorragia cíclica continua hasta un año después de la cirugía con la histerectomía subtotal que con la histerectomía total.

Esta revisión debería citarse como: Lethaby A, Ivanova V, Johnson NP. Histerectomía total versus subtotal para las enfermedades ginecológicas benignas (Revisión Cochrane traducida). En: La Biblioteca Cochrane Plus, número 4, 2007. Oxford, Update Software Ltd. Disponible en: (Traducida de The Cochrane Library, 2007 Issue 4. Chichester, UK: John Wiley & Sons, Ltd.).

Cribado de cancer cervical en adolescentes: a veces menos es mas

Clinical Practice Guideline Watch

Cervical Cancer Screening in Adolescents: Sometimes Less Is More

Updated guidelines state that HPV DNA testing has no role in the management of adolescents with abnormal Pap smears.

Elucidation of the link between cervical cancer and infection with high-risk types of human papillomavirus (HPV) has led to increased use of HPV DNA testing in the management of women with abnormal Pap smears. However, 80% of female adolescents become HPV DNA positive soon after their first sexual encounters, with the vast majority of these infections clearing spontaneously within 2 years. Hence, HPV DNA testing in adolescents with abnormal cervical cytology would lead to the referral of many adolescents for colposcopy even though they are at low risk for cervical cancer.

In 2006, the American Society for Colposcopy and Cervical Pathology (ASCCP) convened a consensus conference to update its evidence-based guidelines for managing women with abnormal cervical cancer screening tests. Based on current data on the ubiquity and natural history of HPV infection in teenagers and results from the National Cancer Institute–sponsored Atypical Squamous Cells of Undetermined Significance (ASC-US) Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study (ALTS), the consensus conference recommended that HPV DNA testing should not be used to manage adolescents with abnormal Pap smears.

New recommendations for adolescents (age, ≤20) are as follows:

  • Adolescents with ASC-US should undergo repeat Pap smears every 12 months. At 12 months, only adolescents with high-grade squamous intraepithelial lesion (HSIL) or greater should be referred for colposcopy. At 24 months, only those with ASC-US or greater should be referred for colposcopy.
  • Adolescents with LSIL should undergo repeat Pap smears every 12 months. At 12 months, only those with HSIL need to be referred for colposcopy. At 24 months, only those with ASC-US or greater should be referred.
  • In adolescents with either ASC-US or LSIL, “HPV DNA testing is unacceptable . . . and if inadvertently performed, should not influence management.”

Comment: Implementation of these recommendations will save money (the cost of an HPV DNA test can exceed US$100). In addition, teenagers will no longer need to worry about carrying a “high-risk” (cancer-causing) strain of HPV. Copies of the guidelines complete with algorithms can be downloaded from the American Society for Colposcopy and Cervical Pathology website.

When it comes to managing adolescents with abnormal Pap smears, doing less is better than doing more.

Alain Joffe, MD, MPH, FAAP

Published in Journal Watch Pediatrics and Adolescent Medicine December 12, 2007


Wright TC Jr et al. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol 2007 Oct; 197:346.

Medline abstract (Free)


2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests.

Wright TC Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D; 2006 American Society for Colposcopy and Cervical Pathology-sponsored Consensus Conference.

Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.

A group of 146 experts representing 29 organizations and professional societies met September 18-19, 2006, in Bethesda, MD, to develop revised evidence-based, consensus guidelines for managing women with abnormal cervical cancer screening tests. Recommendations for managing atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion (LSIL) are essentially unchanged. Changes were made for managing these conditions in adolescents for whom cytological follow-up for 2 years was approved. Recommendations for managing high-grade squamous intraepithelial lesion (HSIL) and atypical glandular cells (AGC) also underwent only minor modifications. More emphasis is placed on immediate screen-and-treat approaches for HSIL. Human papillomavirus (HPV) testing is incorporated into the management of AGC after their initial evaluation with colposcopy and endometrial sampling. The 2004 Interim Guidance for HPV testing as an adjunct to cervical cytology for screening in women 30 years of age and older was formally adopted with only very minor modifications.

PMID: 17904957 [PubMed – indexed for MEDLINE]

Journal Watch: Ginecologia


The Pill’s Cancer Protection Confirmed

Summary and Comment | Free

OC use for fewer than 8 years did not increase overall cancer rates, and it reduced gynecologic cancer risk in British women.

By Wendy S. Biggs, MD

October 18, 2007

Covering: Hannaford PC et al. BMJ 2007 Sep 29; 335:651

OC Effect on Bone Density: Still Not Clear

Summary and Comment | Subscription Required

Among female military cadets, oligomenorrhea and current OC use were associated with reduced BMD at certain skeletal sites.

By Diane E. Judge, APN/CNP

October 18, 2007

Covering: Ruffing JA et al. Nutr Metab (Lond) 2007 Aug 6; 4:17

Is HPV Testing Better Than the Pap Smear?

Summary and Comment | Free

As a screen for cervical neoplasia, HPV testing showed advantages over the Pap smear.

By Andrew M. Kaunitz, MD

October 17, 2007

Covering: Mayrand M-H et al. N Engl J Med 2007 Oct 18; 357:1579