Dienogest for Endometriosis

Dienogest is a synthetic hormone used in the treatment of endometriosis. Hormonal treatments for endometriosis are limited, and in German-speaking countries, Dienogest and gonadotropin-releasing hormone (GnRH analogs) are the approved options [1]. Today, our focus will be on the progestogen Dienogest. I will explore how it works, potential side effects, and important considerations for those planning to conceive.

What is Dienogest?

Within your body, there are various sex hormones, and one of them is progesterone, also known as the corpus luteum hormone. It plays a vital role in your organism by preparing the uterine lining each month for a possible fertilized egg. This preparation facilitates the implantation and growth of a new life in the uterus. During this process, the uterine lining undergoes remodeling and received improved blood supply. Additionally, progesterone has an effect on the endometrium by reducing the number of estrogen receptors and acting as an anti-estrogenic agent [2].

Let me delve deeper into this concept. Receptors are essential for communication within the body, as they relay signals [3]. The reference to progesterone as an antagonist of estrogen is particularly significant. Estrogen, a sex hormone, is known to promote the growth of endometriosis lesions. Hence, using progesterone to counteract the influence of estrogen proves to be a smart approach. This is where Dienogest comes to pay. It is a synthetic form of progesterone, also known as a progestogen, commonly used in medicine.

From Surgery to Dienogest: The Evolution of Endometriosis Therapy

Let’s take a little historical excursion into the realm of endometriosis therapy. The journey to the current state of treatment was a progression over time. A pivotal milestone was the introduction of surgical interventions aimed at removing endometriosis lesions, which continue to be utilized today. Surprisingly, these surgical treatment options were developed as far back as the seventies and eighties. Before that, drug treatment primarily relied on a hormone called danazol [4, 5, 6]. However, this approach came with side effects, such as acne, weight gain, and the development of male body characteristics [7]. In the quest for alternative substances, researchers turned to progestins, among others, which showed great promise [8]. What makes progestins special is that they are derivatives of the body’s own corpus luteum hormone, resembling natural progesterone. This inherent similarity grants them a significant advantage – they can exert a comprehensive influence. Progestins not only act at the progesterone receptor but also interact with the estrogen receptor, androgen receptor, glucocorticoid receptor, and mineral corticoid receptor [9, 10].

Good to know!

Everything has a beginning, and the realm of synthetically produced luteal hormones (progestins) is no exception. Looking back at the past, we can identify three different generations in total.  The most recent generation includes progestins, which also encompass Dienogest. What sets it apart is its specific binding to the progesterone receptor while avoiding binding to other receptors. This unique characteristic helps prevent side effects and achieves a notable anti-estrogenic effect on the endometrium [9, 11].

How Dienogest Works

After its discovery, Dienogest quickly garnered attention for endometriosis treatment due to its potent effects on the endometrium, the lining of the uterus. You might already be familiar with synthetically produced progestins used in the contraceptive pill. Progestins are not only used for contraception but also for pain relief and overall symptom improvement in endometriosis. The German Society of Gynecology and Obstetrics recommends suitable progestins as a preferred option for symptomatic drug treatment of endometriosis [1].

Specifically, Dienogest exhibits the following effects:

  • Reduction of endometriosis lesions [12]
  • Inhibition of new nerve formation in affected regions [12]
  • Relief of chronic lower abdominal pain [13]
  • Reduction in the recurrence rate (reappearance of endometriosis lesions) [13]
  • Decrease in painful menstrual bleeding [12]

The undisputed efficacy of Dienogest in hormonal treatment warrants a closer look at why it can be helpful in endometriosis. To do so, we need to delve into the scientific literature. Studies conducted in test tubes and living organisms have revealed that Dienogest can inhibit uterine cell signaling [14]. This effect has been particularly observed in endometriosis cells located in the ovaries [15]. You may have come across the term “angiogenesis”, which refers to the formation of new blood vessels, distinct from existing ones. In studies, Dienogest has demonstrated the ability to slow down the formation of new blood vessels. This finding is critical as angiogenesis supplies endometriosis with nutrients, among other things [9].

This is why the term “drying up” is often used to describe the effects, although it is not entirely accurate. The foci themselves do not dry out, but the reduced supply of blood vessels and nutrients can make it more challenging for the endometriosis foci to grow and thrive.

Dienogest in Endometriosis: Experiences

Given that Dienogest is presently the sole progestogen officially approved for endometriosis, it is commonly prescribed in clinical practice. Let us delve into two studies that have investigated the effect of Dienogest in the context of endometriosis.

Dienogest Administered after Surgery

While hormonal treatments can provide relief from endometriosis, it is important to note that they do not cure the condition, nor do they guarantee the prevention of disease progression [16]. As a result, in some cases, surgery remains necessary, especially when sensitive structures like the ureter or intestine are affected [17, 18, 19]. A study was conducted to investigate the effect of Dienogest on women who had endometriosis lesions removed from their ovaries. The study group consisted of 203 patients, with an average age of 34.1 years. Following the surgical procedure, 90% of the patients took 2 mg of Dienogest daily for an average duration of 12 months. The observation period lasted about 30 months following surgery, during which the researcher monitored for adverse events and regrowth of endometriosis lesions [20].

Results: Results indicated that serious adverse side effects were not observed during the study, and endometriomas reappeared in only 3 patients [20].

Dienogest Optimizes Quality of Life and Relieves Pain

Another study investigated the impact of Dienogest on endometriosis, with a specific focus on symptom improvement. The study group consisted of 100 patients diagnosed with endometriosis who had not yet reached menopause. These patients were divided into 3 groups [21]:

  1. Women with freshly removed endometriosis lesions.
  2. Women with previously removed endometriosis lesions that later recurred.
  3. Women who had not undergone endometriosis surgery.

All study participants received 2 mg of Dienogest [21].

Results: Dienogest showed varying effects on the different groups of women. Hormonal treatment led to significant improvement in abdominal pain and quality of life for those who received the drug following surgery or who had not yet undergone surgery. However, patients who experienced a recurrence of endometriosis lesions after surgery did not benefit significantly from Dienogest [21].

How is Dienogest Taken?

Dienogest is a progestogen treatment that requires a prescription from your gynecologist. It is taken once a day, and the administration is similar to the use of the contraceptive pill. Typically, Dienogest is prescribed in a long cycle [12]. It is essential to closely cooperate with your gynecologist during the treatment of endometriosis. They will monitor the endometriosis lesions and determine the most suitable treatment plan for your specific case. This includes evaluating any potential side effects and determining if surgery may be advisable. Please note: It is important to note that Dienogest is not intended for contraception, but is specifically approved for the treatment of endometriosis [1]. Based on studies and empirical evidence from practice, a dosage of 2 mg of Dienogest is often recommended, as it has shown promising results with manageable side effects [22, 23].

Dienogest and the Desire to Have Children

When taking Dienogest, ovulation is typically suppressed, which prevents pregnancy from occurring. However, it is essential to know that your general fertility is not adversely affected by the drug. If you have a desire to have a child, it is crucial to discuss this with your gynecologist. They can tailor the therapy accordingly to accommodate your plans for pregnancy.

Dienogest: Possible Side Effects

Dienogest intervenes in the hormonal composition of your body, which is beneficial in the case of endometriosis, as it counteracts the effects of the sex hormone estrogen, known to accelerate endometriosis growth. However, being a drug, Dienogest may come with some side effects, though they are not experienced by everyone.

Potential side effects include:

  • Irregular bleeding [21]
  • Reduced menstrual flow [21]
  • Absence of menstruation [21]
  • Weight gain [21]
  • Hair loss [21]
  • Back pain [21]
  • Headaches [20]
  • Skin issues [20]
  • Depressive moods [20]
  • Gastrointestinal problems [20]
  • Fluid retention [20]
  • Hot flashes [20]

While Dienogest may be a suitable treatment option for patients with endometriosis, it is important to remember that not everyone experiences all of these side effects. Many women have little or no side effects. Additionally, when considering reports from social media, it is essential to be aware that those who comment are often individuals who may have experienced certain side effects.

To find the most appropriate treatment for you, it is best to discuss your specific situation with your gynecologist. If Dienogest is recommended, try it out with an open mind, and if any side effects occur, discuss them promptly with your gynecologist for proper management.

Good to know!

The drug Dienogest has been associated with a potential negative effect on bone density. As a result, adolescent women (teenagers) should approach the use of Dienogest with careful consideration in consultation with their doctor. Since bones are still growing during adolescence, it is crucial to assess the individual risk of osteoporosis (the risk of bone loss) before considering Dienogest as a treatment option [24].

In a Nutshell

Endometriosis can be influenced by estrogen, but progesterone can counteract its effects. Artificial luteal hormones such as Dienogest are considered pioneers in the hormonal treatment of endometriosis. Studies and real-world experience have shown that Dienogest can effectively reduce endometriosis lesions, alleviate pain, and lower the risk of new lesions by interfering with signaling pathways and inhibiting new blood vessel formation. Commonly, 2 mg of Dienogest is taken in a long-term cycle. Side effects may include irregular bleeding, headaches, and skin issues. Since Dienogest selectively affects the hormone balance, it requires a prescription and should be discussed with your gynecologist.

The Endo-App provides further information on treatment options and helpful tips for living with endometriosis. Download the Endo-App to access expert knowledge and support.

References

  1. German Society of Gynecology and Obstetrics: Guideline Program. Diagnosis and therapy of endometriosis. August 2020.
  2. Diedrich, Klaus.Gynecology and Obstetrics (Springer Textbook) (German Edition) (S.65). Springer Berlin Heidelberg. Kindle-Version.
  3. Gesundheitsinformation.de: Rezeptoren
  4. Rönnberg L, Ylöstalo P, Järvinen PA. Effects of danazol in the treatment of severe endometriosis. Postgrad Med J. 1979;55 Suppl 5:21-6. PMID: 537949.
  5. Rannevik G. Hormonal, metabolic and clinical effects of danazol in the treatment of endometriosis. Postgrad Med J. 1979;55 Suppl 5:14-20. PMID: 537948.
  6. Biberoglu KO, Behrman SJ. Dosage aspects of danazol therapy in endometriosis: short-term and long-term effectiveness. Am J Obstet Gynecol. 1981 Mar 15;139(6):645-54. doi: 10.1016/0002-9378(81)90478-6. PMID: 6452062.
  7. Farquhar  C, Prentice  A, Singla  AA, Selak  V. Danazol for pelvic pain associated with endometriosis. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD000068. DOI: 10.1002/14651858.
  8. Luciano AA, Turksoy RN, Carleo J. Evaluation of oral medroxyprogesterone acetate in the treatment of endometriosis. Obstet Gynecol. 1988 Sep;72(3 Pt 1):323-7. PMID: 2970029.
  9. Lazzeri L, Luisi S, Petraglia F. Progestins for the Treatment of Endometriosis: An Update. Journal of Endometriosis. 2010;2(4):169-181. doi:10.1177/228402651000200401
  10. Sitruk-Ware R. New progestagens for contraceptive use. Hum Reprod Update. 2006 Mar-Apr;12(2):169-78. doi: 10.1093/humupd/dmi046. Epub 2005 Nov 16. PMID: 16291771.
  11. Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH. Classification and pharmacology of progestins. Maturitas. 2008 Sep-Oct;61(1-2):171-80. doi: 10.1016/j.maturitas.2008.11.013. PMID: 19434889.
  12. Ferrero S, Remorgida V, Venturini PL, Bizzarri N. Endometriosis: the effects of dienogest. BMJ Clin Evid. 2015 Jun 9;2015:0802. PMID: 26057101; PMCID: PMC4461025.
  13. Takaesu Y, Nishi H, Kojima J, Sasaki T, Nagamitsu Y, Kato R, Isaka K. Dienogest compared with gonadotropin-releasing hormone agonist after conservative surgery for endometriosis. J Obstet Gynaecol Res. 2016 Sep;42(9):1152-8. doi: 10.1111/jog.13023. Epub 2016 May 26. PMID: 27225336.
  14. Shimizu Y, Mita S, Takeuchi T, Notsu T, Mizuguchi K, Kyo S. Dienogest, a synthetic progestin, inhibits prostaglandin E2 production and aromatase expression by human endometrial epithelial cells in a spheroid culture system. Steroids. 2011 Jan;76(1-2):60-7. doi: 10.1016/j.steroids.2010.08.010. Epub 2010 Sep 21. PMID: 20851710.
  15. Horie S, Harada T, Mitsunari M, Taniguchi F, Iwabe T, Terakawa N. Progesterone and progestational compounds attenuate tumor necrosis factor alpha-induced interleukin-8 production via nuclear factor kappa B inactivation in endometriotic stromal cells. Fertil Steril. 2005 May;83(5):1530-5. doi: 10.1016/j.fertnstert.2004.11.042. PMID: 15866594.
  16. Falcone, Tommaso MD; Flyckt, Rebecca MD Clinical Management of Endometriosis, Obstetrics & Gynecology: March 2018 – Volume 131 – Issue 3 – p 557-571
    doi: 10.1097/AOG.0000000000002469
  17. Grandi G, Barra F, Ferrero S, Sileo FG, Bertucci E, Napolitano A, Facchinetti F. Hormonal contraception in women with endometriosis: a systematic review. Eur J Contracept Reprod Health Care. 2019 Feb;24(1):61-70. doi: 10.1080/13625187.2018.1550576. Epub 2019 Jan 21. PMID: 30664383.
  18. Barra F, Scala C, Biscaldi E, Vellone VG, Ceccaroni M, Terrone C, Ferrero S. Ureteral endometriosis: a systematic review of epidemiology, pathogenesis, diagnosis, treatment, risk of malignant transformation and fertility. Hum Reprod Update. 2018 Nov 1;24(6):710-730. doi: 10.1093/humupd/dmy027. PMID: 30165449.
  19. Millochau JC, Abo C, Darwish B, Huet E, Dietrich G, Roman H. Continuous Amenorrhea May Be Insufficient to Stop the Progression of Colorectal Endometriosis. J Minim Invasive Gynecol. 2016 Jul-Aug;23(5):839-42. doi: 10.1016/j.jmig.2016.04.008. Epub 2016 Apr 26. PMID: 27130533.
  20. Chandra A, Rho AM, Jeong K, Yu T, Jeon JH, Park SY, Lee SR, Moon HS, Chung HW. Clinical experience of long-term use of dienogest after surgery for ovarian endometrioma. Obstet Gynecol Sci. 2018 Jan;61(1):111-117. doi: 10.5468/ogs.2018.61.1.111. Epub 2017 Dec 18. PMID: 29372157; PMCID: PMC5780305.
  21. Jeong SH, Lee D, Kim SK, Jee BC. Symptom-alleviating effect and adverse effect of dienogest in Korean women with endometriosis. Gynecol Endocrinol. 2018 Nov;34(11):970-974. doi: 10.1080/09513590.2018.1469610. Epub 2018 May 7. PMID: 29733226.
  22. Köhler G, Faustmann TA, Gerlinger C, Seitz C, Mueck AO. A dose-ranging study to determine the efficacy and safety of 1, 2, and 4mg of dienogest daily for endometriosis. Int J Gynaecol Obstet. 2010 Jan;108(1):21-5. doi: 10.1016/j.ijgo.2009.08.020. Erratum in: Int J Gynaecol Obstet. 2011 Mar;112(3):257. PMID: 19819448.
  23. Harada T, Taniguchi F. Dienogest: a new therapeutic agent for the treatment of endometriosis. Womens Health (Lond). 2010 Jan;6(1):27-35. doi: 10.2217/whe.09.72. PMID: 20001868.
  24. Ebert AD, Dong L, Merz M, Kirsch B, Francuski M, Böttcher B, Roman H, Suvitie P, Hlavackova O, Gude K, Seitz C. Dienogest 2 mg Daily in the Treatment of Adolescents with Clinically Suspected Endometriosis: The VISanne Study to Assess Safety in ADOlescents. J Pediatr Adolesc Gynecol. 2017 Oct;30(5):560-567. doi: 10.1016/j.jpag.2017.01.014. Epub 2017 Feb 9. PMID: 28189702.
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Dipl.-Ges.oec. Jennifer Ann Steinort
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