Sexual function in endometriosis patients

Around 10% of fertile women suffer from endometriosis with or without
adenomyosis (AD), affecting up to 190 million women worldwide.[1] This
corresponds to approximately 400,000 women in the Netherlands.
The management of patients with (deep infiltrating) endometriosis and/or
adenomyosis includes conservative management, as well as surgical and medical
treatments.
Conservative management may consist of psychological support, adequate pain
management, pelvic floor physiotherapy and/or dietary interventions, such as
the low-FODMAP diet.
Medical options include hormonal treatments such as oral contraceptives,
progestogens, GnRH agonists and aromatase inhibitors. Treatment choice depends
on the severity of symptoms, patient*s preferences, current wish to have
children, potential side effects and/or contra-indications.

Surgical treatment includes laparoscopic resection of endometriosis lesions. In
severe DIE, extensive surgery may involve the removal of endometriotic nodules,
including procedures such as Low Anterior Resections (LAR) and excision of deep
infiltrating endometriosis at the uretero-vesical junction, to diminish
dysmenorrhea and complications associated with endometriosis.

Influence of endometriosis on quality of life is well examined and
endometriosis has not only physical but also psychological effects, causing
depression, anxiety, and compromising social relationships. Furthermore,
endometriosis negatively impacts sexual life and social life. Additionally, it
leads to a loss of productivity at work and significant utilization of health
resources. [2]

Evidence from multiple studies suggests that surgical treatment positively
impacts sexual functioning. Recent prospective studies assessing sexual
function at multiple time points before and after surgical treatment, show that
surgical intervention results in improved FSFI scores. [3, 4]. However, there
is still a need for further targeted research on sexual function following
endometriosis surgery, with sufficiently large sample sizes. Given that we will
conduct this research in an expert clinic, we expect to be able to recruit a
substantial sample size.

Less is known about the effect of medical treatment on sexual function. A few
studies have investigated this effect, showing improvements in sexual function
[5, 6, 7]. Conversely, another study demonstrated a deterioration in sexual
functioning following hormonal treatment [8]. Additionally, most studies
conducted on this subject have often assessed only a single medication.
The limited evidence and conflicting results, along with focus on only a single
medication in most conducted studies, demonstrate the need for additional
research into the effects of pharmacological treatment options on sexual
functioning.

Conservative treatments, such as dietary interventions, pelvic floor
physiotherapy and psychological support, are suggested to positively influence
the sexual functioning of patients with endometriosis.[9, 10, 11] However, the
evidence regarding the effect of these treatments on sexual functioning remains
limited.

Classification of DIE is done by using the Enzian-classification. [12] This
classification provides a uniform description and detailed overview of the
extent and location of DIE.
The research conducted on the Enzian-classification is currently limited.
Research suggests a correlation between the severity grade in
Enzian-classification and pain scores. [13] Other research showed an
association between dyspareunia and endometriosis lesions in compartment B of
the Enzian-classification, corresponding with the uterosacral ligaments. [14]
A study of Bafort et al. investigated pain scores pre- and post-surgery,
showing a weak but significance improvements in dyspareunia in patients with
the surgical phenotype *rectovaginal endometriosis*.[15] However, this study
did not use standardized sexual function questionnaires, and the
Enzian-classification was assessed post hoc.
These findings suggest a potential correlation between Enzian-classification
and sexual functioning, highlighting the need for further research on the
impact of treatment on sexual function, based on Enzian-classification.
Understanding the relationship between the Enzian-classification and sexual
functioning could contribute to valuable insights for personalized, targeted
treatment choices for patients, helping patients gain a clearer perspective on
their potential treatment outcomes.

References:
1. Zondervan, K. T., Becker, C. M., & Missmer, S. A. (2020). Endometriosis. The
New England Journal of Medicine., 382(13), 1244-1256.
https://doi.org/10.1056/NEJMra1810764
2. Young, K.; Fisher, J.; Kirkman, M. Women*s experiences of endometriosis: A
systematic review and synthesis of qualitative research. J. Fam. Plann. Reprod.
Health Care 2015, 41, 225-234.
3. Dior UP, Reddington C, Cheng C, Levin G, Healey M. Sexual Function of Women
With Deep Endometriosis Before and After Surgery: A Prospective Study. J Sex
Med. 2022 Feb;19(2):280-289. doi: 10.1016/j.jsxm.2021.11.009. Epub 2021 Dec 18.
PMID: 34930708.
4. Mehdizadehkashi A, Chaichian S, Rokhgireh S, Tahermanesh K, Mirgaloybayat S,
Saadat Mostafavi R, Khodaverdi S, Ajdary M, Ahmadi Pishkuhi M. Does
laparoscopic treatment of deep endometriosis improve sexual dysfunction.
Caspian J Intern Med. 2023 Spring;14(2):349-355. doi: 10.22088/cjim.14.2.267.
PMID: 37223304; PMCID: PMC10201115.
5. Vercellini P, Frattaruolo MP, Somigliana E, Jones GL, Consonni D, Alberico
D, Fedele L. Surgical versus low-dose progestin treatment for
endometriosis-associated severe deep dyspareunia II: effect on sexual
functioning, psychological status and health-related quality of life. Hum
Reprod. 2013 May;28(5):1221-30. doi: 10.1093/humrep/det041. Epub 2013 Feb 26.
PMID: 23442755.
6. Vercellini P, Bracco B, Mosconi P, Roberto A, Alberico D, Dhouha D,
Somigliana E. Norethindrone acetate or dienogest for the treatment of
symptomatic endometriosis: a before and after study. Fertil Steril. 2016
Mar;105(3):734-743.e3. doi: 10.1016/j.fertnstert.2015.11.016. Epub 2015 Dec 8.
PMID: 26677792.
7. Caruso S, Iraci M, Cianci S, Vitale SG, Fava V, Cianci A. Effects of
long-term treatment with Dienogest on the quality of life and sexual function
of women affected by endometriosis-associated pelvic pain. J Pain Res. 2019 Jul
29;12:2371-2378. doi: 10.2147/JPR.S207599. PMID: 31536046; PMCID: PMC6681157.
8. Biasioli A, Zermano S, Previtera F, Arcieri M, Della Martina M, Raimondo D,
Raffone A, Restaino S, Vizzielli G, Driul L. Does Sexual Function and Quality
of Life Improve after Medical Therapy in Women with Endometriosis? A
Single-Institution Retrospective Analysis. J Pers Med. 2023 Nov 25;13(12):1646.
doi: 10.3390/jpm13121646. PMID: 38138873; PMCID: PMC10745063.
9. van Haaps AP, Wijbers JV, Schreurs AMF, Vlek S, Tuynman J, De Bie B, de
Vogel AL, van Wely M, Mijatovic V. The effect of dietary interventions on pain
and quality of life in women diagnosed with endometriosis: a prospective study
with control group. Hum Reprod. 2023 Dec 4;38(12):2433-2446. doi:
10.1093/humrep/dead214. PMID: 37877417; PMCID: PMC10754387.
10. Jorge CH, Bø K, Chiazuto Catai C, Oliveira Brito LG, Driusso P, Kolberg
Tennfjord M. Pelvic floor muscle training as treatment for female sexual
dysfunction: a systematic review and meta-analysis. Am J Obstet Gynecol. 2024
Jul;231(1):51-66.e1. doi: 10.1016/j.ajog.2024.01.001. Epub 2024 Jan 6. PMID:
38191016.
11. Barbara G, Facchin F, Meschia M, Berlanda N, Frattaruolo MP, VercellinI P.
When love hurts. A systematic review on the effects of surgical and
pharmacological treatments for endometriosis on female sexual functioning. Acta
Obstet Gynecol Scand. 2017 Jun;96(6):668-687. doi: 10.1111/aogs.13031. Epub
2016 Nov 5. PMID: 27687240.
12. Keckstein, J., Saridogan, E., Ulrich, U. A., Sillem, M., Oppelt, P.,
Schweppe, K. W., Krentel, H., Janschek, E.

Primary Objective: To study the effect of different treatment approaches -
existing of conservative management, pharmacological treatment and surgical
treatment - on sexual function in patients diagnosed with endometriosis.

Secondary Objective(s): Enzian Classification and relation to sexual function.

This will be a prospective cohort study. Patients visiting the endometriosis
unit of the HMC
hospital with complaints of endometriosis will be examined during their first
visit on the outpatient clinic. There will be determined whether there is
endometriosis. Subsequently, treatment will be initiated, consisting of a
conservative management approach, pharmacological treatment, or surgical
intervention. Patients will receive questionnaires at several moments before
and during their treatment.

In case of deep infiltrating endometriosis, the severity of DIE will be
classified through the Enzian-classification as usual.[12] The #Enzian
classification is based on the known Enzian classification for (DI)E using
three compartments (A*vagina, rectovaginal space (RVS); B*uterosacral ligaments
(USL) / cardinal ligaments/pelvic sidewall and C*rectum) as well as so-called F
(ie far locations) such as the urinary bladder (FB), the ureters (FU), and
other extragenital lesions (FO). It additionally covers the involvement of the
peritoneum (P), ovary (O), other intestinal locations (sigmoid colon, small
bowel; FI), as well as adhesions, involving the tubo-ovarian unit (T) and,
optionally, tubal patency.
- Individual compartments or organ involvement are identified with capital
letters (P, O, T, A, B, C, F) and arranged in this order.
- The extent of endometriosis is represented by the numbers 1, 2 and 3 in
compartments P, O, T, A, B, and C.
- Paired organs (ovary, tube, USL, parametrium, ureter): the severity is
arranged separately after the letter (left / right).
- Missing / invisible ovary or tube are described with suffix (m, missing; x,
unknown).

At various points during the treatment, questionnaires will be administered
regarding the patients' sexual function.

Sexual function will be measured by Female Sexual Function Index (FSFI) and
Female Sexual Distress Scale (FSDS). The FSFI is a questionnaire aimed to
assess sexual function in women, consisting of 19 questions that include pain,
orgasm, sexual desire, arousal, lubrication, pain and satisfaction. [16] The
FSDS consists of 12 questions and is developed to measure sexually related
personal distress in women. [17] Both questionnaires have been validated and
proven reliable, and their psychometric properties are well replicated in a
Dutch sample.[18]
General Quality of Life will be measured by Endometriosis Health Profile-30
(EHP-30). This questionnaire measures the health-related quality of life in
endometriosis patients.[19] The Dutch EHP-30 has proven to be a useful tool in
researching the effect of endometriosis on health status.[20]
Duration of this study is three years. During the follow-up period, data
collection will last for a maximum of 12 months after inclusion. Information
regarding treatment will be collected after inclusion. For conservative
management, the applied conservative interventions will be recorded, including,
for example, dietary interventions, adequate pain management, psychologist
consultations, or pelvic floor physiotherapy. For pharmacological management,
the specific medication used, including dosage and frequency, will be
documented. In case of surgery, the type of surgery will be noted, such as
resection of superficial endometriosis, bowel surgery, resection of DIE,
treatment of endometrioma, etc. Additionally, when pharmacological or surgical
management is applied, any concurrent conservative interventions will also be
recorded.
FSFI, FSDS and EHP-30 will be conducted at T0, T1, T2, and T3. T0 represents
the first set of questionnaires, which will be sent after signing the informed
consent. The second, third, and fourth set of questionnaires will follow,
respectively, three (T1), six (T2), and twelve (T3) months after:
- the initial outpatient visit, in the case of conservative management;
- the initiation of pharmacological therapy;
- surgical treatment.
Baseline characteristics will be collected such as age, BMI, education,
relationship status, labour participation, medical history, duration of
complaints, character of complaints, parity, desire to have children.
Treatment is categorised in conservative management, pharmacological treatment
and surgical treatment. The three study groups will be analyzed independently
and will not be subject to comparative analysis due to the considerable risk of
bias.

The Enzian classification will be determined through transvaginal ultrasound
during the initial visit. This classification will be analyzed in relation to
sexual function (FSFI and FSDS) and quality of life (EHP-30) at T0, without
considering treatment effect.

Data will be collected in the data management system Castor EDC. Data will be
collected by the investigators, nurses of the endometriosis department and a
research student.

References:
16. Rosen R, Brown C, Heiman J, Leiblum S, Meston C, Shabsigh R, Ferguson D,
D'Agostino R Jr. The Female Sexual Function Index (FSFI): a multidimensional
self-report instrument for the assessment of female sexual function. J Sex
Marital Ther. 2000 Apr-Jun;26(2):191-208. doi: 10.1080/009262300278597. PMID:
10782451.
17. Derogatis LR, Rosen R, Leiblum S, Burnett A, Heiman J. The Female Sexual
Distress Scale (FSDS): initial validation of a standardized scale for
assessment of sexually related personal distress in women. J Sex Marital Ther.
2002 Jul-Sep;28(4):317-30. doi: 10.1080/00926230290001448. PMID: 12082670.
18. ter Kuile MM, Brauer M, Laan E. The Female Sexual Function Index (FSFI) and
the Female Sexual Distress Scale (FSDS): psychometric properties within a Dutch
population. J Sex Marital Ther. 2006 Jul-Sep;32(4):289-304. doi:
10.1080/00926230600666261. PMID: 16709550.
19. Jones G, Kennedy S, Barnard A, Wong J, Jenkinson C. Development of an
endometriosis quality-of-life instrument: The Endometriosis Health Profile-30.
Obstet Gynecol. 2001 Aug;98(2):258-64. doi: 10.1016/s0029-7844(01)01433-8.
PMID: 11506842.
20. van de Burgt TJ, Kluivers KB, Hendriks JC. Responsiveness of the Dutch
Endometriosis Health Profile-30 (EHP-30) questionnaire. Eur J Obstet Gynecol
Reprod Biol. 2013 May;168(1):92-4. doi: 10.1016/j.ejogrb.2012.12.037. Epub 2013
Jan 31. PMID: 23375903.

The burden of the study involves filling out the questionnaires, which will
take approximately 15 minutes per measuring moment. In total, this amounts to 1
hour of their time. There are no further risks associated with filling out the
questionnaires. Another potential burden may arise from the possible discomfort
experienced when answering questions related to sexuality.