Endometriosis: A Mystery Tour for the Clinician and
Patient
W. Ledger, W. Schlaff* and D. Olive**
Jessop Hospital for Women, Sheffield, United Kingdom
*Department of Obstetrics and Gynaecology
University of Colorado Health Sciences Centre, USA
**Department of Obstetrics and Gynaecology, Yale University School of Medicine, USA
Endometriosis is a chronic, recurring disease, often associated with infertility. It can affect
women at any stage in their lives, but is most common in the reproductive years. Despite high
incidence figures, the causes of endometriosis are still open to debate. In addition to
uncertainty over pathogenesis of the disease, endometriosis is often misdiagnosed leading to
delays in treatment, sometimes for several years. Such delay may result in disease
progression, lack of symptom control and increasing incidence of infertility. Symptoms of
endometriosis have been confused with conditions such as pelvic inflammatory disease,
irritable bowel syndrome or even psychosomatic problems.
By following a single case from first presentation, the chronic nature of endometriosis and the
problems faced by patients and clinicians will be illustrated.
Initial Presentation
Mrs B, a 32-year old woman, presented with pelvic pain and dysmenorrhea suggestive of
endometriosis. She was referred to a gynaecologist by her GP after several years of repeat
visits to him for the same problem. Her GP had previously tried prescribing the continuous
oral contraceptive pill (OCP) and a non-steroidal anti-inflammatory drug (mefenamic acid),
neither of which proved effective. Analgesics and the OCP are often prescribed in these
circumstances even though there is little robust data to support their use.
Diagnosis
At laparoscopy, widespread superficial endometriosis was visualized. Visible lesions were
treated with electro-diathermy. Many physicians and some patients feel that laparoscopy is
currently the only reliable way to confirm a diagnosis of endometriosis. The benefit of
laparoscopy is that it permits a ‘see and treat’ approach, though the effectiveness of
laparoscopy may be limited both by the nature of the disease and the surgeon’s skill.
Management
After initial improvement, her pain returned and she was given 6-months treatment with a
gonadotrophin-releasing hormone agonist (GnRHa), Zoladex. She became pain free and
amenorrhoeic, though she did experience hypoestrogenic side-effects such as hot flushes
and night sweats. After some discussion, it was decided to continue treatment with Zoladex
for a further 18 months with addback. The combination of GnRHa plus addback provided
continued relief from her endometriosis symptoms and protected her from menopausal-like
side-effects.
The observation that endometriosis is rarely seen in hypoestrogenic post-menopausal
women, led to the concept of treating the disease by inducing a pseudomenopausal state.
Continued exposure to GnRHas leads to a hypogonadal state with decreased release and
suppression of oestradiol from the ovaries. Use of GnRHas as a diagnostic test to determine
whether pelvic pain is oestrogen-related, is also currently being evaluated for patients who
continue to suffer pain when laparoscopy is unrevealing.
Repeat therapy or extended periods of treatment with GnRHas have previously been limited
due to their effects on bone mineral density (BMD). However, the loss of BMD does show a
gradual return towards baseline following treatment discontinuation. By giving addback using
an oestrogen/progestogen preparation with a GnRHa:
•
the impact of treatment on BMD loss is reduced
•
vasomotor symptoms such as hot flushes are relieved
•
efficacy of treatment on endometriosis symptoms is unaffected.1
Infertility
Mrs B and her husband returned expressing their desire to start a family, so GnRHatreatment was stopped. Although her periods resumed, she was unable to conceive and after
6 months she was experiencing severe dysmenorrhea. She was treated with a GnRHa for 3
months and then commenced in vitro fertilization (IVF) while still down-regulated. IVF was
successful and she later gave birth to a healthy son.
Endometriosis is often diagnosed in women with infertility (20–68%) and infertility is a
common sign of endometriosis.2 Controlled studies have shown that ablation of
endometriosis laparoscopically partially improves fertility, by approximately 13% over 1 year.2
As laparoscopy is an important part of any infertility work up, ablation of any lesions seen
during the procedure is suggested in order to improve fertility.
Disease Recurrence
Post-partum, Mrs B breast-fed for 6 months and was period free. When menstruation
resumed, she again suffered pain and other symptoms. Ultrasound revealed severe disease
with endometriomas present on both ovaries. Laparoscopically, bilateral ablation was
performed on the endometriomas followed by a further 3 months with a GnRHa. With Mrs B’s
desire for a second child, IVF was tried again. This was also successful, with the addition of a
daughter to the family.
Radical Surgery
Following the birth of her second child her endometriosis recurred and she requested
definitive treatment. She felt her family was complete and total abdominal hysterectomy with
bilateral oophorectomy was agreed as the next course of action. She is now well and
receiving hormone replacement therapy (HRT).
Ovarian cystectomy, oophorectomy, hysterectomy and total hysterectomy are radical options
which, while often curative, are unsuitable for women wishing to retain fertility. Following
radical surgery involving oophorectomy, patients often require HRT.
Conclusion
The enigma that is endometriosis requires decision making at every stage by physician and
patient alike. The complexities surrounding diagnosis, when to treat, sequence and
combinations of treatment all add up to a truly mysterious disease.
References
.1PICKERSGILL A. GnRH agonists and add-back therapy: is there a perfect combination? Br
J Obstet Gynaecol 105: 475–485, 1998.
.2MARCOUX S, MAHEUX R, BֹRUB ֹS et al. Laparoscopic surgery in infertile women with
minimal or mild endometriosis. NEJM 337(4): 217–222, 1997.