Overview

Endometriosis and uterine fibroids (also known as uterine leiomyomas) are common gynaecological conditions affecting large numbers of women worldwide. While they have distinct causes and symptoms, their overlap in characteristics such as genetic profile can complicate diagnosis.

Many women are asymptomatic but those with symptoms require medical intervention to relieve chronic pain and dysmenorrhea. Management often involves drug delivery systems targeting symptoms and underlying mechanisms. Both conditions also pose challenges for fertility, emphasising the need for specific treatments and consideration during pregnancy planning.

Endometriosis

Endometriosis is a disease of adolescents and reproductive-aged women in which the tissue similar to the inner lining of the uterus grows outside the uterine cavity. The consequence of endometriosis is chronic pelvic pain, severe dysmenorrhea, dyspareunia(pain during sex), and infertility.

The disease is characterised by oestrogen-dependent growth of the endometrial glands and stroma outside the endometrial cavity.¹

Causes 

• Retrograde menstruation: During menstruation, menstrual blood containing endometrial cells flows backward through the fallopian tubes into the pelvic cavity instead of exiting the body. These displaced endometrial cells can attach to pelvic organs and grow, leading to endometriosis
• Embryonic cell transformation: Another theory proposes that embryonic cells lining the pelvic organs may transform into endometrial-like cell implants during puberty, due to hormonal changes. These implants can develop into endometriosis lesions over time
• Surgical scars: Surgical procedures such as hysterectomy or C-sections may inadvertently spread endometrial cells to other pelvic areas, leading to the development of endometriosis in some cases
• Immune system disorders: Issues with the immune system may make some women more susceptible to endometriosis. Immune system abnormalities could prevent the body from recognizing and destroying misplaced endometrial tissue
• Hormonal factors: Hormonal imbalances, particularly elevated levels of oestrogen relative to progesterone, may contribute to the development and progression of endometriosis. Oestrogen promotes the growth of endometrial tissue, while progesterone inhibits it
• Genetic predisposition: Endometriosis tends to run in families, suggesting a genetic component. Certain genetic variations may increase the likelihood of developing the condition

Signs and symptoms 

• Chronic pelvic pain:before and during menstruation. The pain may also intensify over time
• Painful periods (Dysmenorrhea): severe menstrual cramps that may start before menstruation and last throughout the period
• Painful intercourse (Dyspareunia): pain during or after sexual intercourse, particularly deep penetration
• Pain with bowel movements or urination: especially during menstruation
• Excessive bleeding or bleeding between periods
• Infertility: difficulty getting pregnant or experiencing recurrent miscarriages
• Fatigue: persistent low energy levels, often due to chronic pain and disrupted sleep patterns
• Digestive issues: considerable effects on their bowel habits, including alternating constipation and diarrhoea, painful emptying of their bowels (dyschezia), or blood in the stool(in particular perimenstrual)
• Lower back pain that worsens during menstruation

Diagnosis of endometriosis

Diagnosis of this condition usually starts with a clinical assessment and a review of the patient’s medical history, looking out for any of the aforementioned symptoms. It may follow with physical examination that can range from a simple observation to pelvic ultrasounds, transvaginal ultrasound scans or MRI. However, the most reliable diagnostic method relies on the examination of tissues extracted from the area of concern, and an internal observation of such areas via laparoscopic surgery.⁷

Risk factors

Menstrual and reproductive history

Earlier age at menarche (<12 years) and shorter menstrual cycles (<26 days) are associated with a higher incidence of endometriosis, likely due to increased frequency of retrograde menstruation or hormonal changes.²

Anthropometry

A consistent trend suggests that lower body mass index (BMI) in adulthood is linked to a higher likelihood of endometriosis among individuals. This association seems to extend from adulthood to childhood, with childhood leanness also associated with an increased risk of endometriosis.³

Diet

Dietary factors also play a role, with varying findings across studies. A study observed a reduced risk of endometriosis with higher consumption of green vegetables and fruit, while red meat intake showed an increased risk.⁴ Additionally, omega-3 fatty acids have shown a protective effect, while trans-unsaturated fats may increase the risk.

Smoking

Smoking has been observed to decrease oestrogen levels. However, it also introduces individuals to estrogenic endocrine disruptors such as dioxin, which can add complexity to this association.⁵

Adenomyosis

Adenomyosis, characterised by the invasion of endometrial tissue into the myometrium, shares symptoms with endometriosis but is recognised as a distinct condition. Research has shown a higher prevalence of adenomyosis among women surgically confirmed to have endometriosis compared to those without.⁶

Treatment

Treatment for Endometriosis-Associated Pain

Surgical options:

• Laparoscopic surgery to remove or coagulate peritoneal implants and ovarian endometriomas⁸
• Conservative ovarian surgery, such as draining cysts without removing the ovary⁹
• Excision of ovarian endometriomas has shown better pain relief and lower recurrence rates compared to cyst vaporisation or coagulation⁹
• Resection of rectovaginal lesions, although associated with higher complication rates, can provide good pain relief, especially in the short-term¹⁰ 

Medical therapy:

• Hormonal compounds like GnRH agonists are used to inhibit ovulation and suppress endometrial cell proliferation. While effective against pain, GnRH agonists have significant hypoestrogenic adverse effects and are often used with add-back therapy to reduce side effects^11,13
• Oral contraceptives and progestins have the same goal as GnRH agonists and are for long-term management due to their safety, efficacy, and tolerability^11,12

Treatment for Endometriosis-Associated Infertility

Surgical options:

• Adhesiolysis and removal of endometriotic lesions may improve fertility, especially in cases of early-stage disease¹³
• Surgery for ovarian endometriotic cysts may enhance spontaneous pregnancy rates
• Laparoscopic excision of endometriomas should be balanced with the risk of ovarian reserve damage¹⁴

Assisted Reproductive Techniques (ART):

• In vitro fertilisation (IVF) bypasses the negative effects of endometriosis on fertility by directly retrieving oocytes from the ovaries and transferring embryos to the uterus¹⁵
• IVF is preferred for women with more advanced endometriosis or those who have failed to conceive with other treatments¹⁵
• Gonadotropin-releasing hormone (GnRH) agonists may be used before IVF to improve outcomes by reducing inflammation¹⁵
• Intrauterine insemination (IUI) may be considered for women with minimal or mild endometriosis, especially when combined with controlled ovarian hyperstimulation¹⁶

Potential complications

• Possible uterine rupture during pregnancy or delivery: In rare cases, endometriosis located at the uterine isthmus may weaken the posterior uterine wall, predisposing it to uterine rupture during pregnancy or delivery¹⁷
• Adverse pregnancy outcomes: Endometriosis can lead to adverse pregnancy outcomes, including placenta previa and preterm birth. These complications occur even in the absence of assisted reproductive technology (ART) treatment. Placenta previa risk is associated with deep endometriosis, while preterm birth risk is related to ovarian endometriosis¹⁸
• Endometriosis surgery by laparoscopy or laparotomy can be associated with various types of intestinal complications that may occur in the immediate postoperative period or later. They include bowel anastomotic dehiscence, rectovaginal fistula, anastomotic bleeding, intra-abdominal infections, wound infections, bowel stricture, intestinal obstruction, chronic constipation, and diarrhoea
• Possible intraperitoneal bleeding, infected or ruptured endometrioma, or uterine rupture during pregnancy: Women with endometriosis may experience nonspecific abdominal pain during pregnancy, which could indicate intraperitoneal bleeding, infected or ruptured endometrioma, or uterine rupture. Proper management is necessary to ensure the best outcome for both mother and fetus¹⁷

Fibroids

Uterine fibroids, also known as leiomyomas or myomas, are benign tissue clusters within the uterus of smooth muscle cells and fibroblasts.¹⁹ They are the most prevalent noncancerous tumours found in women of childbearing age. These lesions disrupt the functions of the uterus.

Causes and risk factors

Early menarche

Studies suggest that an early age of menarche increases the risk of fibroids. This risk factor is also observed in other hormonally mediated conditions such as endometrial and breast cancers.^20,21

Parity and pregnancy

Parity, or the number of pregnancies a woman has had, has been inversely associated with the risk of fibroid development. Studies have shown a protective effect of pregnancy against fibroids. It is suggested that postpartum uterine remodelling and selective apoptosis of small lesions may contribute to this protective effect.²²

Caffeine intake

Recent evidence suggests a relationship between alcohol and caffeine intake and the risk of developing fibroids, especially among younger women. Current drinkers and those with high caffeine intake were found to have significantly higher risks of fibroids. The association appears to have a dose-response relationship.^23,24

Other possible factors

Various factors such as:

• Uterine infection
• Hormonal fluctuations
• Metabolic disorders
• Dietary habits
• Stress

Environmental influences 

Clinical features

Uterine fibroids are classified based on location: 

• Subserosal (projecting outside the uterus)
• Intramural (within the myometrium)
• Submucosal (projecting into the uterine cavity)

The symptoms and treatment options are affected by the size, number, and location of the tumours.

Common symptoms:

• Abnormal uterine bleeding, often characterised by excessive menstrual bleeding, is the most prevalent symptom.-Excessive bleeding can lead to the development of anaemia
• Urinary symptoms include increased urinary frequency, incontinence and hesitancy
• Gastrointestinal symptoms such as constipation and tenesmus (the recurrent need to void bowels)

Other symptoms may include:

• Pelvic pressure
• Bowel dysfunction
• Low back pain
• Constipation
• Dyspareunia (painful intercourse)

Diagnosis

• Clinical Diagnosis: The evaluation of fibroids is primarily based on the patient's presenting symptoms, including abnormal menstrual bleeding, bulk symptoms, pelvic pain, or findings suggestive of anaemia
• Precise uterine fibroid mapping, involving localization, measurement, and characterization, for understanding the natural progression of these tumours and assessing responses to treatment²⁵

Accurate assessment of myomas' size, number, and position for optimal patient selection for medical therapy, noninvasive procedures, or surgery.²⁵

Imaging techniques used to confirm the diagnosis of myomas include:

• Ultrasonography is the preferred initial imaging modality for fibroids. Transvaginal ultrasonography is highly sensitive (about 90% to 99%) for detecting uterine fibroids but may miss subserosal or small fibroids. Adding sonohysterography or hysteroscopy can improve sensitivity for detecting submucosal myomas²⁶
• Saline infusion sonohysterography is often utilised as an additional imaging tool to complement B-mode ultrasound for characterising focal uterine masses
• MRI -Magnetic resonance imaging (MRI), although more expensive, is considered the most sensitive modality for assessing uterine myomas, especially for detecting small fibroids.²⁸ MRI is also effective in distinguishing between leiomyoma and focal adenomyosis. Compared to ultrasound, MRI offers greater sensitivity in detecting uterine fibroids, avoids the use of ionising radiation, and provides clear visualisation of uterine zonal anatomy^29,30

Complications of fibroids during pregnancy:

• Increased risk of preterm delivery
• Higher incidence of premature rupture of membranes
• Elevated risk of placental abruption
• Greater likelihood of foetal malformation
• A higher rate of caesarean section
• Increased incidence of postpartum haemorrhage
• Elevated risk of foetal malpresentation
• Fibroids may also be associated with miscarriage²⁷

Treatments

Medical Treatments

Currently, medical treatments are limited to short-term use due to risks associated with long-term therapy or insufficient evidence of their prolonged benefits. They find utility in the following scenarios:

• Temporary symptom relief: Used independently to alleviate symptoms temporarily, especially in peri-menopausal women or those unsuitable for surgery due to medical reasons³¹
• Pre-operative aid: Administered before surgery to reduce fibroid size, control bleeding, and facilitate surgical procedures like myomectomy or hysterectomy. Gonadotropin-releasing hormone analogs (GnRHa) are commonly employed for this purpose³¹

Antifibrinolytics Agents (Tranexamic Acid)

Tranexamic acid, used during menstruation, has been linked to a significant reduction in bleeding among women with menorrhagia.³² 

Combined oral contraceptive (COC) and progestins

Physicians often prescribe combined oral contraceptives (COC) to mitigate blood loss associated with uterine fibroids. 

Mirena IUS

The levonorgestrel intrauterine device (LNG-IUS) demonstrates effectiveness in reducing menstrual blood loss and serves as an alternative to surgical treatment.³³

GnRH Analogues (GnRHa)

GnRH analogs, often used with 'add-back therapy', are employed to temporise symptoms in peri-menopausal women or pre-operatively to shrink fibroids and ease surgery.³⁴ They induce fibroid tumour shrinkage by suppressing oestrogen receptor-positive cell growth, altering signal transduction pathways, and inhibiting DNA synthesis.³⁵

Surgical treatments

Endometrial ablation destroys the endometrial lining and can be combined with myomectomy. Hysterectomy with ovarian conservation is an effective option for women not seeking future pregnancies but entails more morbidity. Hysterectomy is the definitive procedure that carries an outstandingly good outcome and guarantees complete cessation of periods with no risk of fibroid recurrence. Hysterectomy can be done via the vaginal, abdominal, or laparoscopic (total or laparoscopic-assisted vaginal) route.²⁷

Fertility considerations

Surgical interventions, such as myomectomy, should be tailored based on fertility desires and fibroid characteristics, with minimally invasive procedures preferred when feasible. However, a complete fertility evaluation is recommended before surgical interventions.²⁷

Summary 

Endometriosis and fibroids typically affect menstruating women. Both conditions are recognized by their severe pelvic pain, heavy menstrual bleeding and limitations in fertility.^36,37 This is due to both conditions promoting growth of unnecessary tissue which disrupts conception.

Fibroids cause the growth of benign tumours in the uterus, while endometriosis causes the growth of endometrial tissue in any part of the reproductive system and even pelvic organs. Tissue of endometrial nature is not considered tumorous since it does not have an invasive and uncontrolled behaviour, which is present in fibrous tissues. Diagnosis of endometriosis can only be confirmed with a non-invasive observation tool via a process called Laparoscopy, and fibroids can be easily diagnosed using ultrasound imaging.^38,39 

Surgical procedures are available for both conditions, though they are not essential. In these interventions, any excess tissue would be removed with the main goal of restoring fertility. Nonetheless, pharmaceutical treatments are widely used to compensate for symptoms and improve quality of life. Most of these are hormonal medications which aim to regulate hormones involved in the menstrual cycle. One of the main differences is that endometriosis is a chronic condition, so even though tissues might be removed, there is a very high recurrence probability. On the other hand, fibroids have a very low recurrence rate. 

Overall, both conditions require a personalised approach to attend to the specific symptoms of each patient and meet their preferences. Understanding the differences can greatly improve the overall quality of life of affected people.