Medical Treatment for Endometriosis: Tolerability, Quality of Life and Adherence
Endometriosis, a chronic
inflammatory estrogen-dependent disease characterized by the presence and
proliferation of endometrium outside the uterine cavity.
Endometriosis is associated with
painful symptoms such as chronic pelvic pain, dysmenorrhea and dyspareunia,
infertility, sexological difficulties, and psychological suffering. All these
symptoms have a negative impact on the overall quality of life of women with
endometriosis, including their social and sexual relationships, work and study
productivity, with remarkable social and economic costs
Several medical options are
available to manage symptomatic endometriosis. The pharmacological treatment
for endometriosis-related pain may be necessary for decades, or at least until
there is a desire for pregnancy or physiologic menopause occurs.
In this perspective, clinicians
should consider not only the efficacy, but also side effects, tolerability, and
costs, along with women's preferences toward different treatments.
TAKE HOME MESSAGE:
In this mini-review, authors
analyzed the pros and cons of the available drugs for the medical therapy of
endometriosis, such as estrogen-progestins, progestins, GnRH agonist and GnRH
antagonists.
The medical treatment of
endometriosis can ameliorate painful symptoms of the disease and, consequently,
reduce the negative impact on quality of life and on mental health.
Moreover, pharmacological therapies
for endometriosis prevent pregnancies during their use and do not increase the
likelihood of conception after their discontinuation. Therefore, women should
be informed that medical therapies for endometriosis have no role in case of
infertility.
Thus, medical therapy for
endometriosis should be proposed to women with endometriosis-related pain with
no wish for pregnancy and without surgical indications. Absolute indications
for surgery include the presence of large endometriomas, adnexal masses of
uncertain appearance at diagnostic imaging procedures, ureteral stenosis
causing hydronephrosis, and bowel stenosis associated with sub-occlusive
symptoms.
According to several guidelines on endometriosis-management released by
the most authoritative gynecological societies, hormonal contraceptives,
progestins, anti-progestogens, GnRH agonists, and GnRH antagonists should be
used for the management of endometriosis-related pain.
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GnRH agonists are very effective
for treating endometriosis-associated pain, despite their limited tolerability
and safety.
Side effects, such as hot flushes,
sleep disturbance, and mood swings, are persistent and caused by the severe
hypoestrogenic state induced by these drugs.
In fact, the use of GnRH agonists as a monotherapy, especially in young
women and adolescents, is limited by the unfavorable long-term safety profile,
as well as by the frequency and severity of side effects.
An oral GnRH antagonist (elagolix)
was recently marketed for treating women with endometriosis. The mechanism of
action of elagolix is a dose-dependent suppression of the ovarian estradiol
production, and therefore the induction of a certain degree of hypoestrogenic
state, avoiding the flare-up phase, typically associated with the use of GnRH
agonists.
Elagolix, at the oral daily dose of
150 or 400 mg, was found to determine a reduction in dysmenorrhea of about 46%
in the lower-dose group and 76% in the higher-dose group, as compared to a
menstrual pain reduction of about 23% in the placebo group.
Other GnRH antagonists are
currently being evaluated for the treatment of endometriosis, such as relugolix
and linzagolix.
Combined hormonal contraceptives
have been used for many years as first-line therapy for symptomatic
endometriosis. Estradiol has shown antiapoptotic and inflammatory effects on
ectopic endometrial tissue, whereas progestins have anti-inflammatory and
pro-apoptotic properties.
The combined oral contraceptives
currently in use contain a low level of ethinylestradiol, and have a prevalent
progestin effect on ectopic endometrial tissue.
Estrogen-progestins induce atrophy
of the eutopic and ectopic endometrium, limit retrograde menstruation, inhibit
ovulation, and have anti-inflammatory and proapoptotic effects on endometriotic
foci.
However, one-third of the women with endometriosis do not respond to
estrogen-progestins, which may be in part due to progesterone resistance.
The European Society of Human
Reproduction and Embryology (ESHRE) guidelines on endometriosis pointed out
that, although the evidence on the use of estrogen-progestins for endometriosis
is limited, combined hormonal contraception is extensively used as a treatment
for endometriosis-associated pain.
Progestins (depot
medroxyprogesterone acetate, medroxyprogesterone acetate, norethisterone
acetate, desogestrel and dienogest) can be used as second line treatments.
These compounds could represent a reasonable option in women with endometriosis
who do not respond to estrogen-progestins or in case of deep endometriotic
lesions or in the presence of deep dyspareunia.
Moreover, progestins can be safely
used in women with contraindications to the assumption of estrogens, as well as
in those who do not tolerate estrogens because of their side effects.
In conclusion, when choosing
medical treatments for endometriosis-related pain, clinicians should consider
not only the efficacy, but also side effects, tolerability, adherence to
treatment, costs and women's preferences.
This appears particularly important
if one considers the chronic nature of the disease, potentially determining a
long-term impairment of women's overall quality of life, mental health, social
activities, work, sexual and intimate relationships.
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