Newer Drugs in Medical Management of Uterine Myoma

Fibroids are the most common benign tumours of the female pelvis, with an incidence of 20-30% among women of the reproductive age group. More than 50% of all myomas are asymptomatic. Fibroids are responsible for 2-3% of cases presenting with infertility or subfertility.

Location of Myoma:

Previously, only submucous myomas were thought to affect fertility. Still, a recent meta-analysis showed that intramural myomas not encroaching the endometrial cavity also negatively influence the fertility potential and are associated with significantly lower pregnancy rates.

Size of Myoma: Noncavity distorting intramural myoma affecting fertility was 5cm. But, recently, there have been studies on even smaller fibroids affecting outcomes. The harmful effect on IVF outcome was significant in women with two or more myomas or when the size is more than 3cm.

The possible mechanism for the poor reproductive outcome can be explained by:

1. Altered anatomy- due to the distorted uterine cavity, tubal blockage, or kinking (especially corneal myoma)

2. Altered histology- elongation, and distortion of glands and cystic glandular hyperplasia

3. Altered endometrial and myometrial function- impaired blood supply, increased uterine contractility, and chronic endometrial inflammation

4. Altered autocrine and paracrine mechanisms leading to release of vasoactive amines, cytokines that impair fertility

5. Altered gamete transport potential

Management of fibroid in an infertile patient will depend upon the patient’s age, size, location and send several fibroid-associated symptoms, co-existence, and presence of other infertility factors.

The ideal treatment of uterine myoma should satisfy three goals: -

1. Relief of signs and symptoms

2. Sustained reduction of myoma size

3. Maintenance or improvement of fertility

1.GnRH Agonist

❖ Causes suppression of ovarian steroidogenesis with delayed pituitary downregulation

❖ 30-50% reduction in myoma size and symptoms within 3-6 months

❖ Disadvantages: Medical menopause with symptoms, bone demineralization with long term monotherapy, the requirement of hormonal add-back therapy

❖ Dosage- Leuprolide 3.75mg IM monthly, Goserelin 3.6mg SC monthly, Nafarelin 200mcg intranasal twice daily

2.GnRH Antagonist

❖ Suppression of ovarian steroidogenesis with immediate pituitary downregulation

❖ 25-40% reduction in size and symptoms within three weeks

❖ Hypoestrogenic side effects (vaginal dryness, hot flushes, headache) reduced bone mineral density with prolonged use

❖ Dosage- Cetrorelix 0.25mg SC, Ganirelix 0.25mg SC, (once a week for 8 weeks)

3. Mifepristone

❖ Antiprogesterone effect- reduces action and number of progesterone receptors in myomas

❖ 25-50% decrease in myoma size, 60-70% improvement in symptoms within 3 three months

❖ Disadvantages- Hot flushes, elevated liver enzymes, and endometrial hyperplasia

❖ Dosage- 25-50mg orally daily forthree3 months

4. Selective Progesterone Receptor Modulators

❖ In uterine myoma, Ulipristal acetate induces several desirable changes, including suppression of neovascularisation and cell proliferation, as well as induction of apoptosis

❖ Maintenance of estradiol levels

❖ Decrease by 30-40% in myoma size

❖ Dosage- Ulipristal Acetate 5 mg and Asoprisnil 5-25mg orally daily forthree3 months

5. Raloxifene

❖ Selective Estrogen Receptor Modulators (SERMS)

❖ It decreases myoma size but does not affect uterine bleeding

❖ Disadvantage- Leg cramps, increased risk of DVT and pulmonary embolism

❖ Dosage- 60 mg orally per day

6. Aromatase Inhibitors

❖ Blocks estrogen production

❖ Decrease in myoma size by 60%

❖ Has hypoestrogenic side effects

❖ Dosage- Letrozole 5mg orally per day, Anastrazole 1 mg orally per day for three months

7. Gestrinone

❖ 19 nortestosterone with androgenic,antiprogestrogenic, antiestrogenic and antigonadotropic activity

❖ Causes amenorrhoea in 50-of 100% women

❖ Disadvantages- Weight gain, acne, breast atrophy, oily hair and skin

❖ 1.25-2.5 mg orally twice weekly for six months

8. Da danazol

❖ A synthetic steroid with vigorous antigonadotropic activity

❖ Less effective than GnRH agonist

❖ High risk of weight gain, acne, and other androgenic effects

❖ 200-400 mg twice daily

9 .Cabergoline

❖ Dopamine agonist

❖ A study published in 2007 reported a volume reduction of about 50% in 6 weeks

❖ Dosage- 0.5mg once a week for six weeks

❖ More studies are s required for a definitive conclusion

Vitamin has an antifibrotic factor, inhibits growth, and induces apoptosis in cultured human leiomyoma cells. Pirfenidone affects collagen production and may affect cell growth factors, thereby blocking the growth of existing myoma.

Lanreotide has been shown to reduce growth hormone secretion. Lanreotide induced a 42% mean myoma volume reduction within three months.

Medical therapy is an option if the woman is not considered fit for surgery or does not wish to undergo surgery. However, fibroids will return to pre-therapy within six months of stopping therapy.