What is the role of estrogen and progesterone in treating amenorrhea?

From the Guidelines

Estrogen and progesterone are crucial for treating amenorrhea, with medroxyprogesterone acetate (MPA) being the most effective progestin for inducing secretory endometrium when used with a full replacement dose of estrogen, as evidenced by studies 1. The role of estrogen and progesterone in treating amenorrhea involves addressing the underlying hormonal imbalances that cause absent menstruation. For women with hypothalamic amenorrhea or primary ovarian insufficiency, combined estrogen-progesterone therapy is typically recommended. Some key points to consider when prescribing hormone replacement therapy (HRT) include:

• The choice of progestin, with MPA being the only progestin for which available evidence demonstrates full effectiveness in inducing secretory endometrium together with a full replacement dose of estrogen 1.
• The potential negative impact of MPA on cardiovascular risk, which may be mitigated by the use of natural micronized progesterone (MP) 1.
• The importance of selecting a progestin with a favorable safety profile, such as MP, which has been shown to minimize hormonal-related cardiovascular risks and has a neutral or beneficial effect on blood pressure 1.
• The need to choose between a sequential and continuous regimen of administration, with the latter preventing withdrawal bleeding 1. In terms of specific treatment regimens, combined estrogen-progesterone therapy can be administered in various forms, including:
• Combined oral contraceptives containing ethinyl estradiol and a progestin like norethindrone or levonorgestrel.
• Cyclic hormone therapy with conjugated estrogens or estradiol, adding medroxyprogesterone acetate for the last 10-14 days of the cycle. The goal of treatment is to restore regular withdrawal bleeding, prevent endometrial hyperplasia, and maintain bone density, with estrogen promoting endometrial growth and development, and progesterone stabilizing the endometrium and preventing unopposed estrogen stimulation 1.

From the FDA Drug Label

Medroxyprogesterone acetate, administered parenterally in the recommended doses to women with adequate endogenous estrogen, transforms proliferative endometrium into secretory endometrium. Because of its prolonged action and the resulting difficulty in predicting the time of withdrawal bleeding following injection, medroxyprogesterone acetate is not recommended in secondary amenorrhea or dysfunctional uterine bleeding.

The role of estrogen and progesterone in treating amenorrhea is to:

• Transform proliferative endometrium into secretory endometrium, which is essential for a normal menstrual cycle
• Regulate menstrual bleeding, with estrogen promoting follicular growth and progesterone preparing the uterus for a potential pregnancy However, medroxyprogesterone acetate is not recommended for treating secondary amenorrhea due to its prolonged action and unpredictable withdrawal bleeding 2.

From the Research

Role of Estrogen and Progesterone in Treating Amenorrhea

• Estrogen and progesterone play a crucial role in the treatment of amenorrhea, as they help regulate the menstrual cycle and induce ovulation 3, 4, 5.
• In cases of hypogonadotropic amenorrhea, a sequential use of estrogen and progestogen can be suggested to prevent estrogen deficiency or for psychological reasons 3.
• For women with normogonadotrophic amenorrhea, menstrual bleeding can be induced by cyclical progestogen administration or the sequential use of estrogen plus progestogen 3.
• Low-dose estrogen-progestin therapy has been shown to induce ovulation in selected cases of hypothalamic and ovarian failure 5.
• Cyclical dydrogesterone has been found to be effective in inducing regular withdrawal bleeding in premenopausal women with secondary amenorrhea or oligomenorrhea and normal estrogen levels 6.

Types of Amenorrhea and Treatment

• Primary amenorrhea refers to the absence of menarche at the age of 16, while secondary amenorrhea is the cessation of menses for at least 6 months in already cycling women 3.
• Amenorrhea can be caused by anatomical defects, endocrine dysfunctions, or other factors, and treatment varies depending on the underlying cause 3, 4, 7.
• Hyperprolactinemic amenorrhea is often associated with a pituitary adenoma, and treatment options include prolactin-lowering drugs, cyclical progestogen, and hormone replacement therapy (HRT) 3.
• Hypogonadotropic amenorrhea is frequently associated with stress and nutritional deficiency, and treatment may involve counseling, sequential use of estrogen and progestogen, or ovulation induction with pulsatile gonadotrophin-releasing hormone (GnRH) or gonadotrophins 3, 4, 5.

Benefits and Outcomes of Estrogen and Progesterone Treatment

• Estrogen and progesterone treatment can help regulate the menstrual cycle, induce ovulation, and prevent estrogen deficiency 3, 4, 5.
• Treatment with estrogen and progesterone can also help reduce the risk of endometrial carcinoma and osteoporosis in women with secondary amenorrhea 3, 6.
• In some cases, estrogen and progesterone treatment can help women with amenorrhea conceive, either naturally or through assisted reproductive technology 5, 7.