Table 1 Therapeutic options for medically induced amenorrhea available for female astronauts

Continuous COC

Multiple preparations, tend to be 30–35 μg ethinyl estradiol pill in continuous use

Daily, without pill-free week

Continuous and cyclical use have similar contraceptive efficacy³⁴ with typical use they have a 9% failure rate²⁶

Up to 80% at the end of 1 year of continuous use²⁶

Estrogen and progesterone suppress hormone production and follicle development, endometrium thinner than normal

• Long history and experience with continuous use in spaceflight

• Protect BMD compared with DMPA/non-hormonal contraceptives

• Can be stopped immediately if required

• Decreased risk of ovarian, endometrial, and colorectal cancer, iron deficiency anemia, benign breast disease, functional ovarian cysts, pre-menstrual symptoms, and dysmenorrhea³⁵

• No impact on breast cancer rate

• Daily compliance required—potential issue with worldwide travel and training schedule

• Variable duration of menstrual suppression

• BTB particularly in initial phase

• Hormonal side effects (estrogenic and progestogenic): migraine, VTE, stroke, liver problems, depression, glucose impairment, altered lipid metabolism, and vaginal infections

• Estrogen is contraindicated in some women

• Medication stability problematic on multi-year missions

Progestin-containing intrauterine device

LNG release 20 μg per day, e.g., Mirena (LNG-IUD)

Every 5 years

1-year failure rate is 0.2%⁸

Up to 80% at 1 year of use⁸

62% at 2 years in peri-menopausal women for endometrial protection during HRT use²⁷

LNG downregulates endometrial estrogen and progesterone receptors making endometrium insensitive to circulating estradiol, i.e., strong anti-proliferative effect.

High local drug exposure to the uterine cavity leads to low LNG levels in serum (gradient of endometrium to serum >1,000-fold), leading to minimal systemic side effects³⁶

• Long acting, i.e., no need to remember daily medication

• No effect on BMD in femur and lumbar spine at 2 years³⁷

• Top tier contraceptive efficacy

• Treatment of choice in medical conditions including HMB, iron deficiency anemia, endometrial hyperplasia, endometriosis, adenomyosis, fibroids, and dysmenorrhea³⁵

• Proliferative endometrium much lower in LNG-IUD versus oral progesterone, therefore rate of amenorrhea increased with time³⁸

• Fertility regained after removal

• Can be used in succession for continual benefits

• Discontinuation rates much lower than COC use³⁸

• No upmass or trash to dispose

• Obviates long-duration medication stability issue

• Perforation (rate 1:1,000 insertions up to 9:1,000 insertions.^39–41 Occur mainly in first year of use. May be related to skill of the operator or undetected uterine abnormalities

• Expulsion rate between 2 and 10% in the first year⁴¹

• Infection (0.51% in the first year)⁴²

• Variable duration of initial menstrual suppression due to BTB

• Initial expense

• Insertion-related pain/discomfort

• Hormonal side effects—progesterone related (reduce with time)

Progestin-containing subdermal implant

Etonorgestrel, e.g., Nexplanon

Levonorgestrel, e.g., Jadelle

3 years (Nexplanon) or 5 years (Jadelle)

1-year failure rate is 0.05%⁴¹

Varies between 11% in first 90 days up to 41.25% at 3 years^8,43–45

Inhibits ovulation by suppressing hormone production and follicle development rendering the endometrium thinner than normal (such as COC)⁴⁶

• Long acting with no need to remember daily medication

• No effect on BMD at 2 years compared with non-hormonal contraceptives⁴⁶

• Fertility regained after removal

• Can be used in succession for continual benefits

• No upmass or trash to dispose

• Obviates long-duration medication stability issue

• Subdermal implant may be palpable on arm

• Potential scarring at the site of insertion

• Insertion discomfort

• Variable length of time of menstrual suppression with initial BTB (27–51.25% irregular bleeding pattern)^44,45

• Initial cost

• Hormonal side effects (progesterone related)