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

From: Medically induced amenorrhea in female astronauts

Medication Dosing Frequency Contraceptive failure rate Amenorrhea rate Mechanism of action for amenorrhea Advantages Disadvantages
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,​40,​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 years8,43,​44,​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)
  1. Abbreviations: BMD, bone mineral density; BTB, breakthrough bleeding; COC, combined oral contraceptive pill; DMPA, depot medroxyprogesterone acetate injections; HMB, heavy menstrual bleeding; LNG, levonorgestrel; LNG-IUD, levonorgestrel intrauterine device; VTE, venous thromboembolism.