In 2002, the results of the large Women’s Health Initiative (WHI) study have been controversial. As one of the largest clinical trials assessing the safety and efficacy of progesterone on women, the authors of the WHI study concluded that progestin plus estrogen administration can increase one’s risk of developing breast cancer, heart disease, stroke, blood clots, and overall harm, which led to early stoppage of the clinical trial.  However, a large body of clinical trials and other authors do not agree with the results of the WHI study because of the following reasons:
1. The hazard ratio (HR) of the WHI study did not reach statistical significance. Other health experts suggest that the potential health hazards found in the in the estrogen-plus-progestin trial did not reach statistical significance and was based on unadjusted risk hazards. [263-264] In addition, some findings differed for women by age group and years since menopause.
2. The WHI study does not even qualify as a randomized placebo-controlled study.
The reasons for this are the following: [265-269]
a. After randomization, the women were free to decide whether to continue their assigned treatment or whether to undergo diagnostic procedures.
b. Almost 50% of the women were aware of their treatment.
c. The participants received several warnings regarding increased risks of heart disease, stroke and blood clots during the study.
3. The authors of the WHI study did not mention the other significant benefits of estrogen-plus-progestin treatment among the participants. The authors did not mention that the treatment “significantly” decreased the risk of colon cancer and hip fractures (about a 33% reduction) among the participants. 
4. There are some health factors that might have altered the outcome of the WHI study. The participants in the WHI study has an average BMI of 28 (overweight), one-third were hypertensive and one-half were smokers, suggesting that these factors might have significantly altered the outcome of the clinical trial. 
5. The women in the WHI study were 12-15 years past the onset of menopause. This means that the participants were without their premenopausal progesterone levels long enough to bring about various changes in bodily functions.
6. The WHI study actually found beneficial effects of estrogen-plus-progestin on various health hazards. The authors of the WHI study found the following beneficial effects of estrogen-plus-progestin administration: 
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